CA2245659A1 - Substituted aromatic phosphonic acid derivatives - Google Patents
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- CA2245659A1 CA2245659A1 CA 2245659 CA2245659A CA2245659A1 CA 2245659 A1 CA2245659 A1 CA 2245659A1 CA 2245659 CA2245659 CA 2245659 CA 2245659 A CA2245659 A CA 2245659A CA 2245659 A1 CA2245659 A1 CA 2245659A1
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Abstract
The invention concerns substituted aromatic phosphonic acid derivatives (I) and their salts, wherein: Eth = 1,2-ethinediyl, an optionally substituted ethane or ethene-1,2-diyl chain; y1 = O, S; y2, y3 = O, S or -N(R6)-; R1, R2, R6, R7 = H, C1-C6-alkyl, C1-C6 alkyl halide, hydroxy-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkoxy halide-C1-C4-alkyl, C3-C4-alkenyloxy-C1-C4-alkyl, C3-C4-alkinyloxy-C1-C4-alkyl, C3-C8-cycloalkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, Di-(C1-C4-alkyl)amino-C1-C4-alkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-alkyl halide-thio-C1-C4-alkyl, C3-C4-alkenylthio-C1-C4-alkyl, C3-C4-alkinylthio-C1-C4-alkyl, C1-C4-alkylsulfinyl-C1-C4-alkyl, C1-C4-alkyl halide sulfinyl-C1-C4-alkyl, C3-C4-alkenylsulfinyl-C1-C4-alkyl, C3-C4-alkinylsulfinyl-C1-C4-alkyl, C1-C4-alkylsulfonyl-C1-C4-alkyl, C1-C4-alkyl halide sulfonyl-C1-C4-alkyl, C3-C4-alkenylsulfonyl-C1-C4-alkyl, C3-C4-alkinylsulfonyl-C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkenyl halide, cyano-C3-C6-alkenyle, C3-C6-alkenyl halide, cyano-C3-C6-alkenyl, C3-C6-alkinyl, C3-C6-alkinyl halide, cyano-C3-C6-alkinyl, hydroxycarbonyl-C1-C4-alkyl, (C1-C4-alkoxy)-carbonyl-C1-C4-alkyl, (C1-C4-alkylthio)carbonyl-C1-C4alkyl, aminocarbonyl-C1-C4-alkyl, (C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, Di-(C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C4-alkyl, phenyl ou phenyl-C1-C4-alkyl optionally substituted 3- to 7-member heterocyclyl or heterocyclyl-C1-C4 alkyl, wherein all the heterocyclenes can optionally contain a carbonyl- or thiocarbonyl ring member; or R1 and R2 and/or R1 and R6 and/or R2 and R7 together are an optionally substituted 1,2-ethanediyl-, 1,3-propylene-, tetramethylene-, pentamethylene or ethyleneoxyethylene chain; or R1 and R2 together are an optionally substituted 1,2-phenylene; R3 = CN, halogen, C1-C4 alkyl, C1-C4 alkyl halide, C1-C4 alkoxy or C1-C4 alkoxy halide; R4 = H, halogen; and R5 = a given heterocyclic ring. The invention further concerns the use of these substances as herbicides and for the desiccation/defoliation of plants.
Description
0050/46586 CA 0224~6~9 1998-08-06 Substituted aromatic phosphonic acid derivatives 5 The present invention relates to novel substituted aromatic phos-phonic acid derivatives of the formula I
R5 yl R4~ Eth - P - y2Rl I
\=~ I
\R3 Y3R2 15 where the variables have the following m~ningS
C. Eth is 1,2-ethynediyl or an ethane- or ethene-1,2-diyl chain,each of which can be unsubstituted or have attached to it one or two of the following substituents: halogen, cyano, carbox-yl, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloal-koxy, (Cl-C4-alkoxy)carbonyl and/or di(Cl-C4-alkyl)amino, it being possible for the ethane-1,2-diyl chain, if desired, additionally to have attached to it a hydroxyl, amino or Cl - C4 - alkyl ~mi no group;
yl is oxygen or sulfur;
y2 is oxygen, sulfur or -N(R6)-;
30 Y3 is oxygen, sulfur or -N(R7)-;
~- Rl, R2, R6 and R7 independently of one another are hydrogen, ~- Cl-C6-alkyl, Cl-C6-haloalkyl, hydroxy-Cl-C4-alkyl, cyano-Cl--C4-alkyl, Cl--C4-alkoxy-Cl--C4--alkyl,Cl--C4--haloalkoxy--Cl-C4-alkyl, C3-C4-alkenyloxy-Cl-C4--alkyl, C3-C4-alkynyloxy-Cl--C4--alkyl,C3--C8--cycloalkoxy--Cl--C4--alkyl,amino--Cl--C4--alkyl, Cl--C4--alkylamino--Cl--C4--alkyl,di(Cl--C4--alkyl)amino--Cl-C4--alkyl, Cl--C4--alkylthio--Cl--C4--alkyl,Cl--C4--haloalkylthio--Cl--C4--alkyl, C3-C4-alkenylthio-Cl-C4-alkyl, C3-C4-alkynylthio-Cl-C4-alkyl, C1-C4-alkylsulfinyl-Cl-C4-alkyl, C1-C4-haloalkylsulfinyl-Cl--C4--alkyl,C3--C4--alkenylsulfinyl--Cl--C4--alkyl,C3--C4--alkynyl--sulfinyl-Cl-C4-alkyl, Cl-C4-alkylsulfonyl-Cl-C4-alkyl, Cl--C4--haloalkylsulfonyl--Cl--C4--alkyl,C3--C4-alkenylsulfonyl--Cl-C4--alkyl, C3--C4--alkynylsulfonyl--Cl--C4--alkyl, C3--C6--alkenyl, C3-C6-haloalkenyl, cyano-C3-C6-alkenyl, C3-C6-alkynyl, C3-C6-haloalkynyl, cyano-C3-C6-alkynyl, hydroxycarbonyl-~ 0050/46586 CA 0224~6~9 1998-08-06 .
Cl-C4-alkyl, (Cl-C4-alkoxy)carbonyl-Cl-C4-alkyl, (Cl-C4-alkyl-thio)carbonyl-Cl-C4-alkyl, aminocarbonyl-Cl-C4-alkyl, (Cl-C4-alkyl)aminocarbonyl-Cl-C4-alkyl, di(Cl-C4-alkyl)amino-carbonyl--Cl--C4--alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-Cl-C4-alkyl, phenyl, phe-nyl-Cl-C4-alkyl or 3- to 7-m~mh~red heterocyclyl or heterocyclyl-Cl-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or th;ocArbonyl ring member, and it being possible for all cycloalkyl, phenyl and het-erocyclyl rings to be unsubstituted or to have attached to .
them one to four substituents, in each case selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, --- carboxyl, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-ha-loalkoxy, Cl-C4-alkylthio, Cl-C4-haloalkylthio, Cl-C4-alkyl-sulfonyl, Cl-C4-haloalkylsulfonyl, (Cl-C4-alkyl)carbonyl, (Cl-C4-haloalkyl)carbonyl, (Cl-C4-alkoxy)carbonyl, (cl-c4-alkyl)carbonyloxy~ (Cl-C4-haloalkyl)carbonyloxy and di(Cl-C4-alkyl)amino, or 25 Rl and R2 or Rl and R6 and/or R2 and R7 in each case together form a 1,2-e~h~ne~;yl, 1,3-propylene, tetramethylene, pentamethy-lene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four Cl-C4-alkyl and/or one or two (Cl-C4-alkoxy)carbonyl groups, or r-Rl and R2 together are 1,2-phenylene which can be unsubstituted or have attached to it one to three substituents, in each case selected from the group consisting of cyano, nitro, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy and Cl-C4-haloal-koxy;
R3 is cyano, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy or Cl-C4-haloalkoxy;
R4 is hydrogen or halogen;
R5 is one of the following heterocycles ~1 to ~20:
~ q~l Rl I R12 ~ N~ o~ N~ N~
R o ~ ~p4 Rl9 R18 R~21 " \ 3~ R2 2_ Z 2 ~ ~6 N ~N
~3 y7 N
O
R28 , ~: ¦ y8 29~N~N~<~9 ~ ~10 ~ N
~=N ~11 ~ ~12 4 5 O~ \ ~ N
0050/46586 CA 02245659 l998-08-06 R35 N ~ ~
R3 ~ ~ ~13 R3~ ~ N ~ ~ ~14 o R40 I R42~ o ~~
~ ~ ~15 o ~ N~ ~16 lS ~ N~o ~ R~S
~ ylO R51 R48 ~ N~ R52 ~ N---- Rso R~9 ~ ~19 ~ ~20 N
O R5 s 23 ~ ~ N
I S ~21 I S ~22 RS ~ 7 N
where 35 R8 is hydrogen, amino, Cl-C4-alkyl or Cl-C4-haloalkyl;
R9 is cyano, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkylsulfonyl or Cl-C4-haloalkylsulfonyl;
40 R10 is Cl-C4-alkyl or Cl-C4-haloalkyl;
Rll is cyano, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkylthio, Cl-C4-haloalkylthio, Cl-C4-alkyl-sulfinyl, Cl-C4-haloalkylsulfinyl, Cl-C4-alkylsulfonyl or Cl-C4-haloalkylsulfonyl, or 0050/46586 CA 0224~6ss 1998-08-06 ._ Rl~ and Rll together with the ring atoms linking them are a 5- to 7 ered heterocycle which has one or two hetero atoms and which can be unsubstituted or have att~ch~A to it one or two C1-C4-alkyl radicals;
R12 is hydrogen, cyano, halogen, C1-C4-alkyl or Cl-C4-haloalkyl;
Y4 is oxygen, sulfur or methylene;
10 R13, R14, R25, R26, R27, R28, R30 and R31 indepen~ntly of one another are hydrogen or Cl-C4-alkyl, or 15 R13 and R14 together with the ring atoms l;nk;ng them are a 5- to 7 ~cred carbo- or heterocyclic ring, it being possible for the ring, if desired, addition-ally to have attached to it one or two halogen and/or Cl-C4-alkyl radicals or a further, fused 3-to 6-membered carbo- or heterocyclic ring;
Rl5 and R16 independently of one another are hydrogen, halogen, Cl-C4-alkyl or C1-C4-haloalkyl, 25 or R15 and R16 together with the ring atoms l;nk;ng them are a 5- to 7-m~mh~ed carbo- or heterocyclic ring which, if desired, can additionally have att~cheA
to it one or two Cl-C4-alkyl r~;c~ls;
,-- R17 is halogen or Cl--C4--alkyl;
R18, R33 and R35 independently of one another are halogen;
35 Rl9, R20, R29, R37, R38, R39, R40, R41, R42, R44, R55 and R57 indepen--dently of one another are hydrogen, Cl-C4-alkyl or Cl--c4--halotalkyl, ,~
40 or Rl9 and R20 and/or R39 and R40 and/or R41 and R42 and/or R55 and R56 s together with the ring atoms l; nk; ng them are a 5--to 7 - b~red ring which, if desired, can addi-tionally have attached to it one or two Cl-C4-alkyl or C1-C4-haloalkyl radicals;
OO50/46586 CA 0224~6~9 1998-08-06 6 ._ y5~ y6~ y7, Y9 and ylO independently of one another are oxygen or sulfur;
zl, z2, z3 and Z4 independently of one another are nitrogen or CH;
R21 and R22 and/or R23 and R24 and/or R53 and R54 together with the ring atoms linking them are a 5- to 7-~~~h~red ring which, if desired, can additionally have attached to it one or two Cl--C4--alkyl rA-l;c~ls;
R32, R34, R48, R49 and R52 independently of one another are hydrogen, Cl-C4-alkyl, C3-C6-cycloalkyl or Cl-C4-ha-loalkyl;
'- y8 is oxygen or =N~;
R36 is hydrogen, Cl-C4-alkyl, Cl-C4-haloalkyl or Cl-C4-haloalkoxy;
R43 iS Cl--C4-alkyl; and R45, R46, R47, R50 and RSl independently of one another are Cl-C4-alkyl, Cl-C4-haloalkyl or C3-C6-cycloalkyl, and the agriculturally useful salts of the compounds I, with the exception of those compounds I where R4 is hydrogen and 30 R5 iS ~2.
~-.
-~ Fur~h~ -~re, the invention relates to - the use of the compounds I as herbicides or for the desicca-tion/defoliation of plants, - herbicidal compositions and compositions for the desiccation/
defoliation of plants which comprise the compounds I as active substances, 40 - processes for the preparation of the compounds I and of herbicidal compositions and compositions for the desiccation~
defoliation of plants using the compounds I, - methods of controlling undesirable vegetation and of desic-. cating/defoliating plants using the compounds I, - -- inte -~ tes of the formulae XXVIII, XXXI, XXXII, XXXIIIa, XXXV and XL and processes for their preparation.
0050/46586 CA 0224~6~9 l998-08-06 7 _ The herbicidal activity of diethyl 1-chloro-2-t2,4-dichlo-ro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-lH-1,2,4-tria-zol-l-yl)phenyl]ethylphosphonate has already been mentioned by G.
Theodoridis, J.T. Bahr, B.L. Davidson, S.E. Hart, F.W. Hotzman, 5 K.M. Poss & S.F. Tutt in ACS Symp. Ser. 584, 90 (1995).
JP 03/151 367 describes 3-phenylpyrazoles of the formula lhalogen]
thalogen] ~ R57 lhalogen]
r/ N
- thaloalkoxy]~
tlower alkyl]
where R57 is, inter alia, ~;~lkoxyphosphinylalkyl as being herbi-cides.
Wo 95/32188 furthermore discloses herbicidally active 3-phenylpy-25 razoles of the formula tCN/CF3/halogen]
~ R59 ~ R58 ~
N
[alkyl/haloalkyl]-tO,S,SO,S02] ~ N\
H/alkyl/haloalkyl where the alkyl/haloalkyl substituents are in each case Cl-C4 and 40 R58 is hydrogen, nitro, halogen, carboxyl or an ester or acid amide radical and R59 is -CH2-CH2-P(o)(OR60)2 or -CH=CH-P(O)(OR6~)2 where R60 =
hydrogen or a specific organic radical.
45 Phenyluracils of the general formula 0050i46586 CA 0224~6~9 1998-08-06 r 8 [inter alia H, alkyl 0,S [H, halogen]
amino]
H, halogen, ~ y unsubst. or subst. alkyl ~ N ~ lhalogen, CN]
H, halogen, ~/ ~ S~ R6 unsubst. or subst. alkyl) ~~~
where the radical R6l is, inter alia, ~iA~ko~y(thio)phosphoryl which is l;nke~ to the aromatic directly or via a chain, come under the general formulae of uracils which - together with other herbicides are suitable for the selective lS control of weeds in rice growing (according to :~~' DE-A 44 37 197);
- are suitable for the semi- and non-selective control of weeds (according to DE-A 44 32 888);
- together with certain other herbicides show a synergistic herbicidal activity (according to DE-A 44 31 219).
US 5 434 2 88 teaches certain benzene derivatives as phospholipase A2 inhibitors. Given a suitable choice of substituents, some of 25 the present compounds I formally also come under the broad definition of these compounds.
Moreover, given a suitable choice of substituents, some compounds of the formula I formally come under the general formulae of 30 - supported catalysts for the preparation of acetic acid which are described in DE-A 41 21 959;
i~- - antithrombic, antiaggregatory and tumor-inhibitory active ingredients which are described in EP-A 537 696 and in DE-A 41 24 942;
35 - active ingredients described in FR-A 2 729 142 as antiarrhythmic substances;
- int~rm~i~tes mentioned in EP-A 421 436 for the preparation of certain NMDA receptor inhibitors.
40 Furthermore, EP-A 426 112 describes photographic silver hAli~e materials which comprise organic phosphorus compounds. These com-pounds, which are very broadly defined, formally also encompass some of the present aromatic phosphonic acid derivatives when the substituents are chosen appropriately.
-0050~46586 CA 0224~6ss 1998-08-06 g ._ Since the herbicidal properties of the abovementioned herbicides are not always entirely satisfactory with regard to the harmful plants, it is an object of the present invention to provide novel herbicidally active compounds with which undesirable plants can S be controlled specifically better than this was possible to date.
The object also extends to providing novel compounds which act as desiccants/defoliants.
We have found that this object is achieved by the present substi-10 tuted aromatic phosphonic acid derivatives of the formula I and by their herbicidal activity.
We have furt~er~ore found herbicidal compositions which comprise 15 the compounds I and which have a very good herbicidal activity.
Moreover, we have found processes for preparing these composi-tions and method of controlling undesirable vegetation using the compounds I.
20 Furthermore, it has been found that the compounds I are also suitable for the desiccation/defoliation of parts of plants, suitable examples being crop plants such as cotton, potatoes, oilseed rape, sunflowers, soybeans or field beans, in particular cotton. Accordingly, we have found compositions for the desicca-25 tion and/or defoliation of plants, processes for the preparationof these compositions, and methods of desiccating and/or defo-liating plants using the compounds I.
Depending on the substitution pattern, the cG..~ounds of the for-30 mula I can contain one or more chiral centers, in which case they exist as enantiomer or diastereomer mixtures. E/Z isomers are ; also possible dep~n~ing on the m~An;ng of Eth. The invention re-lates to the pure enantiomers or the diastereomers and also to mixtures of these.
Agriculturally useful salts are to be understood as ~eAn; ng main-ly the salts of I with those cations and acid addition salts of I
with those acids which do not adversely affect the herbicidal or desiccant/defoliant activity of I.
Thus, suitable cations are, in particular, the ions of the ~1 kAl;
metals, preferably sodium and potassium, of the alkaline earth metals, preferably calcium, magnesium and barium, and of the 45 transition metals, preferably manganese, copper, zinc and iron, and the ammonium ion which may have attached to it a Cl-C4-alkyl, phenyl or benzyl substituent and, if desired, additionally one to three further Cl-C4-alkyl radicals, preferably diisopropylammo-~ 0050/46586 CA 0224~6~9 1998-08-06 ' - ' nium, tetramethylammonium, tetrabutylammonium, trimethylbenzylam-monium, fur~he -re phosphonium ions, preferably tri(Cl-C4-alkyl)-phosphonium, sulfonium ions, preferably tri(Cl-C4-alkyl)-sulfonium, and sulfoxonium ions, preferably tri(Cl-C4-alkyl)-5 sulfoxonium.
Anions of useful acid addition salts are mainly fluoride, chlor-ide, bromide, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, hydrogen carbonate, car-10 bonate, hexafluorosilicate, hexafluorophosphate, benzoate, oxa-late, dodecylbenzenesulfonate, and the anions of Cl-C4-~lk~noic acids, preferably formate, acetate, propionate and buL~late.
15 The organic moieties given for the substituents Rl to R3, R6 to R17, Rl9, R20, R2s to R32, R34, R36 to R52, R5s and R56 or as rA~;c on cycloalkyl, phenyl or heterocyclyl rings or on ethylene, ethene-1,2-diyl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxy ethylene chains are collective terms for individual enumerations of every single group member. All carbon ChA; n~ ~
i.e. all alkyl, haloalkyl, hydroxyalkyl, cyanoalkyl, aminoalkyl, hydroxycarbonyl-alkyl, aminocarbonylalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, halosulfinyl, alkylsul-fonyl, haloalkylsulfonyl, alkylAmino, dialkyl~m;no~ alkenyl, ha-loalkenyl, cyanoalkenyl, alkenyloxy, alkenylthio, alkenylsulfi-nyl, alkenylsulfonyl, alkynyl, haloalkynyl, cyAno~lkynyl, alkyny-loxy, alkynylthio, alkynylsulfinyl and alkynylsulfonyl moieties, can be straight-chain or branched. Halogenated substituents pre-ferably have attached to them one to five identical or different 30 halogen atoms.
f The An;ng halogen is in each case fluorine, bromine, chlorine ~ or iodine, in particular fluorine or chlorine.
35 Other examples of -~n;ngS are:
- Cl - C4 - alkyl is: methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, l-methylpropyl, 2-methylpropyl or l,1-dimethylethyl, in particular methyl or ethyl;
- Cl-C4-haloalkyl is: a Cl-C4-alkyl radical as mentioned above which is partially or fully substituted by fluorine, chlor-ine, bromine and/or iodine, i.e. chloromethyl, dichlorome-thyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluo-romethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodi-fluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chlo-0050/46586 CA 0224~6~9 l998-08-06 ro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichlo-ro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-di-fluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloro-propyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, hepta-fluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chlorome-thyl)-2-chloroethyl, 1-(bL~- ~thyl)-2-bromoethyl, 4-fluo-robutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl, in particular chloromethyl, fluoromethyl, difluoromethyl, tri-fluoromethyl, 2-fluoroethyl, 2-chloroethyl or 2,2,2-trifluo-roethyl;
- Cl-C6-alkyl is: C1-C4-alkyl as mentioned above, and also, for example, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbu-tyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, l,1-dime-thylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpen-tyl, 3-methylpentyl, 4-methylpentyl, l,l-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, l-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl, in particu-lar methyl, ethyl, n-propyl, l-methylethyl, n-butyl, 1,1-dimethylethyl, n-pentyl or n-hexyl;
- Cl-C6-haloalkyl is: a Cl-C6-alkyl radical as mentioned above which is partially or fully substituted by fluorine, chlor-ine, bromine and/or iodine, i.e. one of the radicals men-tioned under Cl-C4-haloalkyl, or 5-fluoro-1-pentyl, 5-chlo-ro-l-pentyl, 5-bromo-1-pentyl, 5-iodo-1-pentyl, 5,5,5-tri-chloro-1-pentyl, undecafluoropentyl, 6-fluoro-1-hexyl, ~- 6-chloro-1-hexyl, 6-bromo-1-hexyl, 6-iodo-1-hexyl, 6,6,6-trichloro-1-hexyl or dodecafluorohexyl, in particular chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl or 2,2,2-trifluoroethyl;
- hydroxy-Cl- C4 - alkyl is: e.g. hydroxymethyl, 2-hydroxyeth-l-yl, 2-hydroxyprop-1-yl, 3-hydroxyprop-1-yl, 1-hydroxyprop-2-yl, 2-hydroxybut-1-yl, 3-hydLoxyLut-1-yl, 4-hydroxybut-1-yl, 1-hydroxybut-2-yl, 1-hydLo~yb~t-3-yl~ 2-hydroxybut-3-yl, 1-hydroxy-2-methylprop-3-yl, 2-hydroxy-2-methylprop-3-yl or 2-hydroxymethylprop-2-yl, in particular 2-hydroxyethyl;
45 - cyano-Cl- C4 - alkyl is: cyanomethyl, 1-cyanoeth-1-yl, 2-cya-noeth-1-yl, 1-cyanoprop-1-yl, 2-cyanoprop-1-yl, 3-cyano-prop-1-yl, 1-cyanoprop-2-yl, 2-cyanoprop-2-yl, 1-cyano-~ 0050~46586 CA 0224~6~9 1998-08-06 ~ . .
but-l-yl, 2-cyanobut-1-yl, 3-cyanobut-1-yl, 4-cyanobut-1-yl, l-cyanobut-2-yl, 2-cyanobut-2-yl, 1-cyanobut-3-yl, 2-cyano-but-3-yl, 1-cyano-2-methylprop-3-yl, 2-cyano-2-methyl-prop-3-yl, 3-cyano-2-methylprop-3-yl or 2-cyano-methylprop-2-yl, in particular cyanomethyl or 2-cyanoethyl;
- amino-Cl-C4-alkyl is: e.g. Amint -Lhyl, 2-aminoethyl, 2-amino-prop-l-yl, 3-aminoprop-1-yl, 2-Aminohut-l-yl, 3-amino-but-l-yl, 4-A~;nohut-l-yl, l-Am;nohut-2-yl, 3-Am;nohut-2-yl, 4-aminobut-2-yl, l-(~-;n~ ~thyl)eth-l-yl, l-(Aminl -thyl)-l-(methyl)eth-l-yl or 1-( A~ inf ~Lhyl)prop-l-yl, in par-ticular ~min~ -thyl or 2-aminoethyl;
hydroxycarbonyl-Cl-C4-alkyl is: hydroxycarbonylmethyl, l-(hy-droxycarbonyl)ethyl, 2-(hydroxycarbonyl)ethyl, l-(hydroxycar-bonyl)prop-l-yl, 2-(hydroxycarbonyl)prop-1-yl, 3-(hydroxycar-bonyl)prop-l-yl, l-(hydroxycarbonyl)but-l-yl, 2-(hydroxycar-bonyl)but-l-yl, 3-(hydroxycarbonyl)but-1-yl, 4-(hydroxycarbo-nyl)but-l-yl, 1-(hydroxycarbonyl)but-2-yl, 2-(hydroxycarbo-nyl)but-2-yl, 3-(hydroxycarbonyl)but-2-yl, 4-(hydroxycarbo-nyl~but-2-yl, l-(hydroxycarbonylmethyl)eth-l-yl, l-(hydroxy-carbonylmethyl)-l-(methyl)eth-l-yl or l-(hydroxycarbonyl-methyl)prop-l-yl, in particular hydroxycarbonylmethyl or 2-(hydroxycarbonyl)ethyl;
- aminocarbonyl-Cl-C4-alkyl is: Aminocarbonylmethyl, l-(amino-carbonyl)ethyl, 2-(aminocarbonyl)ethyl, l-(aminocarbo-nyl)prop-l-yl, 2-(aminocarbonyl)prop-1-yl, 3-(aminocarbo-nyl)prop-l-yl, l-(aminocarbonyl)but-l-yl, 2-(aminocarbo-nyl)but-l-yl, 3-(aminocarbonyl)but-1-yl, 4-(aminocarbo-f~ nyl)but-l-yl, l-(aminocarbonyl)but-2-yl, 2-(aminocarbo-~ nyl)but-2-yl, 3-(aminocarbonyl)but-2-yl, 4-(aminocarbo-nyl)but-2-yl, l-(aminocarbonylmethyl)eth-l-yl, l-(amino-carbonylmethyl)-l-(methyl)eth-l-yl or l-(aminocarbonyl-methyl)prop-l-yl, in particular aminocarbonylmethyl or 2-(aminocarbonyl)ethyl;
- phenyl-Cl-C4-alkyl is: benzyl, l-phenylethyl, 2-phenylethyl, l-phenylprop-l-yl, 2-phenylprop-1-yl, 3-phenylprop-1-yl, l-phenylbut-l-yl, 2-phenylbut-1-yl, 3-phenylbut-1-yl, 4-phe-nylbut-l-yl, l-phenylbut-2-yl, 2-phenylbut-2-yl, 3-phenyl-but-2-yl, 4-phenylbut-2-yl, l-(phenylmethyl)eth-l-yl, l-(phe-nylmethyl)-l-(methyl)eth-l-yl or l-(phenylmethyl)prop-l-yl, in particular benzyl or 2-phenylethyl;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
13 _ - heterocyclyl-Cl-C4-alkyl is: heterocyclylmethyl, 1-heterocy-clylethyl, 2-heterocyclylethyl, 1-heterocyclylprop-1-yl, 2-heterocyclylprop-1-yl, 3-heterocyclylprop-1-yl, 1-heterocy-clylbut-1-yl, 2-heterocyclylbut-1-yl, 4-heterocyclylbut-1-yl, 1-heterocyclylbut-2-yl, 2-heterocyclylbut-2-yl, 3-heterocy-clylbut-2-yl, 3-heterocyclylbut-2-yl, 4-heterocyclylbut-2-yl, l-(heterocyclyl-methyl)eth-1-yl, l-(heterocyclylmethyl)-1-(methyl)eth-1-yl or 1-(heterocyclylmethyl)-prop-1-yl, in particular hetero-cyclylmethyl or 2-heterocyclylethyl or 3-heterocyclylpropyl; in particular 3-oxetanylmethyl, 2-(1,3-oxazolin-2-on-3-yl)ethyl and 3-(2-pyridyl)propyl are especially preferred;
- (Cl-C4-alkyl)carbonyl is: C0-CH3, C0-C2Hs, n-propylcarbonyl, C0-CH(CH3)2, n-butylcarbonyl, l-methylpropylcarbonyl, ~- 2-methylpropylcarbonyl or C0-C(CH3)3, in particular C0-CH3;
- (Cl-C4-haloalkyl)carbonyl is: a (Cl-C4-alkyl)carbonyl rA~;cAl as mentioned above which is partially or fully substituted by fluorine, chlorine, bromine and/or iodine, i.e. chloroacetyl, dichloroacetyl, trichloroacetyl, fluoroacetyl, difluoroace-tyl, C0-CF3, chlorofluoroacetyl, dichlorofluoroacetyl, chlorodifluoroacetyl, 2-fluoroethylcarbonyl, 2-chloroethyl-carbonyl, 2-bromoethylcarbonyl, 2-iodoethylcarbonyl, 2,2-difluoroethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, 2-chloro-2-fluoroethylcarbonyl, 2-chloro-2,2-difluoroethyl-carbonyl, 2,2-~ichloro-2-fluoroethylcarbonyl, 2,2,2-trichlo-roethylcarbonyl, pentafluoroethylcarbonyl, 2-fluoropropylcar-bonyl, 3-fluoropropylcarbonyl, 2,2-difluoropropylcarbonyl, 2,3-difluoropropylcarbonyl, 2-chloropropylcarbonyl, 3-chloro-f propylcarbonyl, 2,3-~ichloropropylcarbonyl, 2-bromopropylcar-~~. bonyl, 3-bromopropylcarbonyl, 3,3,3-trifluoropropylcarbonyl, 3,3,3-trichlol O~LO~Y lcarbonyl, 2,2,3,3,3-pentafluoropropyl-carbonyl, heptafluoropropylcarbonyl, 1-(fluoromethyl)-2-fluo-roethylcarbonyl, 1-(chloromethyl)-2-chloroethylcarbonyl, l-(b,ul.lvl.leLhyl)-2-bromoethylcarbonyl, 4-fluorobutylcarbonyl, 4-chlorobutylcarbonyl, 4-bromobutylcarbonyl or nonafluorobu-tylcarbonyl, in particular C0-CF3;
- (C1-C4-alkyl)carbonyloxy is: acetyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, l-methylethylcarbonyloxy, n-butylcar-bonyloxy, l-methylpropylcarbonyloxy, 2-methylpropylcarbonyl-oxy or l,l-dimethylethylcarbonyloxy, in particular acetyloxy;
~ 0050/46586 CA 0224~6~9 l998-08-06 .
-~ 14 ._ - (Cl-C4-haloalkyl)carbonyloxy is: a (Cl-C4-alkyl)carbonyloxy radical as mentioned above which is partially or fully sub-stituted by fluorine, chlorine, bromine and/or iodine, e.g.
chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, fluo-roacetyloxy, difluoroacetyloxy, trifluoroacetyloxy, chloro-fluoroacetyloxy, dichlorofluoroacetyloxy, chlorodifluoroace-tyloxy, 2-fluoroethylcarbonyloxy, 2-chloroethylcarbonyloxy, 2-bromoethylcarbonyloxy, 2-iodoethylcarbonyloxy, 2,2-difluo-roethylcarbonyloxy, 2,2,2-trifluoroethylcarbonyloxy, 2-chlo-ro-2-fluoroethylcarbonyloxy, 2-chloro-2,2-difluoroethylcar-bonyloxy, 2,2-dichloro-2-fluoroethylcarbonyloxy, 2,2,2-tri-chloroethylcarbonyloxy, pentafluoroethylcarbonyloxy, 2-fluo-Lo~Lopylcarbonyloxy, 3-fluoLo~Lo~ylcarbonyloxy, 2,2-difluoro-propylcarbonyloxy, 2,3-difluoropropylcarbonyloxy, 2-chloro-propylcarbonyloxy, 3-chloropropylcarbonyloxy, 2,3-dichloro-f~ propylcarbonyloxy, 2-bromopropylcarbonyloxy, 3-bromopropyl-'~ carbonyloxy, 3,3,3-trifluolo~o~ylcarbonyloxy, 3,3,3-trichlo-ropropylcarbonyloxy, 2,2,3,3,3-pentafluoropropylcarbonyloxy, heptafluoropropylcarbonyloxy, l-(fluoromethyl)-2-fluoroethyl-carbonyloxy, 1-(chloromethyl)-2-chloroethylcarbonyloxy, l-(bl. ?thyl)-2-bromoethylcarbonyloxy, 4-fluorobutylcar-bonyloxy, 4-chlorobutylcarbonyloxy, 4-bromobutyl or nonafluo-robutyl, in particular trifluoroacetoxy;
25 _ Cl-C4-alkoxy is: methoxy, ethoxy, n-propoxy, l-methylethoxy, n-butoxy, l-methylpropoxy, 2-methylpropoxy or l,l-dimethyl-ethoxy, in particular methoxy or ethoxy;
30 - Cl-C4-h~loAlkoxy is: a Cl-C4-alkoxy rA~;c~l as mentio~e~ above which is partially or fully substituted by fluorine, chlor-. ine, bromine and/or iodine, e.g. chloromethoxy, dichlorome-thoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, tri-fluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bro-moethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoro-ethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, penta-fluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoro-propoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropro-poxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropLo~oxy~
2,2,3,3,3-pentaf 1UOL 0~1 O~OXY, heptafluoropropoxy, l-(fluo-romethyl)-2-fluoroethoxy, 1-(chloromethyl)-2-chloroethoxy, l-(bL~ thyl)-2-bromoethoxy, 4-fluorobutoxy, 4-chlorobu-toxy, 4-bromobutoxy or nonafluorobutoxy, in particular 2-chloroethoxy or 2,2,2-trifluoroethoxy;
0050/46586 CA 0224~6~9 l998-08-06 ~ 15 -- (C1-C4-alkoxy)carbonyl is: CO-OCH3, CO-OC2H5, n-propoxycarbo-~ nyl, CO-OCH(CH3)2, n-butoxycarbonyl, 1-methylpropoxycarbonyl, CO-OCH2-CH(CH3)2 or C0-OC( CH3)3, in particular C0- OCH3 or CO-OC2H5;
- Cl-C6-alkylthio is: SCH3, SC2H5, n-propylthio, SCH(CH3)2, n-butylthio, l-methylpropylthio, 2-methylpropylthio or SC(CH3)3, in particular SCH3 or SC2H5;
-- Cl--C4--alkylaminois: methylamlno, ethyl;~mlno~ n--propylAmino, l-methylethyl~mino~ n-butyl~mino, 1-methylpropylamino, 2-methylpropyl~mino or l,l-dimethylethylamino, in particular methylamino or ethyl~;no;
f - di(Cl-C4-alkyl)amino is: N,N-dimethyl~m;no~ N,N-diethylamino, N,N-dipropylamino, N,N-di(l-methylethyl)amino, N,N-dibutyl-amino, N,N-di(1-methylpropyl)amino, N,N-di(2-methylpro-pyl)amino, N,N-di(1,1-dimethylethyl)amino, N-ethyl-N-methyl-amino, N-methyl-N-propyl~ ;no, N-methyl-N-(l-methyl-ethyl)amino, N-butyl N ...elhyl ~m; no, N-methyl-N-(l-methylpro-pyl)amino, N-methyl-N-(2-methylpropyl)amino, N-(l,l- dime-thylethyl)-N-methyl Am; no, N-ethyl-N-propyl~m;nQ~ N-ethyl-N-(1-methylethyl)amino, N-butyl-N-ethylAm;no, N-ethyl-N-(1-methylpropyl)amino, N-ethyl-N-(2-methylpro-pyl)amino, N-ethyl-N-(1,l-dimethylethyl)amino, N-(l-methyl-ethyl)-N-propyl~m;no~ N-butyl-N-propyl~m; no, N-(1-methylpro-pyl)-N-propyl~;no, N-(2-methylpropyl)-N-propyl~m;no, N-(1,1-dimethylethyl)-N-propyl Am; no, N-butyl-N-(1-methyl-ethyl)amino, N-(1-methylethyl)-N-(1-methylpropyl)amino, N-(1-methylethyl)-N-(2-methylpropyl)amino, N-(1,1-dimethyl-f- ethyl)-N-(l-methylethyl)amino, N-butyl-N-(l-methylpro-' pyl)amino, N-butyl-N-(2-methylpropyl)amino, N-butyl-N-(l,1-dimethylethyl)amino, N-(l-methylpropyl)-N-(2-methyl-propyl)amino, N-(l,1-dimethylethyl)-N-(1-methylpropyl)amino or N-(l,l-dimethylethyl)-N-(2-methylpropyl)amino, in particu-lar N,N-dimethyl~m;no or N,N-diethyl~mino;
- Cl-C4-alkoxy-Cl-C4-alkyl is: Cl-C4-alkyl substituted by Cl-C4-alkoxy as mentioned above, e.g. methoxymethyl, ethoxyme-thyl, n-propoxymethyl, (l-methylethoxy)methyl, n-butoxyme-thyl, (l-methylpropoxy)methyl, (2-methylpropoxy)methyl, (l,l-dimethylethoxy)methyl, 2-(methoxy)ethyl, 2-(ethoxy)ethyl, 2-(n-propoxy)ethyl, 2-(l-methylethoxy)ethyl, 2-(n-butoxy)ethyl, 2-(l-methylpropoxy)ethyl, 2-(2-methylpro-poxy)ethyl, 2-(1,1-dimethylethoxy)ethyl, 2-(methoxy)propyl, 2-(ethoxy)propyl, 2-(n-propoxy)propyl, 2-(1-methylethoxy)pro-.
0050/46586 CA 0224~6~9 l998-08-06 pyl, 2-(n-butoxy)propyl, 2-(l-methylpLo~oxy)propyl~
2-(2-methylpropoxy)propyl, 2-(1,1-dimethylethoxy)propyl, 3-(methoxy)propyl, 3-(ethoxy)propyl, 3-(n-propoxy)propyl, 3~ methylethoxy)propyl, 3-(n-butoxy)propyl, 3-(1-methylpro-S poxy)propyl, 3-(2-methylpropoxy)propyl, 3-(1,1-dimethyl-ethoxy)propyl, 2-(methoxy)butyl, 2-(ethoxy)butyl, 2-(n-pro-poxy)butyl, 2-(1-methylethoxy)butyl, 2-(n-butoxy)butyl, 2-(1-methylpropoxy)butyl, 2-(2-methylpLo~oxy)butyl~
2-(1,1-dimethylethoxy)butyl, 3-(methoxy)butyl, 3-(ethoxy)butyl, 3-(n-pLo~o~y)butyl, 3-(l-methylethoxy)butyl, 3-(n-butoxy)butyl~ 3-(1-methylpropoxy)butyl, 3-(2-methylpro-poxy)butyl, 3-(1,1-dimethylethoxy)butyl, 4-(methoxy)butyl, 4-(ethoxy)butyl, 4-(n-propoxy)butyl, 4-(1-methylethoxy)butyl, 4-(n-butoxy)butyl, 4-(1-methylpropoxy)butyl, 4-(2-methylpro-poxy)butyl or 4-(1,1-dimethylethoxy)butyl, in particular me-thoxyl..e~hyl or 2-methoxyethyl;
, .
-- (Cl--C4--alkoxy)carbonyl--Cl--C4--alkylis: Cl--C4--alkylsubstituted by (cl-c4-alkoxy)carbonyl as mentioned above, e.g. methoxycar-bonylmethyl, ethoxycarbonylmethyl, l-(methoxycarbonyl)ethyl or 2-(methoxycarbonyl)ethyl;
- Cl-C4-alkylthio-Cl-C4-alkyl is: Cl-C4-alkyl substituted by Cl-C4-alkylthio as mentioned above, e.g. methylthiomethyl, ethylth;~ -thyl, n-propylth;o~thyl~ (l-methylethyl-thio)methyl, n-butylth;om?thyl, (l-methylpropylthio)methyl, (2-methylpropylthio)methyl, (l,l-dimethylethylthio)methyl, 2-methylthioethyl, 2-ethylthioethyl, 2-(n-propylthio)ethyl, 2-(1-methylethylthio)ethyl, 2-(n-butylthio)ethyl, 2-(1-methyl-propylthio)ethyl, 2-(2-methylpropylthio)ethyl, 2-(1,l-dimethylethylthio)ethyl, 2-(methylthio)propyl, 3-(me-thylthio)propyl, 2-(ethylthio)propyl, 3-(ethylthio)propyl, 3-(propylthio)propyl, 3-(butylthio)propyl, 4-(methyl-thio)butyl, 4-(ethylthio)butyl, 4-(n-propylthio)butyl or 4-(n-butylthio)butyl, in particular 2-(methylthio)ethyl;
- (Cl-C4-alkylthio)carbonyl-Cl-C4-alkyl is: Cl-C4-alkyl substi-tuted by (Cl-C4-alkylthio)carbonyl, such as (methylthio)carbo-nyl, (ethylthio)carbonyl, (n-propylthio)carbonyl, (l-methyl-ethylthio)carbonyl, (n-butylthio)carbonyl, (l-methylpropyl-thio)carbonyl, (2-methylpropylthio)carbonyl and (l,l-dime-thylethylthio)carbonyl, preferably (methylthio)carbonyl or (ethylthio)carbonyl, e.g. (methylthio)carbonylmethyl, (ethyl-thio)carbonylmethyl, l-tmethylthio)carbonyllethyl or 2-[(me-thylthio)carbonyl]ethyl;
0050/4b586 CA 0224~6~9 1998-08-06 17 _ - C1-C4-haloalkylthio-Cl-C4-alkyl is: Cl-C4-alkyl as mentioned above which has att~che~ to it a Cl-C4-alkylthio group which is partially or fully substituted by fluorine, chlorine and/
or bromine, e.g. difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, bromodifluoromethylthio, 2-fluoro-ethylthio, 2-chloroethylthio, 2-bromoethylthio, 2-iodoethyl-thio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2,2,2-trichloroethylthio, 2-chloro-2-fluoroethylthio, 2-chlo-ro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, pentafluoroethylthio, 2-fluoropropylthio, 3-fluoropropylthio, 2-chloropropylthio, 3-chloropropylthio, 2-bromopropylthio, 3-bromopropylthio, 2,2-difluoropropylthio, 2,3-difluoropro-pylthio, 2,3-dichloropropylthio, 3,3,3-trifluoropropylthio, 3,3,3-trichloropropylthio, 2,2,3,3,3-pentafluoropropylthio, heptafluoropropylthio, 1-(fluoromethyl)-2-fluoroethylthio, ,-- 1-(chloromethyl)-2-chloroethylthio, l-(b L o.. J~-ethyl)-2-bromo-ethylthio, 4-fluorobutylthio, 4-chlorobutylthio or 4-bromobu-tylthio, e.g. difluoromethylthiomethyl;
20 _ C1-C4-alkylamino-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by Cl-C4-alkylamino as mentioned above, e.g. methylami-nomethyl, ethyl~mi n- ~ thyl, n-propylAmin~m~thyl~ (1-methyl-ethyl~m;no)methyl, n-butyl~m;n,- ?thyl, (l-methylpropylami-no)methyl, (2-methylpropylamino)methyl, (1,1-dimethylethyl-amino)methyl, 2-methylaminoethyl, 2-ethyl~m;noethyl, 2-(n-propyl~m;no)ethyl, 2-(1-methylethylamino)ethyl, 2-(n-butyl ~m; nO ) ethyl, 2-(1-methylpropyl ~m; nO ) ethyl, 2-(2-me-thylpropylamino)ethyl, 2-(1,1-dimethylethyl~m i no ) ethyl, 2-(methylA~ino)propyl, 3-(methylAm;no)propyl, 2-(ethylami-no)propyl, 3-(ethyl~mino)propyl~ 3-(propyl~m;no)propyl, 3-(butyl~m; no ) propyl, 4-(methyl~m;no)butyl, 4-(ethylami-no)butyl, 4-(n-propyl~m; no ) butyl or 4-(n-butylamino)butyl, in particular 2-(methyl~m; no ) ethyl;
- Cl-C4-alkyl ~m; nocarbonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by Cl-C4-alkylaminocarbonyl, such as methyl~ in~-carbonyl, ethylaminocarbonyl, n-propyl~minocarbonyl, 1-me-thylethylaminocarbonyl, n-butyl~minocarbonyl, l-methylpropyl-aminocarbonyl, 2-methylpropyl~;nocarbonyl or 1,1-dimethyl-ethyl ~m; nocarbonyl, preferably methylaminocarbonyl or ethyl-aminocarbonyl, e.g. (methylaminocarbonyl)methyl, (ethylamino-carbonyl)methyl, l-(methyl~minocarbonyl)ethyl or 2-(methyl-aminocarbonyl)ethyl;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
- di-(Cl-C4-alkyl)amino-Cl-C4-alkyl: Cl-C4-alkyl which is sub-stituted by di(Cl-C4-alkyl)amino as mentioned abo~e, e.g.
dimethylaminomethyl or diethyl~m;nf-?thyl;
R5 yl R4~ Eth - P - y2Rl I
\=~ I
\R3 Y3R2 15 where the variables have the following m~ningS
C. Eth is 1,2-ethynediyl or an ethane- or ethene-1,2-diyl chain,each of which can be unsubstituted or have attached to it one or two of the following substituents: halogen, cyano, carbox-yl, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloal-koxy, (Cl-C4-alkoxy)carbonyl and/or di(Cl-C4-alkyl)amino, it being possible for the ethane-1,2-diyl chain, if desired, additionally to have attached to it a hydroxyl, amino or Cl - C4 - alkyl ~mi no group;
yl is oxygen or sulfur;
y2 is oxygen, sulfur or -N(R6)-;
30 Y3 is oxygen, sulfur or -N(R7)-;
~- Rl, R2, R6 and R7 independently of one another are hydrogen, ~- Cl-C6-alkyl, Cl-C6-haloalkyl, hydroxy-Cl-C4-alkyl, cyano-Cl--C4-alkyl, Cl--C4-alkoxy-Cl--C4--alkyl,Cl--C4--haloalkoxy--Cl-C4-alkyl, C3-C4-alkenyloxy-Cl-C4--alkyl, C3-C4-alkynyloxy-Cl--C4--alkyl,C3--C8--cycloalkoxy--Cl--C4--alkyl,amino--Cl--C4--alkyl, Cl--C4--alkylamino--Cl--C4--alkyl,di(Cl--C4--alkyl)amino--Cl-C4--alkyl, Cl--C4--alkylthio--Cl--C4--alkyl,Cl--C4--haloalkylthio--Cl--C4--alkyl, C3-C4-alkenylthio-Cl-C4-alkyl, C3-C4-alkynylthio-Cl-C4-alkyl, C1-C4-alkylsulfinyl-Cl-C4-alkyl, C1-C4-haloalkylsulfinyl-Cl--C4--alkyl,C3--C4--alkenylsulfinyl--Cl--C4--alkyl,C3--C4--alkynyl--sulfinyl-Cl-C4-alkyl, Cl-C4-alkylsulfonyl-Cl-C4-alkyl, Cl--C4--haloalkylsulfonyl--Cl--C4--alkyl,C3--C4-alkenylsulfonyl--Cl-C4--alkyl, C3--C4--alkynylsulfonyl--Cl--C4--alkyl, C3--C6--alkenyl, C3-C6-haloalkenyl, cyano-C3-C6-alkenyl, C3-C6-alkynyl, C3-C6-haloalkynyl, cyano-C3-C6-alkynyl, hydroxycarbonyl-~ 0050/46586 CA 0224~6~9 1998-08-06 .
Cl-C4-alkyl, (Cl-C4-alkoxy)carbonyl-Cl-C4-alkyl, (Cl-C4-alkyl-thio)carbonyl-Cl-C4-alkyl, aminocarbonyl-Cl-C4-alkyl, (Cl-C4-alkyl)aminocarbonyl-Cl-C4-alkyl, di(Cl-C4-alkyl)amino-carbonyl--Cl--C4--alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-Cl-C4-alkyl, phenyl, phe-nyl-Cl-C4-alkyl or 3- to 7-m~mh~red heterocyclyl or heterocyclyl-Cl-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or th;ocArbonyl ring member, and it being possible for all cycloalkyl, phenyl and het-erocyclyl rings to be unsubstituted or to have attached to .
them one to four substituents, in each case selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, --- carboxyl, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-ha-loalkoxy, Cl-C4-alkylthio, Cl-C4-haloalkylthio, Cl-C4-alkyl-sulfonyl, Cl-C4-haloalkylsulfonyl, (Cl-C4-alkyl)carbonyl, (Cl-C4-haloalkyl)carbonyl, (Cl-C4-alkoxy)carbonyl, (cl-c4-alkyl)carbonyloxy~ (Cl-C4-haloalkyl)carbonyloxy and di(Cl-C4-alkyl)amino, or 25 Rl and R2 or Rl and R6 and/or R2 and R7 in each case together form a 1,2-e~h~ne~;yl, 1,3-propylene, tetramethylene, pentamethy-lene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four Cl-C4-alkyl and/or one or two (Cl-C4-alkoxy)carbonyl groups, or r-Rl and R2 together are 1,2-phenylene which can be unsubstituted or have attached to it one to three substituents, in each case selected from the group consisting of cyano, nitro, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy and Cl-C4-haloal-koxy;
R3 is cyano, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy or Cl-C4-haloalkoxy;
R4 is hydrogen or halogen;
R5 is one of the following heterocycles ~1 to ~20:
~ q~l Rl I R12 ~ N~ o~ N~ N~
R o ~ ~p4 Rl9 R18 R~21 " \ 3~ R2 2_ Z 2 ~ ~6 N ~N
~3 y7 N
O
R28 , ~: ¦ y8 29~N~N~<~9 ~ ~10 ~ N
~=N ~11 ~ ~12 4 5 O~ \ ~ N
0050/46586 CA 02245659 l998-08-06 R35 N ~ ~
R3 ~ ~ ~13 R3~ ~ N ~ ~ ~14 o R40 I R42~ o ~~
~ ~ ~15 o ~ N~ ~16 lS ~ N~o ~ R~S
~ ylO R51 R48 ~ N~ R52 ~ N---- Rso R~9 ~ ~19 ~ ~20 N
O R5 s 23 ~ ~ N
I S ~21 I S ~22 RS ~ 7 N
where 35 R8 is hydrogen, amino, Cl-C4-alkyl or Cl-C4-haloalkyl;
R9 is cyano, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkylsulfonyl or Cl-C4-haloalkylsulfonyl;
40 R10 is Cl-C4-alkyl or Cl-C4-haloalkyl;
Rll is cyano, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkylthio, Cl-C4-haloalkylthio, Cl-C4-alkyl-sulfinyl, Cl-C4-haloalkylsulfinyl, Cl-C4-alkylsulfonyl or Cl-C4-haloalkylsulfonyl, or 0050/46586 CA 0224~6ss 1998-08-06 ._ Rl~ and Rll together with the ring atoms linking them are a 5- to 7 ered heterocycle which has one or two hetero atoms and which can be unsubstituted or have att~ch~A to it one or two C1-C4-alkyl radicals;
R12 is hydrogen, cyano, halogen, C1-C4-alkyl or Cl-C4-haloalkyl;
Y4 is oxygen, sulfur or methylene;
10 R13, R14, R25, R26, R27, R28, R30 and R31 indepen~ntly of one another are hydrogen or Cl-C4-alkyl, or 15 R13 and R14 together with the ring atoms l;nk;ng them are a 5- to 7 ~cred carbo- or heterocyclic ring, it being possible for the ring, if desired, addition-ally to have attached to it one or two halogen and/or Cl-C4-alkyl radicals or a further, fused 3-to 6-membered carbo- or heterocyclic ring;
Rl5 and R16 independently of one another are hydrogen, halogen, Cl-C4-alkyl or C1-C4-haloalkyl, 25 or R15 and R16 together with the ring atoms l;nk;ng them are a 5- to 7-m~mh~ed carbo- or heterocyclic ring which, if desired, can additionally have att~cheA
to it one or two Cl-C4-alkyl r~;c~ls;
,-- R17 is halogen or Cl--C4--alkyl;
R18, R33 and R35 independently of one another are halogen;
35 Rl9, R20, R29, R37, R38, R39, R40, R41, R42, R44, R55 and R57 indepen--dently of one another are hydrogen, Cl-C4-alkyl or Cl--c4--halotalkyl, ,~
40 or Rl9 and R20 and/or R39 and R40 and/or R41 and R42 and/or R55 and R56 s together with the ring atoms l; nk; ng them are a 5--to 7 - b~red ring which, if desired, can addi-tionally have attached to it one or two Cl-C4-alkyl or C1-C4-haloalkyl radicals;
OO50/46586 CA 0224~6~9 1998-08-06 6 ._ y5~ y6~ y7, Y9 and ylO independently of one another are oxygen or sulfur;
zl, z2, z3 and Z4 independently of one another are nitrogen or CH;
R21 and R22 and/or R23 and R24 and/or R53 and R54 together with the ring atoms linking them are a 5- to 7-~~~h~red ring which, if desired, can additionally have attached to it one or two Cl--C4--alkyl rA-l;c~ls;
R32, R34, R48, R49 and R52 independently of one another are hydrogen, Cl-C4-alkyl, C3-C6-cycloalkyl or Cl-C4-ha-loalkyl;
'- y8 is oxygen or =N~;
R36 is hydrogen, Cl-C4-alkyl, Cl-C4-haloalkyl or Cl-C4-haloalkoxy;
R43 iS Cl--C4-alkyl; and R45, R46, R47, R50 and RSl independently of one another are Cl-C4-alkyl, Cl-C4-haloalkyl or C3-C6-cycloalkyl, and the agriculturally useful salts of the compounds I, with the exception of those compounds I where R4 is hydrogen and 30 R5 iS ~2.
~-.
-~ Fur~h~ -~re, the invention relates to - the use of the compounds I as herbicides or for the desicca-tion/defoliation of plants, - herbicidal compositions and compositions for the desiccation/
defoliation of plants which comprise the compounds I as active substances, 40 - processes for the preparation of the compounds I and of herbicidal compositions and compositions for the desiccation~
defoliation of plants using the compounds I, - methods of controlling undesirable vegetation and of desic-. cating/defoliating plants using the compounds I, - -- inte -~ tes of the formulae XXVIII, XXXI, XXXII, XXXIIIa, XXXV and XL and processes for their preparation.
0050/46586 CA 0224~6~9 l998-08-06 7 _ The herbicidal activity of diethyl 1-chloro-2-t2,4-dichlo-ro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-lH-1,2,4-tria-zol-l-yl)phenyl]ethylphosphonate has already been mentioned by G.
Theodoridis, J.T. Bahr, B.L. Davidson, S.E. Hart, F.W. Hotzman, 5 K.M. Poss & S.F. Tutt in ACS Symp. Ser. 584, 90 (1995).
JP 03/151 367 describes 3-phenylpyrazoles of the formula lhalogen]
thalogen] ~ R57 lhalogen]
r/ N
- thaloalkoxy]~
tlower alkyl]
where R57 is, inter alia, ~;~lkoxyphosphinylalkyl as being herbi-cides.
Wo 95/32188 furthermore discloses herbicidally active 3-phenylpy-25 razoles of the formula tCN/CF3/halogen]
~ R59 ~ R58 ~
N
[alkyl/haloalkyl]-tO,S,SO,S02] ~ N\
H/alkyl/haloalkyl where the alkyl/haloalkyl substituents are in each case Cl-C4 and 40 R58 is hydrogen, nitro, halogen, carboxyl or an ester or acid amide radical and R59 is -CH2-CH2-P(o)(OR60)2 or -CH=CH-P(O)(OR6~)2 where R60 =
hydrogen or a specific organic radical.
45 Phenyluracils of the general formula 0050i46586 CA 0224~6~9 1998-08-06 r 8 [inter alia H, alkyl 0,S [H, halogen]
amino]
H, halogen, ~ y unsubst. or subst. alkyl ~ N ~ lhalogen, CN]
H, halogen, ~/ ~ S~ R6 unsubst. or subst. alkyl) ~~~
where the radical R6l is, inter alia, ~iA~ko~y(thio)phosphoryl which is l;nke~ to the aromatic directly or via a chain, come under the general formulae of uracils which - together with other herbicides are suitable for the selective lS control of weeds in rice growing (according to :~~' DE-A 44 37 197);
- are suitable for the semi- and non-selective control of weeds (according to DE-A 44 32 888);
- together with certain other herbicides show a synergistic herbicidal activity (according to DE-A 44 31 219).
US 5 434 2 88 teaches certain benzene derivatives as phospholipase A2 inhibitors. Given a suitable choice of substituents, some of 25 the present compounds I formally also come under the broad definition of these compounds.
Moreover, given a suitable choice of substituents, some compounds of the formula I formally come under the general formulae of 30 - supported catalysts for the preparation of acetic acid which are described in DE-A 41 21 959;
i~- - antithrombic, antiaggregatory and tumor-inhibitory active ingredients which are described in EP-A 537 696 and in DE-A 41 24 942;
35 - active ingredients described in FR-A 2 729 142 as antiarrhythmic substances;
- int~rm~i~tes mentioned in EP-A 421 436 for the preparation of certain NMDA receptor inhibitors.
40 Furthermore, EP-A 426 112 describes photographic silver hAli~e materials which comprise organic phosphorus compounds. These com-pounds, which are very broadly defined, formally also encompass some of the present aromatic phosphonic acid derivatives when the substituents are chosen appropriately.
-0050~46586 CA 0224~6ss 1998-08-06 g ._ Since the herbicidal properties of the abovementioned herbicides are not always entirely satisfactory with regard to the harmful plants, it is an object of the present invention to provide novel herbicidally active compounds with which undesirable plants can S be controlled specifically better than this was possible to date.
The object also extends to providing novel compounds which act as desiccants/defoliants.
We have found that this object is achieved by the present substi-10 tuted aromatic phosphonic acid derivatives of the formula I and by their herbicidal activity.
We have furt~er~ore found herbicidal compositions which comprise 15 the compounds I and which have a very good herbicidal activity.
Moreover, we have found processes for preparing these composi-tions and method of controlling undesirable vegetation using the compounds I.
20 Furthermore, it has been found that the compounds I are also suitable for the desiccation/defoliation of parts of plants, suitable examples being crop plants such as cotton, potatoes, oilseed rape, sunflowers, soybeans or field beans, in particular cotton. Accordingly, we have found compositions for the desicca-25 tion and/or defoliation of plants, processes for the preparationof these compositions, and methods of desiccating and/or defo-liating plants using the compounds I.
Depending on the substitution pattern, the cG..~ounds of the for-30 mula I can contain one or more chiral centers, in which case they exist as enantiomer or diastereomer mixtures. E/Z isomers are ; also possible dep~n~ing on the m~An;ng of Eth. The invention re-lates to the pure enantiomers or the diastereomers and also to mixtures of these.
Agriculturally useful salts are to be understood as ~eAn; ng main-ly the salts of I with those cations and acid addition salts of I
with those acids which do not adversely affect the herbicidal or desiccant/defoliant activity of I.
Thus, suitable cations are, in particular, the ions of the ~1 kAl;
metals, preferably sodium and potassium, of the alkaline earth metals, preferably calcium, magnesium and barium, and of the 45 transition metals, preferably manganese, copper, zinc and iron, and the ammonium ion which may have attached to it a Cl-C4-alkyl, phenyl or benzyl substituent and, if desired, additionally one to three further Cl-C4-alkyl radicals, preferably diisopropylammo-~ 0050/46586 CA 0224~6~9 1998-08-06 ' - ' nium, tetramethylammonium, tetrabutylammonium, trimethylbenzylam-monium, fur~he -re phosphonium ions, preferably tri(Cl-C4-alkyl)-phosphonium, sulfonium ions, preferably tri(Cl-C4-alkyl)-sulfonium, and sulfoxonium ions, preferably tri(Cl-C4-alkyl)-5 sulfoxonium.
Anions of useful acid addition salts are mainly fluoride, chlor-ide, bromide, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, hydrogen carbonate, car-10 bonate, hexafluorosilicate, hexafluorophosphate, benzoate, oxa-late, dodecylbenzenesulfonate, and the anions of Cl-C4-~lk~noic acids, preferably formate, acetate, propionate and buL~late.
15 The organic moieties given for the substituents Rl to R3, R6 to R17, Rl9, R20, R2s to R32, R34, R36 to R52, R5s and R56 or as rA~;c on cycloalkyl, phenyl or heterocyclyl rings or on ethylene, ethene-1,2-diyl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxy ethylene chains are collective terms for individual enumerations of every single group member. All carbon ChA; n~ ~
i.e. all alkyl, haloalkyl, hydroxyalkyl, cyanoalkyl, aminoalkyl, hydroxycarbonyl-alkyl, aminocarbonylalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, halosulfinyl, alkylsul-fonyl, haloalkylsulfonyl, alkylAmino, dialkyl~m;no~ alkenyl, ha-loalkenyl, cyanoalkenyl, alkenyloxy, alkenylthio, alkenylsulfi-nyl, alkenylsulfonyl, alkynyl, haloalkynyl, cyAno~lkynyl, alkyny-loxy, alkynylthio, alkynylsulfinyl and alkynylsulfonyl moieties, can be straight-chain or branched. Halogenated substituents pre-ferably have attached to them one to five identical or different 30 halogen atoms.
f The An;ng halogen is in each case fluorine, bromine, chlorine ~ or iodine, in particular fluorine or chlorine.
35 Other examples of -~n;ngS are:
- Cl - C4 - alkyl is: methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, l-methylpropyl, 2-methylpropyl or l,1-dimethylethyl, in particular methyl or ethyl;
- Cl-C4-haloalkyl is: a Cl-C4-alkyl radical as mentioned above which is partially or fully substituted by fluorine, chlor-ine, bromine and/or iodine, i.e. chloromethyl, dichlorome-thyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluo-romethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodi-fluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chlo-0050/46586 CA 0224~6~9 l998-08-06 ro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichlo-ro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-di-fluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloro-propyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, hepta-fluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chlorome-thyl)-2-chloroethyl, 1-(bL~- ~thyl)-2-bromoethyl, 4-fluo-robutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl, in particular chloromethyl, fluoromethyl, difluoromethyl, tri-fluoromethyl, 2-fluoroethyl, 2-chloroethyl or 2,2,2-trifluo-roethyl;
- Cl-C6-alkyl is: C1-C4-alkyl as mentioned above, and also, for example, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbu-tyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, l,1-dime-thylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpen-tyl, 3-methylpentyl, 4-methylpentyl, l,l-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, l-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl, in particu-lar methyl, ethyl, n-propyl, l-methylethyl, n-butyl, 1,1-dimethylethyl, n-pentyl or n-hexyl;
- Cl-C6-haloalkyl is: a Cl-C6-alkyl radical as mentioned above which is partially or fully substituted by fluorine, chlor-ine, bromine and/or iodine, i.e. one of the radicals men-tioned under Cl-C4-haloalkyl, or 5-fluoro-1-pentyl, 5-chlo-ro-l-pentyl, 5-bromo-1-pentyl, 5-iodo-1-pentyl, 5,5,5-tri-chloro-1-pentyl, undecafluoropentyl, 6-fluoro-1-hexyl, ~- 6-chloro-1-hexyl, 6-bromo-1-hexyl, 6-iodo-1-hexyl, 6,6,6-trichloro-1-hexyl or dodecafluorohexyl, in particular chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl or 2,2,2-trifluoroethyl;
- hydroxy-Cl- C4 - alkyl is: e.g. hydroxymethyl, 2-hydroxyeth-l-yl, 2-hydroxyprop-1-yl, 3-hydroxyprop-1-yl, 1-hydroxyprop-2-yl, 2-hydroxybut-1-yl, 3-hydLoxyLut-1-yl, 4-hydroxybut-1-yl, 1-hydroxybut-2-yl, 1-hydLo~yb~t-3-yl~ 2-hydroxybut-3-yl, 1-hydroxy-2-methylprop-3-yl, 2-hydroxy-2-methylprop-3-yl or 2-hydroxymethylprop-2-yl, in particular 2-hydroxyethyl;
45 - cyano-Cl- C4 - alkyl is: cyanomethyl, 1-cyanoeth-1-yl, 2-cya-noeth-1-yl, 1-cyanoprop-1-yl, 2-cyanoprop-1-yl, 3-cyano-prop-1-yl, 1-cyanoprop-2-yl, 2-cyanoprop-2-yl, 1-cyano-~ 0050~46586 CA 0224~6~9 1998-08-06 ~ . .
but-l-yl, 2-cyanobut-1-yl, 3-cyanobut-1-yl, 4-cyanobut-1-yl, l-cyanobut-2-yl, 2-cyanobut-2-yl, 1-cyanobut-3-yl, 2-cyano-but-3-yl, 1-cyano-2-methylprop-3-yl, 2-cyano-2-methyl-prop-3-yl, 3-cyano-2-methylprop-3-yl or 2-cyano-methylprop-2-yl, in particular cyanomethyl or 2-cyanoethyl;
- amino-Cl-C4-alkyl is: e.g. Amint -Lhyl, 2-aminoethyl, 2-amino-prop-l-yl, 3-aminoprop-1-yl, 2-Aminohut-l-yl, 3-amino-but-l-yl, 4-A~;nohut-l-yl, l-Am;nohut-2-yl, 3-Am;nohut-2-yl, 4-aminobut-2-yl, l-(~-;n~ ~thyl)eth-l-yl, l-(Aminl -thyl)-l-(methyl)eth-l-yl or 1-( A~ inf ~Lhyl)prop-l-yl, in par-ticular ~min~ -thyl or 2-aminoethyl;
hydroxycarbonyl-Cl-C4-alkyl is: hydroxycarbonylmethyl, l-(hy-droxycarbonyl)ethyl, 2-(hydroxycarbonyl)ethyl, l-(hydroxycar-bonyl)prop-l-yl, 2-(hydroxycarbonyl)prop-1-yl, 3-(hydroxycar-bonyl)prop-l-yl, l-(hydroxycarbonyl)but-l-yl, 2-(hydroxycar-bonyl)but-l-yl, 3-(hydroxycarbonyl)but-1-yl, 4-(hydroxycarbo-nyl)but-l-yl, 1-(hydroxycarbonyl)but-2-yl, 2-(hydroxycarbo-nyl)but-2-yl, 3-(hydroxycarbonyl)but-2-yl, 4-(hydroxycarbo-nyl~but-2-yl, l-(hydroxycarbonylmethyl)eth-l-yl, l-(hydroxy-carbonylmethyl)-l-(methyl)eth-l-yl or l-(hydroxycarbonyl-methyl)prop-l-yl, in particular hydroxycarbonylmethyl or 2-(hydroxycarbonyl)ethyl;
- aminocarbonyl-Cl-C4-alkyl is: Aminocarbonylmethyl, l-(amino-carbonyl)ethyl, 2-(aminocarbonyl)ethyl, l-(aminocarbo-nyl)prop-l-yl, 2-(aminocarbonyl)prop-1-yl, 3-(aminocarbo-nyl)prop-l-yl, l-(aminocarbonyl)but-l-yl, 2-(aminocarbo-nyl)but-l-yl, 3-(aminocarbonyl)but-1-yl, 4-(aminocarbo-f~ nyl)but-l-yl, l-(aminocarbonyl)but-2-yl, 2-(aminocarbo-~ nyl)but-2-yl, 3-(aminocarbonyl)but-2-yl, 4-(aminocarbo-nyl)but-2-yl, l-(aminocarbonylmethyl)eth-l-yl, l-(amino-carbonylmethyl)-l-(methyl)eth-l-yl or l-(aminocarbonyl-methyl)prop-l-yl, in particular aminocarbonylmethyl or 2-(aminocarbonyl)ethyl;
- phenyl-Cl-C4-alkyl is: benzyl, l-phenylethyl, 2-phenylethyl, l-phenylprop-l-yl, 2-phenylprop-1-yl, 3-phenylprop-1-yl, l-phenylbut-l-yl, 2-phenylbut-1-yl, 3-phenylbut-1-yl, 4-phe-nylbut-l-yl, l-phenylbut-2-yl, 2-phenylbut-2-yl, 3-phenyl-but-2-yl, 4-phenylbut-2-yl, l-(phenylmethyl)eth-l-yl, l-(phe-nylmethyl)-l-(methyl)eth-l-yl or l-(phenylmethyl)prop-l-yl, in particular benzyl or 2-phenylethyl;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
13 _ - heterocyclyl-Cl-C4-alkyl is: heterocyclylmethyl, 1-heterocy-clylethyl, 2-heterocyclylethyl, 1-heterocyclylprop-1-yl, 2-heterocyclylprop-1-yl, 3-heterocyclylprop-1-yl, 1-heterocy-clylbut-1-yl, 2-heterocyclylbut-1-yl, 4-heterocyclylbut-1-yl, 1-heterocyclylbut-2-yl, 2-heterocyclylbut-2-yl, 3-heterocy-clylbut-2-yl, 3-heterocyclylbut-2-yl, 4-heterocyclylbut-2-yl, l-(heterocyclyl-methyl)eth-1-yl, l-(heterocyclylmethyl)-1-(methyl)eth-1-yl or 1-(heterocyclylmethyl)-prop-1-yl, in particular hetero-cyclylmethyl or 2-heterocyclylethyl or 3-heterocyclylpropyl; in particular 3-oxetanylmethyl, 2-(1,3-oxazolin-2-on-3-yl)ethyl and 3-(2-pyridyl)propyl are especially preferred;
- (Cl-C4-alkyl)carbonyl is: C0-CH3, C0-C2Hs, n-propylcarbonyl, C0-CH(CH3)2, n-butylcarbonyl, l-methylpropylcarbonyl, ~- 2-methylpropylcarbonyl or C0-C(CH3)3, in particular C0-CH3;
- (Cl-C4-haloalkyl)carbonyl is: a (Cl-C4-alkyl)carbonyl rA~;cAl as mentioned above which is partially or fully substituted by fluorine, chlorine, bromine and/or iodine, i.e. chloroacetyl, dichloroacetyl, trichloroacetyl, fluoroacetyl, difluoroace-tyl, C0-CF3, chlorofluoroacetyl, dichlorofluoroacetyl, chlorodifluoroacetyl, 2-fluoroethylcarbonyl, 2-chloroethyl-carbonyl, 2-bromoethylcarbonyl, 2-iodoethylcarbonyl, 2,2-difluoroethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, 2-chloro-2-fluoroethylcarbonyl, 2-chloro-2,2-difluoroethyl-carbonyl, 2,2-~ichloro-2-fluoroethylcarbonyl, 2,2,2-trichlo-roethylcarbonyl, pentafluoroethylcarbonyl, 2-fluoropropylcar-bonyl, 3-fluoropropylcarbonyl, 2,2-difluoropropylcarbonyl, 2,3-difluoropropylcarbonyl, 2-chloropropylcarbonyl, 3-chloro-f propylcarbonyl, 2,3-~ichloropropylcarbonyl, 2-bromopropylcar-~~. bonyl, 3-bromopropylcarbonyl, 3,3,3-trifluoropropylcarbonyl, 3,3,3-trichlol O~LO~Y lcarbonyl, 2,2,3,3,3-pentafluoropropyl-carbonyl, heptafluoropropylcarbonyl, 1-(fluoromethyl)-2-fluo-roethylcarbonyl, 1-(chloromethyl)-2-chloroethylcarbonyl, l-(b,ul.lvl.leLhyl)-2-bromoethylcarbonyl, 4-fluorobutylcarbonyl, 4-chlorobutylcarbonyl, 4-bromobutylcarbonyl or nonafluorobu-tylcarbonyl, in particular C0-CF3;
- (C1-C4-alkyl)carbonyloxy is: acetyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, l-methylethylcarbonyloxy, n-butylcar-bonyloxy, l-methylpropylcarbonyloxy, 2-methylpropylcarbonyl-oxy or l,l-dimethylethylcarbonyloxy, in particular acetyloxy;
~ 0050/46586 CA 0224~6~9 l998-08-06 .
-~ 14 ._ - (Cl-C4-haloalkyl)carbonyloxy is: a (Cl-C4-alkyl)carbonyloxy radical as mentioned above which is partially or fully sub-stituted by fluorine, chlorine, bromine and/or iodine, e.g.
chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, fluo-roacetyloxy, difluoroacetyloxy, trifluoroacetyloxy, chloro-fluoroacetyloxy, dichlorofluoroacetyloxy, chlorodifluoroace-tyloxy, 2-fluoroethylcarbonyloxy, 2-chloroethylcarbonyloxy, 2-bromoethylcarbonyloxy, 2-iodoethylcarbonyloxy, 2,2-difluo-roethylcarbonyloxy, 2,2,2-trifluoroethylcarbonyloxy, 2-chlo-ro-2-fluoroethylcarbonyloxy, 2-chloro-2,2-difluoroethylcar-bonyloxy, 2,2-dichloro-2-fluoroethylcarbonyloxy, 2,2,2-tri-chloroethylcarbonyloxy, pentafluoroethylcarbonyloxy, 2-fluo-Lo~Lopylcarbonyloxy, 3-fluoLo~Lo~ylcarbonyloxy, 2,2-difluoro-propylcarbonyloxy, 2,3-difluoropropylcarbonyloxy, 2-chloro-propylcarbonyloxy, 3-chloropropylcarbonyloxy, 2,3-dichloro-f~ propylcarbonyloxy, 2-bromopropylcarbonyloxy, 3-bromopropyl-'~ carbonyloxy, 3,3,3-trifluolo~o~ylcarbonyloxy, 3,3,3-trichlo-ropropylcarbonyloxy, 2,2,3,3,3-pentafluoropropylcarbonyloxy, heptafluoropropylcarbonyloxy, l-(fluoromethyl)-2-fluoroethyl-carbonyloxy, 1-(chloromethyl)-2-chloroethylcarbonyloxy, l-(bl. ?thyl)-2-bromoethylcarbonyloxy, 4-fluorobutylcar-bonyloxy, 4-chlorobutylcarbonyloxy, 4-bromobutyl or nonafluo-robutyl, in particular trifluoroacetoxy;
25 _ Cl-C4-alkoxy is: methoxy, ethoxy, n-propoxy, l-methylethoxy, n-butoxy, l-methylpropoxy, 2-methylpropoxy or l,l-dimethyl-ethoxy, in particular methoxy or ethoxy;
30 - Cl-C4-h~loAlkoxy is: a Cl-C4-alkoxy rA~;c~l as mentio~e~ above which is partially or fully substituted by fluorine, chlor-. ine, bromine and/or iodine, e.g. chloromethoxy, dichlorome-thoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, tri-fluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bro-moethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoro-ethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, penta-fluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoro-propoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropro-poxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropLo~oxy~
2,2,3,3,3-pentaf 1UOL 0~1 O~OXY, heptafluoropropoxy, l-(fluo-romethyl)-2-fluoroethoxy, 1-(chloromethyl)-2-chloroethoxy, l-(bL~ thyl)-2-bromoethoxy, 4-fluorobutoxy, 4-chlorobu-toxy, 4-bromobutoxy or nonafluorobutoxy, in particular 2-chloroethoxy or 2,2,2-trifluoroethoxy;
0050/46586 CA 0224~6~9 l998-08-06 ~ 15 -- (C1-C4-alkoxy)carbonyl is: CO-OCH3, CO-OC2H5, n-propoxycarbo-~ nyl, CO-OCH(CH3)2, n-butoxycarbonyl, 1-methylpropoxycarbonyl, CO-OCH2-CH(CH3)2 or C0-OC( CH3)3, in particular C0- OCH3 or CO-OC2H5;
- Cl-C6-alkylthio is: SCH3, SC2H5, n-propylthio, SCH(CH3)2, n-butylthio, l-methylpropylthio, 2-methylpropylthio or SC(CH3)3, in particular SCH3 or SC2H5;
-- Cl--C4--alkylaminois: methylamlno, ethyl;~mlno~ n--propylAmino, l-methylethyl~mino~ n-butyl~mino, 1-methylpropylamino, 2-methylpropyl~mino or l,l-dimethylethylamino, in particular methylamino or ethyl~;no;
f - di(Cl-C4-alkyl)amino is: N,N-dimethyl~m;no~ N,N-diethylamino, N,N-dipropylamino, N,N-di(l-methylethyl)amino, N,N-dibutyl-amino, N,N-di(1-methylpropyl)amino, N,N-di(2-methylpro-pyl)amino, N,N-di(1,1-dimethylethyl)amino, N-ethyl-N-methyl-amino, N-methyl-N-propyl~ ;no, N-methyl-N-(l-methyl-ethyl)amino, N-butyl N ...elhyl ~m; no, N-methyl-N-(l-methylpro-pyl)amino, N-methyl-N-(2-methylpropyl)amino, N-(l,l- dime-thylethyl)-N-methyl Am; no, N-ethyl-N-propyl~m;nQ~ N-ethyl-N-(1-methylethyl)amino, N-butyl-N-ethylAm;no, N-ethyl-N-(1-methylpropyl)amino, N-ethyl-N-(2-methylpro-pyl)amino, N-ethyl-N-(1,l-dimethylethyl)amino, N-(l-methyl-ethyl)-N-propyl~m;no~ N-butyl-N-propyl~m; no, N-(1-methylpro-pyl)-N-propyl~;no, N-(2-methylpropyl)-N-propyl~m;no, N-(1,1-dimethylethyl)-N-propyl Am; no, N-butyl-N-(1-methyl-ethyl)amino, N-(1-methylethyl)-N-(1-methylpropyl)amino, N-(1-methylethyl)-N-(2-methylpropyl)amino, N-(1,1-dimethyl-f- ethyl)-N-(l-methylethyl)amino, N-butyl-N-(l-methylpro-' pyl)amino, N-butyl-N-(2-methylpropyl)amino, N-butyl-N-(l,1-dimethylethyl)amino, N-(l-methylpropyl)-N-(2-methyl-propyl)amino, N-(l,1-dimethylethyl)-N-(1-methylpropyl)amino or N-(l,l-dimethylethyl)-N-(2-methylpropyl)amino, in particu-lar N,N-dimethyl~m;no or N,N-diethyl~mino;
- Cl-C4-alkoxy-Cl-C4-alkyl is: Cl-C4-alkyl substituted by Cl-C4-alkoxy as mentioned above, e.g. methoxymethyl, ethoxyme-thyl, n-propoxymethyl, (l-methylethoxy)methyl, n-butoxyme-thyl, (l-methylpropoxy)methyl, (2-methylpropoxy)methyl, (l,l-dimethylethoxy)methyl, 2-(methoxy)ethyl, 2-(ethoxy)ethyl, 2-(n-propoxy)ethyl, 2-(l-methylethoxy)ethyl, 2-(n-butoxy)ethyl, 2-(l-methylpropoxy)ethyl, 2-(2-methylpro-poxy)ethyl, 2-(1,1-dimethylethoxy)ethyl, 2-(methoxy)propyl, 2-(ethoxy)propyl, 2-(n-propoxy)propyl, 2-(1-methylethoxy)pro-.
0050/46586 CA 0224~6~9 l998-08-06 pyl, 2-(n-butoxy)propyl, 2-(l-methylpLo~oxy)propyl~
2-(2-methylpropoxy)propyl, 2-(1,1-dimethylethoxy)propyl, 3-(methoxy)propyl, 3-(ethoxy)propyl, 3-(n-propoxy)propyl, 3~ methylethoxy)propyl, 3-(n-butoxy)propyl, 3-(1-methylpro-S poxy)propyl, 3-(2-methylpropoxy)propyl, 3-(1,1-dimethyl-ethoxy)propyl, 2-(methoxy)butyl, 2-(ethoxy)butyl, 2-(n-pro-poxy)butyl, 2-(1-methylethoxy)butyl, 2-(n-butoxy)butyl, 2-(1-methylpropoxy)butyl, 2-(2-methylpLo~oxy)butyl~
2-(1,1-dimethylethoxy)butyl, 3-(methoxy)butyl, 3-(ethoxy)butyl, 3-(n-pLo~o~y)butyl, 3-(l-methylethoxy)butyl, 3-(n-butoxy)butyl~ 3-(1-methylpropoxy)butyl, 3-(2-methylpro-poxy)butyl, 3-(1,1-dimethylethoxy)butyl, 4-(methoxy)butyl, 4-(ethoxy)butyl, 4-(n-propoxy)butyl, 4-(1-methylethoxy)butyl, 4-(n-butoxy)butyl, 4-(1-methylpropoxy)butyl, 4-(2-methylpro-poxy)butyl or 4-(1,1-dimethylethoxy)butyl, in particular me-thoxyl..e~hyl or 2-methoxyethyl;
, .
-- (Cl--C4--alkoxy)carbonyl--Cl--C4--alkylis: Cl--C4--alkylsubstituted by (cl-c4-alkoxy)carbonyl as mentioned above, e.g. methoxycar-bonylmethyl, ethoxycarbonylmethyl, l-(methoxycarbonyl)ethyl or 2-(methoxycarbonyl)ethyl;
- Cl-C4-alkylthio-Cl-C4-alkyl is: Cl-C4-alkyl substituted by Cl-C4-alkylthio as mentioned above, e.g. methylthiomethyl, ethylth;~ -thyl, n-propylth;o~thyl~ (l-methylethyl-thio)methyl, n-butylth;om?thyl, (l-methylpropylthio)methyl, (2-methylpropylthio)methyl, (l,l-dimethylethylthio)methyl, 2-methylthioethyl, 2-ethylthioethyl, 2-(n-propylthio)ethyl, 2-(1-methylethylthio)ethyl, 2-(n-butylthio)ethyl, 2-(1-methyl-propylthio)ethyl, 2-(2-methylpropylthio)ethyl, 2-(1,l-dimethylethylthio)ethyl, 2-(methylthio)propyl, 3-(me-thylthio)propyl, 2-(ethylthio)propyl, 3-(ethylthio)propyl, 3-(propylthio)propyl, 3-(butylthio)propyl, 4-(methyl-thio)butyl, 4-(ethylthio)butyl, 4-(n-propylthio)butyl or 4-(n-butylthio)butyl, in particular 2-(methylthio)ethyl;
- (Cl-C4-alkylthio)carbonyl-Cl-C4-alkyl is: Cl-C4-alkyl substi-tuted by (Cl-C4-alkylthio)carbonyl, such as (methylthio)carbo-nyl, (ethylthio)carbonyl, (n-propylthio)carbonyl, (l-methyl-ethylthio)carbonyl, (n-butylthio)carbonyl, (l-methylpropyl-thio)carbonyl, (2-methylpropylthio)carbonyl and (l,l-dime-thylethylthio)carbonyl, preferably (methylthio)carbonyl or (ethylthio)carbonyl, e.g. (methylthio)carbonylmethyl, (ethyl-thio)carbonylmethyl, l-tmethylthio)carbonyllethyl or 2-[(me-thylthio)carbonyl]ethyl;
0050/4b586 CA 0224~6~9 1998-08-06 17 _ - C1-C4-haloalkylthio-Cl-C4-alkyl is: Cl-C4-alkyl as mentioned above which has att~che~ to it a Cl-C4-alkylthio group which is partially or fully substituted by fluorine, chlorine and/
or bromine, e.g. difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, bromodifluoromethylthio, 2-fluoro-ethylthio, 2-chloroethylthio, 2-bromoethylthio, 2-iodoethyl-thio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2,2,2-trichloroethylthio, 2-chloro-2-fluoroethylthio, 2-chlo-ro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, pentafluoroethylthio, 2-fluoropropylthio, 3-fluoropropylthio, 2-chloropropylthio, 3-chloropropylthio, 2-bromopropylthio, 3-bromopropylthio, 2,2-difluoropropylthio, 2,3-difluoropro-pylthio, 2,3-dichloropropylthio, 3,3,3-trifluoropropylthio, 3,3,3-trichloropropylthio, 2,2,3,3,3-pentafluoropropylthio, heptafluoropropylthio, 1-(fluoromethyl)-2-fluoroethylthio, ,-- 1-(chloromethyl)-2-chloroethylthio, l-(b L o.. J~-ethyl)-2-bromo-ethylthio, 4-fluorobutylthio, 4-chlorobutylthio or 4-bromobu-tylthio, e.g. difluoromethylthiomethyl;
20 _ C1-C4-alkylamino-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by Cl-C4-alkylamino as mentioned above, e.g. methylami-nomethyl, ethyl~mi n- ~ thyl, n-propylAmin~m~thyl~ (1-methyl-ethyl~m;no)methyl, n-butyl~m;n,- ?thyl, (l-methylpropylami-no)methyl, (2-methylpropylamino)methyl, (1,1-dimethylethyl-amino)methyl, 2-methylaminoethyl, 2-ethyl~m;noethyl, 2-(n-propyl~m;no)ethyl, 2-(1-methylethylamino)ethyl, 2-(n-butyl ~m; nO ) ethyl, 2-(1-methylpropyl ~m; nO ) ethyl, 2-(2-me-thylpropylamino)ethyl, 2-(1,1-dimethylethyl~m i no ) ethyl, 2-(methylA~ino)propyl, 3-(methylAm;no)propyl, 2-(ethylami-no)propyl, 3-(ethyl~mino)propyl~ 3-(propyl~m;no)propyl, 3-(butyl~m; no ) propyl, 4-(methyl~m;no)butyl, 4-(ethylami-no)butyl, 4-(n-propyl~m; no ) butyl or 4-(n-butylamino)butyl, in particular 2-(methyl~m; no ) ethyl;
- Cl-C4-alkyl ~m; nocarbonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by Cl-C4-alkylaminocarbonyl, such as methyl~ in~-carbonyl, ethylaminocarbonyl, n-propyl~minocarbonyl, 1-me-thylethylaminocarbonyl, n-butyl~minocarbonyl, l-methylpropyl-aminocarbonyl, 2-methylpropyl~;nocarbonyl or 1,1-dimethyl-ethyl ~m; nocarbonyl, preferably methylaminocarbonyl or ethyl-aminocarbonyl, e.g. (methylaminocarbonyl)methyl, (ethylamino-carbonyl)methyl, l-(methyl~minocarbonyl)ethyl or 2-(methyl-aminocarbonyl)ethyl;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
- di-(Cl-C4-alkyl)amino-Cl-C4-alkyl: Cl-C4-alkyl which is sub-stituted by di(Cl-C4-alkyl)amino as mentioned abo~e, e.g.
dimethylaminomethyl or diethyl~m;nf-?thyl;
5 - di(Cl-C4-alkyl)aminocarbonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by di(Cl-C4-alkyl)aminocarbonyl, such as N,N-dimethylAm;nocarbonyl~ N,N-diethyl~m;nocarbonyl, N,N-di-propylaminocarbonyl, N,N-di(l-methylethyl)aminocarbonyl, N,N-dibutyl A~ inocarbonyl, N,N-di(l-methylpropyl)aminocarbo-nyl, N,N-di(2-methylpropyl)aminocarbonyl, N,N-di(l,l-dime-thylethyl)aminocarbonyl, N-ethyl-N-methyl Am; nocarbonyl, N-methyl-N-propylAminocarbonyl~ N-methyl-N-(l-methyl-ethyl)aminocarbonyl, N-butyl N ~Lhyl ~m; nocarbonyl, N-methyl-N-(l-methylpropyl)aminocarbonyl, N-methyl-N-(2-methyl-propyl)A~;nocArbonyl, N-(l,l-dimethylethyl) N ...eLhylA~;nocAr-r-. bonyl, N-ethyl-N-propylA~;nocarbonyl, N-ethyl-N-(l-methyl-ethyl)aminocarbonyl, N-butyl-N-ethyl ;nocarbonyl, N-ethyl-N-(l-methylpropyl)~m;nocarbonyl, N-ethyl-N-(2-methyl-propyl)aminocarbonyl, N-ethyl-N-(l,l-dimethylethyl)aminocar-bonyl, N-(l-methylethyl)-N-propylaminocarbonyl, N-butyl-N-propylAm;nocarbonyl, N-(l-methylpropyl)-N-propyl~minocarbo-nyl, N-(2-methylpropyl)-N-propyl A~; noc~rbonyl, N-(l,l-dime-thylethyl)-N-propyl~m;n~carbor.yl, N-butyl-N-(l-.m2thyl-ethyl)aminocarbonyl, N-(l-methylethyl)-N-(l-methylpropyl)ami-nocarbonyl, N-(l-methylethyl)-N-(2-methylpropyl)aminocarbo-nyl, N-(l,l-dimethylethyl)-N-(l-methylethyl)aminocarbonyl, N-butyl-N-(l-methylpropyl)aminocarbonyl, N-butyl-N-(2-methyl-propyl)aminocarbonyl, N-butyl-N-(l,l-dimethylethyl)aminocar-bonyl, N-(l-methylpropyl)-N-(2-methylpropyl)aminocarbonyl, N-(l,l-dimethylethyl)-N-(l-methylpropyl)aminocarbonyl or N-(l,l-dimethylethyl)-N-(2-methylpropyl)aminocarbonyl, pre-ferably N,N-dimethylAm;nocarbonyl or N,N-diethylAm;nocarb nyl, e.g. dimethylAminocarbonylmethyl~ diethylAm;nocarbo-nylmethyl, l-(dimethy~m;nocarbonyl)ethyl or 2-(dimethylami-nocarbonyl)ethyl;
- Cl-C4-alkylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, l-methylethylsulfinyl, n-butylsulfinyl, l-methylpropylsulfi-nyl, 2-methylpropylsulfinyl or l,l-dimethylethylsulfinyl, preferably methylsulfinyl, for example methylsulfinylmethyl or 2-methylsulfinylethyl;
45 - Cl-C4-haloalkylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl as men-tioned above which has attached to it a Cl-C4-alkylsulfinyl group which is partially or fully substituted by fluorine, ~ 0050/46586 CA 0224~6~9 1998-08-06 chlorine and/or bromine, e.g. difluoromethylsulfinyl, tri-fluoromethylsulfinyl, chlorodifluoromethylsulfinyl, bromodi-fluoromethylsulfinyl, 2-fluoroethylsulfinyl, 2-chloroethyl-sulfinyl, 2-bromoethylsulfinyl, 2-iodoethylsulfinyl, 2,2-di-fluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl, 2,2,2-trichloroethylsulfinyl, 2-chloro-2-fluoroethylsulfinyl, 2-chloro-2,2-difluoroethylsulfinyl, 2,2-dichloro-2-fluoro-ethylsulfinyl, pentafluoroethylsulfinyl, 2-fluoropropylsulfi-nyl, 3-fluoropropylsulfinyl, 2-chloropropylsulfinyl, 3-chlo-ropropylsulfinyl, 2-bromopropylsulfinyl, 3-bromopropylsulfi-nyl, 2,2-difluolopLopylsulfinyl, 2,3-difluoropropylsulfinyl, 2,3-dichloropropylsulfinyl, 3,3,3-trifluoropropylsulfinyl, 3,3,3-trichloropropylsulfinyl, 2,2,3,3,3-pentafluoropropyl-sulfinyl, heptafluoro~lopylsulfinyl, l-(fluoromethyl)-2-fluo-roethylsulfinyl, 1-(chloromethyl)-2-chloroethylsulfinyl, - 1-(bl~"lor"eLhyl)-2-bromoethylsulfinyl, 4-fluorobutylsulfinyl, 4-chlorobutylsulfinyl or 4-bromobutylsulfinyl, for example difluoromethylsulfinylmethyl;
20 _ Cl-C4-alkylsulfonyl is: S02-CH3, S02-C2H5, n-propylsulfonyl, S02-CH(CH3)2, n-butylsulfonyl, l-methylpropylsulfonyl, 2-methylpropylsulfonyl or S02-C(CH3), in particular S02-CH3 or S02-C2H5;
- C1-C4-alkylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by Cl-C4-alkylsulfonyl as mentioned above, preferably methylsulfonyl, for example methylsulfonylmethyl or 2-methyl-sulfonylethyl;
- Cl-C4-haloalkylsulfohyl-Cl-C4-alkyl is: Cl-C4-alkyl as men-'- tioned above which has attached to it a Cl-C4-alkylsulfonyl ' group which is partially or fully substituted by fluorine, chlorine and/or bromine, e.g. difluoromethylsulfonyl, tri-fluoromethylsulfonyl, chlorodifluoromethylsulfonyl, bl~
fluoromethylsulfonyl, 2-fluoroethylsulfonyl, 2-chloroethyl-sulfonyl, 2-bromoethylsulfonyl, 2-iodoethylsulfonyl, 2,2-di-fluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, 2,2,2-trichloroethylsulfonyl, 2-chloro-2-fluoroethylsulfonyl, 2-chloro-2,2-difluoroethylsulfonyl, 2,2-dichloro-2-fluoro-ethylsulfonyl, pentafluoroethylsulfonyl, 2-fluoropropylsulfo-nyl, 3-fluoropropylsulfonyl, 2-chloropropylsulfonyl, 3-chlo-ropropylsulfonyl, 2-bromopropylsulfonyl, 3-bromopropylsulfo-nyl, 2,2-difluoropropylsulfonyl, 2,3-difluoropropylsulfonyl, 2,3-dichloropropylsulfonyl, 3,3,3-trifluoropropylsulfonyl, 3,3,3-trichloropropylsulfonyl, 2,2,3,3,3-pentafluoropropyl-sulfonyl, heptafluoropropylsulfonyl, l-(fluoromethyl)-2-fluo-0050/46586 CA 0224~6~9 l998-08-06 ~ . .
. 20 ~-roethylsulfonyl, l-(chloromethyl)-2-chloroethylsulfonyl, l-(b~ -Lhyl)-2-bromoethylsulfonyl, 4-fluorobutylsulfonyl, 4-chlorobutylsulfonyl or 4-bromobutylsulfonyl, for example 2-chloroethylsulfonyl;
- C3-C6-alkenyl is: e.g. prop-2-en-1-yl, n-buten-4-yl, l-methyl-prop-2-en-1-yl, 2-methylprop-2-en-1-yl, 2-buten-1-yl, n-penten-3-yl, n-penten-4-yl, 1-methylbut-2-en-1-yl, 2-me-thylbut-2-en-1-yl, 3-methylbut-2-en-l-yl, l-methyl-but-3-en-1-yl, 2-methylbut-3-en-1-yl, 3-methylbut-3-en-1-yl, 1,1-dimethylprop-2-en-l-yl, 1,2-dimethylprop-2-en-1-yl, 1-ethylprop-2-en-1-yl, n-hex-3-en-1-yl, n-hex-4-en-l-yl, n-hex-5-en-1-yl, 1-methylpent-3-en-1-yl, 2-methyl-pent-3-en-1-yl, 3-methylpent-3-en-1-yl, 4-methyl-pent-3-en-1-yl, 1-methylpent-4-en-1-yl, 2-methyl-~ pent-4-en-1-yl, 3-methylpent-4-en-1-yl, 4-methyl-'- pent-4-en-1-yl, 1,1-dimethylbut-2-en-1-yl, l,l-dimethyl-but-3-en-1-yl, 1,2-dimethylbut-2-en-1-yl, 1,2-dimethyl-but-3-en-l-yl, 1,3-dimethylbut-2-en-l-yl, 1,3-dimethyl-but-3-en-l-yl, 2,2-dimethylbut-3-en-1-yl, 2,3-dimethyl-but-2-en-1-yl, 2,3-dimethylbut-3-en-1-yl, 3,3-dimethyl-but-2-en-1-yl, 1-ethylbut-2-en-1-yl, 1-ethylbut-3-en-1-yl, 2-ethylbut-2-en-1-yl, 2-ethylbut-3-en-1-yl, 1,1,2-trimethyl-prop-2-en-l-yl, 1-ethyl-1-methylprop-2-en-l-yl or 1-ethyl-2-methylprop-2-en-1-yl, in particular prop-2-en-l-yl or n-buten-4-yl;
- C3-C6-haloalkenyl is: C3-C6-alkenyl as mentioned above which is partially or fully substituted by ~luorine, chlorine and/
or bromine, e.g. 2-chloroallyl, 3-chloroallyl, 2,3-dichlo-f_~ roallyl, 3,3-dichloroallyl, 2,3,3-trichloroallyl, 2,3-dichlo-robut-2-enyl, 2-bromoallyl, 3-bl~ ~allyl, 2,3-dibl~ ~allyl, 3,3-dibromoallyl, 2,3,3-tribromoallyl or 2,3-dibromo-but-2-enyl, in particular 2-chloroallyl or 3,3-dichloroallyl;
- cyano-C3-C6-alkenyl is: e.g. 3-cyanoallyl, 4-cyanobut-2-enyl, 4-cyanobut-3-enyl or 5-cyanopent-4-enyl, preferably 3-cya-noallyl or 4-cyanobut-2-enyl, in particular 3-cyanoallyl;
- C3-C4-alkenyloxy-C1-C4-alkyl is: C1-C4-alkyl which is substi-tuted by C3-C4-alkenyloxy, such as prop-2-enyloxy, n-but-2-enyloxy, n-but-3-enyloxy, 1-methylprop-2-enyloxy or 2-methylprop-2-enyloxy, preferably allyloxy, 2-methyl-. 45 prop-2-en-1-yloxy, but-1-en-3-yloxy, but-1-en-4-yloxy or 0050/46586 CA 0224~6~9 l998-08-06 .
but-2-en-1-yloxy, for example allyloxymethyl, 2-allyloxyethyl or but-l-en-4-ylo~y -Lhyl;
- C3-C4-alkenylthio-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by C3-C4-alkenylthio, such as prop-2-enylthio, n-but-2-enylthio, n-but-3-enylthio, 1-methylprop-2-enylthio or 2-methylprop-2-enylthio, preferably allylthio, 2-methyl-prop-2-en-1-ylthio, but-1-en-3-ylthio, but-1-en-4-ylthio or but-2-en-1-ylthio, for example allylthiomethyl, 2-allylthio-ethyl or but-1-en-4-ylthiomethyl;
- C3-C4-alkenylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkenylsulfinyl, such as prop-2-enyl-sulfinyl, n-but-2-enylsulfinyl, n-but-3-enylsulfinyl, l-me-thylprop-2-enylsulfinyl or 2-methylprop-2-enylsulfinyl, pre-ferably allylsulfinyl, 2-methylprop-2-en-1-ylsulfinyl, but-l-en-3-ylsulfinyl, but-1-en-4-ylsulfinyl or but-2-en-1-ylsulfinyl, for example allylsulfinylmethyl, 2-allylsulfinylethyl or but-1-en-4-ylsulfinylmethyl;
- C3-C4-alkenylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkenylsulfonyl, such as prop-2-enylsul-fonyl, n-but-2-enylsulfonyl, n-but-3-enylsulfonyl, 1-methyl-prop-2-enylsulfonyl or 2-methylprop-2-enylsulfonyl, prefera-bly allylsulfonyl, 2-methylprop-2-en-1-ylsulfonyl, but-1-en-3-ylsulfonyl, but-1-en-4-ylsulfonyl or but-2-en-1-ylsulfonyl, for example allylsulfonylmethyl, 2-allylsulfonylethyl or but-1-en-4-ylsulfonylmethyl;
- C3-C6-alkynyl is: e.g. propargyl, n-but-1-yn-3-yl, n-f but-l-yn-4-yl, n-but-2-yn-1-yl, n-pent-1-yn-3-yl, n-pent-l-yn-4-yl, n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl, 3-methylbut-l-yn-3-yl, 3-methylbut-1-yn-4-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5-yl, n-hex-1-yn-6-yl, n-hex-2-yn-l-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2-yn-6-yl, n-hex-3-yn-1-yl, n-hex-3-yn-2-yl, 3-methylpent-1-yn-3-yl, 3-methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl, 4-methyl-pent-2-yn-4-yl or 4-methylpent-2-yn-5-yl, in particular propargyl;
- C3-C6-haloalkynyl is: C3-C6-alkynyl as mentioned above which is partially or fully substituted by fluorine, chlorine and/
or bromine, e.g. 1,1-difluoroprop-2-yn-1-yl, 4-fluoro-but-2-yn-1-yl, 4-chlorobut-2-yn-1-yl, l,l-difluoro-0050~46586 CA 0224~6~9 1998-08-06 .
. .
but-2-yn-1-yl, 5-fluoropent-3-yn-1-yl or 6-fluoro-~ hex-4-yn-1-yl;
- cyano-C3-C6-alkynyl is: e.g. 3-cyanopropargyl;
S
- C3-C4-alkynyloxy-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by C3-C4-alkynyloxy, such as prop-2-ynyloxy, n-but-2-ynyloxy, n-but-3-ynyloxy or 1-methylprop-2-ynyloxy, preferably propargyloxy, but-1-yn-3-yloxy, but-1-yn-4-yloxy or but-2-yn-1-yloxy, for example propargyloxymethyl or 2-propargyloxyethyl;
- C3-C4-alkynylthio-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by C3-C4-alkynylthio, such as prop-2-ynylthio, n-but-2-ynylthio, n-but-3-ynylthio or 1-methylprop-2-ynylthio, preferably propargylthio, but-1-yn-3-ylthio, but-1-yn-4-yl-thio or but-2-yn-1-ylthio, for example propargylth;o~?thyl or 2-propargylthioethyl;
- C3-C4-alkynylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkynylsulfinyl, such as prop-2-ynyl-sulfinyl, n-but-2-ynylsulfinyl, n-but-3-ynylsulfinyl and 1-methylprop-2-ynylsulfinyl, preferably propargylsulfinyl, but-1-yn-3-ylsulfinyl, but-1-yn-4-ylsulfinyl or but-2-yn-1-ylsulfinyl, for example propargylsulfinylmethyl or 2-propargylsulfinylethyl;
- C3-C4-alkynylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkynylsulfonyl, such as prop-2-ynylsul-fonyl, n-but-2-ynylsulfonyl, n-but-3-ynylsulfonyl and 1-me-f. thylprop-2-ynylsulfonyl, preferably propargylsulfonyl, but-1-yn-3-ylsulfonyl, but-1-yn-4-ylsulfonyl or but-2-yn-1-ylsulfonyl, for example propargylsulfonylmethyl or 2-propargylsulfonylethyl;
- C3-C6-cycloalkyl is: cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in particular cyclopentyl or cyclohexyl;
- C3-C8-cycloalkyl is: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, in particular cyclo-pentyl or cyclohexyl;
45 - C3-C8-cycloalkyl-Cl-C4-alkyl is: cyclopropylmethyl, cyclobu-tylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclohep-tylmethyl, cyclooctylmethyl, 1-(cyclopropyl)ethyl, 0050/46586 CA 022456~9 1998-08-06 ~ , .
1-(cyclobutyl)ethyl, 1-(cyclopentyl)ethyl, 1-(cyclohex-yl)ethyl, 1-(cycloheptyl)ethyl, 1-(cyclooctyl)ethyl, 2-(cyclopropyl)ethyl, 2-(cyclobutyl)ethyl~ 2-(cyclopen-tyl)ethyl, 2-(cyclohexyl)ethyl, 2-(cycloheptyl)ethyl, 2-(cyclooctyl)ethyl, 3-(cyclopropyl)propyl, 3-(cyclobu-tyl)propyl, 3-(cyclopentyl)propyl, 3-(cyclohexyl)propyl, 3-(cycloheptyl)propyl, 3-(cyclooctyl)propyl, 4-(cyclopro-pyl)butyl, 4-(cyclobutyl)butyl, 4-(cyclopentyl)butyl, 4-(cyclohexyl)butyl, 4-(cycloheptyl)butyl or 4-(cyclooc-tyl)butyl, in particular cyclopentylmethyl or cyclohexylme_thyl;
- C3-C8-cycloalkoxy-Cl-C4-alkyl is: cyclopropyloxymethyl, cyclobutyloxymethyl, cyclopentyloxymethyl, cyclohexyloxyme-thyl, cycloheptyloxymethyl, cyclooctyloxymethyl, 1-(cyclo-- propyloxy)ethyl, 1-(cyclobutyloxy)ethyl, 1-(cyclopentyl-'~ oxy)ethyl, 1-(cyclohexyloxy)ethyl, 1-(cycloheptyloxy)ethyl, 1-(cyclooctyloxy)ethyl, 2-(cyclopropyloxy)ethyl, 2-(cyclobu-tyloxy)ethyl, 2-(cyclopentyloxy)ethyl, 2-(cyclohexyl-oxy)ethyl, 2-(cycloheptyloxy)ethyl, 2-(cyclooctyloxy)ethyl, 3-(cyclopropyloxy)propyl, 3-(cyclobutyloxy)propyl, 3-(cyclo-pentyloxy)propyl, 3-(cyclohexyloxy)propyl, 3-(cycloheptyl-oxy)propyl, 3-(cyclooctyloxy)propyl, 4-(cyclopropyloxy)butyl, 4-(cyclobutyloxy)butyl, 4-(cyclopentyloxy)butyl, 4-(cyclo-hexyloxy)butyl, 4-(cycloheptyloxy)butyl or 4-(cycloocty-loxy)butyl, in particular cyclopentyloxy-..aLhyl, cyclohexy-loxymethyl or 2-(cyclopentyloxy)ethyl.
30 3- to 7-membered heterocyclyl is to be understood as ~A~;ng not only saturated or partially or fully unsaturated but also aro-matic heterocycles having one to three hetero atoms selected from a group consisting of - one to three nitrogen atoms, 35 - one or two oxygen and - one or two sulfur atoms.
Examples of saturated heterocycles which can contain a carbonyl or thiocarbonyl ring member are:
40 oxiranyl, thiiranyl, aziridin-1-yl, aziridin-2-yl, diaziri-din-l-yl, diaziridin-3-yl, oxetan-2-yl, oxetan-3-yl, thie-tan-2-yl, thietan-3-yl, azetidin-l-yl, azetidin-2-yl, azeti-din-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydro-thiophen-2-yl, tetrahydrothiophen-3-yl, pyrrolidin-l-yl, pyrroli-45 din-2-yl, pyrrolidin-3-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-yl, 1,3-oxathiolan-4-yl, 1,3-oxathiolan-5-yl, 1,3-oxazolidin-2-yl, 1,3-oxazolidin-3-yl, 1,3-oxazolidin-4-yl, ~ OOSO/46586 CA 0224~6~9 l998-08-06 ~ . , .
1,3-oxazolidin-5-yl, 1,2-oxazolidin-2-yl, 1,2-oxazolidin-3-yl, 1,2-oxazolidin-4-yl, 1,2-oxazolidin-5-yl, 1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrroli-din-5-yl, tetrahydropyrazol-l-yl, tetrahydropyrazol-3-yl, te-5 trahydlo~ylazol-4-yl~ tetrahydlo~ylan-2-yl, tetrahydlo~ylan-3 tetrahyd~u~yLan-4-yl~ tetrahydrothiopyran-2-yl, tetrahydloLhi ran-3-yl, tetrahydropyran-4-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1,3-dioxan-2-yl, 1,3-~;ox~n-4-yl, 1,3-dioxan-5-yl, 1,4-~; OxA n-2-yl, 1,3-oxathian-2-yl, 1,3-oxa-lO thian-4-yl, 1,3-oxathian-5-yl, 1,3-oxathian-6-yl, 1,4-oxa-thian-2-yl, 1,4-oxathian-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, hexahyaropyr;~Az;n-l-yl, hexahydropyr;~A~in-3-yl, hexahydropyr; ~A 7; n-4-yl, hexahydlu~yr;~;~in-l-yl~ hexahydropy-rimidin-2-yl, hexahydLo~ ;n-4-yl, hexahydropyrim;~;n-5-yl, 15 piperazin-l-yl, piperazin-2-yl, piperazin-3-yl, hexahy-dro-1,3,5-triazin-1-yl, hexahydro-1,3,5-triazin-2-yl, oxe-. pan-2-yl, oxepan-3-yl, oxepan-4-yl, thiepan-2-yl, thiepan-3-yl, thiepan-4-yl, 1,3-dioxepan-2-yl, 1,3-dioxepan-4-yl, 1,3-dioxe-pan-5-yl, 1,3-dioxepan-6-yl, 1,3-dithiepan-2-yl, 1,3-dithie-20 pan-2-yl, 1,3-dithiepan-2-yl, 1,3-dithiepan-2-yl, 1,4-dioxe-pan-2-yl, 1,4-dioxepan-7-yl, hexahydroazepin-l-yl, hexahydroaze-pin-2-yl, hexahydroazepin-3-yl, hexahydroazepin-4-yl, hexahy-dro-1,3-diazepin-l-yl, hexahydro-1,3-diazepin-2-yl, hexahy-dro-1,3-diazepin-4-yl, hexahydro-1,4-diazepin-l-yl and hexahy-25 dro-1,4-diazepin-2-yl;
Examples of unsaturated heterocycles which can contain a carbonyl or thiocarbonyl ring member are:
dihydrofuran-2-yl, 1,2-oxazolin-3-yl, 1,2-oxazolin-5-yl, 1,3-oxa-30 zolin-2-yl;
Amongst the heteroaromatics, the 5- and 6 :~ cred ones are pre-ferred, e.g. furyl, such as 2-furyl and 3-furyl, thienyl, such as 35 2-thienyl and 3-thienyl, pyrrolyl, such as 2-pyrrolyl and 3-pyr-rolyl, isoxazolyl, such as 3-isoxazolyl, 4-isoxazolyl and 5-iso-xazolyl, isothiazolyl, such as 3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, pyrazolyl, such as 3-pyrazolyl, 4-pyrazolyl and 5-pyrazolyl, oxazolyl, such as.2-oxazolyl, 4-oxazolyl and 5-oxa-40 zolyl, thiazolyl, such as 2-th;A~olyl, 4-thiazolyl and 5-thiazo-lyl, imidazolyl, such as 2-;m;~Azolyl and 4-imidazolyl, OX~;A~O_ lyl, such as OxA~; A ~ol-3-yl~ 1,2,4- OxA~; A ~ol-5-yl and 1,3,4-oxa-diazol-2-yl, thiadiazolyl, such as 1,2,4-th; A~;A701 - 3 - yl, 1,2,4-th; A~; A ~ol-5-yl and 1,3,4-th; A~; A ~ol-2-yl, triazolyl, such 45 as 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl and 1,2,4-triazol-4-yl, - pyridinyl, such as 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, pyridazinyl, such as 3-pyridazinyl and 4-pyridazinyl, pyrimidi-nyl, such as 2-pyrimidinyl, 4-pyr;m;~inyl and 5-pyrimidinyl, fur-~ OOSO/46586 CA 0224~6~9 1998-08-06 , ._-thermore 2-pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl, in particular pyridyl, pyrimidyl, furanyl and thienyl.
All phenyl and heterocyclic rings are preferably unsubstituted or 5 have attached to them a cyano, nitro, halogen, C1-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, (Cl-C4-alkyl)car-bonyl, (C1-C4-alkoxy)carbonyl or (Cl-C4-alkyl)carbonyloxy sub-stituent.
Preferred with a view to the use of the substituted aromatic phosphonic acid derivatives I as herbicides or for the desicca-tion/defoliation of plants are those compounds I where the sub-stituents have the following m~n;ngS~ in each case alone or in 15 combination:
Eth is -CH2-CH(halogen)-, -CH2-CH(CN)-, -CH2-CH(COOCH3)-, -CH=CH-, -CH=C(halogen)-, -CH=C(CN)-, -CH=C(CH3)-, -CH=C(COOCH3)- or -C5C-, in particular -CH2-CH(halogen)- or -CH=C(halogen)-, particularly preferably -CH=C(halogen)-;
yl is oxygen;
y2 is oxygen;
Y3 is oxygen;
R1, R2, R6, R7 independently of one another are hydrogen, C1-C6-alkyl, Cl-C6-haloalkyl, hydroxy-Cl-C4-alkyl, cyano-Cl-C4-alkyl, Cl-C4-alkoxy-Cl-C4-alkyl, di(Cl-C4-alkyl)-amino--Cl--C4--alkyl,Cl--C4--alkylthio-Cl--C4-alkyl, Cl--C4--alkyl--f~ sulfonyl-Cl-C4-alkyl, Cl-C4-haloalkylsulfonyl-Cl-C4-alkyl, ' C3-C6-alkenyl, C3-C6-haloalkenyl, C3-C6-alkynyl, hydroxy-carbonyl--Cl--C4--alkyl,(Cl--C4--alkoxy)carbonyl--Cl--C4-alkyl, aminocarbonyl-Cl-C4-alkyl, (Cl-C4-alkyl)aminocarbonyl-Cl-C4-alkyl, di(Cl-C4-alkyl)aminocarbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-Cl-C4-alkyl, phenyl, phenyl-Cl-Cg-alkyl or 3- to 7-membered heterocyclyl or heterocyclyl-Cl-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or thiocarbonyl ring member, and it being possible for all cycloalkyl, phenyl and heterocyclyl rings to be unsubstituted or to have att~che~
to them one to four substituents, in each case selected from the group consisting of halogen, nitro, amino, hydroxyl, carboxyl, Cl-C4-alkyl, Cl-C4-haloalkyl, 0050/46586 CA 0224~6~9 l998-08-06 . 26 Cl-C4-alkoxy, Cl-C4-alkylsulfonyl, (C1-C4-alkyl)carbonyl, (Cl-C4-alkoxy)carbonyl and di(Cl-C4-alkyl)amino, or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethAne~;yl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four Cl-C4-alkyl and/or one or two (C1-C4-alkoxy)carbonyl groups, R1, R2, R6, R7 are, in particular, in each case hydrogen, Cl-C6-alkyl, Cl-C6-haloalkyl, C3-C6-alkenyl, C3-C6-haloalkenyl, C3-C6-alkynyl, (C3-C4-alkoxy)carbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-Cg-cycloalkyl-C1-Cq-alkyl, ~ phenyl, phenyl-C1-C4-alkyl or 3- to 7-membered heterocyclyl ' or heterocyclyl-C1-C4-alkyl or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethanediyl or 1,3-propylene chain;
R1, R2, R6, R7 is particularly preferably in each case hydrogen, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, phenyl or phenyl-Cl-C4-alkyl, or R1 and R2 together form a 1,3-propylene chain;
R3 is cyano, halogen or C1-C4-haloalkyl, in particular halogen, particularly preferably chlorine;
R4 is h.ydrogen, fluorine or chlorine, in particular fluorine or chlorine, particularly preferably fluorine;
R5 is one of the following heterocycles ~1 to ~5, ~7, ~20, ~21 . and ~22:
. 45 ~ 0050/46586 CA 02245659 l998-08-06 .
R9 N ~ 0 ~ N~ Rl ~ N' ~ ~3 ~ _ y4 R 6 Rl7 ,r Rl9 R18 R23 R~ N
N k ' Rs3 Rs2 ,~ Rsl \
S ~ N - ~50 ~20 ! ~ S
~ R54 N~
I S ~22 Rs6~ ~ N
where R8 is methyl;
R9 is Cl-C4-haloalkyl, in particular trifluoromethyl;
45 Rlo is Cl-C4-alkyl, in particular methyl;
0050/46586 CA 0224~6~9 1998-08-06 Rll is Cl-C4-haloalkyl, in particular trifluoromethyl, or Cl-C4-halo~lko~y, in particular difluoromethoxy;
Rl2 is halogen, in particular chlorine, or Cl-C4-haloalkyl, in particular trifluoromethyl;
Y4 is oxygen;
lO Rl3 and Rl4independently of one another are Cl-C4-alkyl, in particular methyl, or Rl3 and Rl4together with the ring atoms l;nk;ng them are a 6: '~red carbocyclic ring;
Rl5 and Rl6together with the ring atoms linking them are a 6 . --h~red carbocyclic ring;
20 Rl7 is halogen, in particular chlorine;
Rl8 is chlorine or bromine, in particular chlorine;
25 Rl9 is halomethyl, in particular difluoromethyl;
R20 is Cl-C4-alkyl, in particular methyl;
R23 and R24together with the ring atoms linking them are a 6-mem-bered ring;
~_. Y7 is oxygen;
35 R50 is Cl-C4-alkyl, in particular methyl;
Rsl is Cl-C4-haloalkyl, in particular trifluoromethyl;
Rs2 is hydrogen;
R53 and R54 together with the ring atoms l;nk;ng them are a 6-mem-bered ring;
45 Z3, z4 independently of one another are nitrogen;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
R55 and R56 together with the ring atoms linking them are a 5- or 6 7 cred ring which, if desired, can additionally have attached to it one or two Cl-C4-alkyl substituents;
5 R5 is especially preferably 1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyri m; ~; ne~;on-3-yl, 4-chloro-5-difluoro-methoxy-1-methyl-lH-pyrazol-3-yl, 4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl, 1-methyl-4,5-di(trifluoromethyl)-lH-pyrazol-3-yl, 1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl, 10 3,4-dimethyl-lH-pyrrol-2,5-dion-1-yl, 3-chloro-4,5,6,7-tetra-hydro-2H-indazol-2-yl, 5-chloro-1-difluoromethyl-2-methyl-lH-~ ol-4-yl, 5,6,7,8-tetrahydro-1,2,4-triazolot4,3-a]pyridin-3(2H)-on-2-yl, (3-methyl-4-trifluoromethyl-2(3H)-thiazolyli-dene)amino, (tetrahydro-3-oxo-lH,3H-[1,3,4]th;~ zolo-15 [3,4-a]pyridazin-1-yl;~e)amino or (6,7-dihydro-6,6-dimethyl-r 3H, 5H ~yLLolo [ 2 ~ l--c ] t l, 2, 4 ] th; ~ ol--3--ylidene ) amino .
~.
Very especially preferred are the compounds IAa listed in Table 1 below (~ I where R3 = chlorine; Eth 5 -CH2-CH2-; R5 = heterocycle ~1 where R3 = CH3 and R9 = CF3):
~.
.
, 0050/46586 CA 02245659 l998-os-06 ~ . .
Table 1 ~ N
~ ~=O
~ N ~,1 IAa 10 R4 ~ CH2 CH~--' y Cl y3R2 15 No. R4 -P(=Yl)(y2Rl)(y3R2) LAa.l H -P(=O)(OH)2 IAa.2 H -p(=o)(ocH3)2 LAa.3 H -P(=O)(OC2Hs)2 IA~.4 H -p(=o)[o-(n-c3H7)]2 LAa.S H -P(=O)tOCH(CH3)2]2 LAa.6 H -P(=O)[O-(n-CiHs)]2 LAa.7 H -p(=o)[ocH2-cH(cH3)2]2 IAa.8 H -P(=O)[OCH(CH3)-C2H5]2 25 IA~.9 H -P(=0)(0CH2-CF3)2 IA~.10 H -P(=O)(OCH2-CH2-OH)2 IAa.ll H -p(=o)(ocH2-cH2-cN~2 L~a.12 H -p(=o)(ocH2-cH2-ocH3)2 30 IAa.13 H -p(=o)(ocH2-cH2-oc2H5)2 IAa.14 H -p(=o)(ocH2-cH2-ocF3)2 ,~ IAa.15 H -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 IAa.16 H -P(=O)(OCH2-CH2-OCH2-C----CH)2 35 IAa.17 H -P(=O)(OCH2-CH2-0-cyclopentyl~2 IAa.18 H -p(=o)(ocH2-cH2-NH2)2 IAa.l9 H -p(=o)(ocH2-cH2-NH-cH3)2 IAa.20 H -p(=o)[ocH2-cH2-N(cH3)2]2 LAa.21 H -P(=O)(OCH2-CH2-SCH3)2 40 L~a.22 H -P(=O)(OCH2-CH2-SC2H5)2 IAa.23 H -p(=o)(ocH2-cH2-scF3)2 IAa.24 H -P(=O)(OCH2-CH2-SCH2-CH=CH2)2 IAa.25 H -P(=O)(OCH2-CH2-SCH2-C----CH)2 45 IAa.26 H -P(=O)(OCH2-CH2-SO-CH3)2 IAa.27 H -p(=o)(ocH2-cH2-so-c2H5)2 IAa.28 H -p(=o)(ocH2-so2-cH3)2 0050/46586 CA 022456s9 1998-08-06 No. R4 _p(=yl)(Y2R1)(Y3R2) IAa.29 H -p(=o)(ocH2-so2-c2Hs)z IAa.30 H -p(=o)(ocH2-cH2-so2-cH3)2 IAa.31 H -p(=o)(ocH2-cH2-so2-c2Hs)2 IAa.32 H -p(=o)(ocH2-cH=cH2)2 IAa.33 H -P(=O)(OCH2-CH=CH-C~3)2 IAa.34 H -p(=o)(ocH2-cH2-cH=cH2)2 IAa.35 H -P(=O)(OCH2-CH=CH-Cl~Q
IAa.36 H -P(=O)(OCH2-C----CH)2 IAa.37 H -P(=O)[OCH~CH3)-C--CH]2 IAa.38 H -p(=o)(ocH2-co-ocH3)2 IAa.39 H -p(=O)(OCH2-CO-OC2Hs)2 IAa.40 H -P(=O)[OCH(CH3)-CO-OCH3]2 - IAa.41 H -P(=O)[OCH(CH3)-CO-OC2Hs]2 IAa.42 H -p(=o)(ocH2-co-N~2)2 IAa.43 H -p(=o)(ocH2-co-NH-c~3)2 IAa.44 H -p(=o)[ocH2-co-N(cH3)2]2 IAa.45 H -P(=O) OCH(CH3)-CO-N~2]2 IAa.46 H -P(=O) OCH(CH3)-CO-NH-C~]2 IAa.47 H -P(=O) OCH(CH3)-CO-N(CH3)2]2 2S IAa.48 H -P(=O)(O-cyclopropyl~Q
IAa.49 H -P(=O)(O-cyclobutyl~2 IAa.50 H -P(=O)(O-cyclopentyl~z IAa.51 H --P(=O)(O-cyclohexYl~2 IAa.52 H -P(=O)(OCH2-cyclopropyl~2 LAa.53 H -p(~o)(ocH2-cyclobutyl~2 ~IAa.54 H -p(=o)(ocH2-cyclopentyl~2 '~-IAa.55 H -p(=o)(ocH2-cyclohexyl~2 IAa.56 H -p(=o)(o-phenyl~2 3 5 L~a.57 H -p(=o)(ocH2-phenyl~2 IAa.58 H -P(=O)(O-oxetan-3-yl~
IAa.59 H --P(=O)(O-tetraLyd.ùru~ -2-yl~
IAa.60 H -P(=O)(O-tetrahy~l.ofu,dll-3-yl~
~,o IAa.61 H -P(=O)(O-tetrahyd.o~,y.~n-2-yl~
IAa.62 H -P(=O)(O-tetrahydlo~y.~n-3--yl~
IAa.63 H -P(=O)(O-tetraLyd.u~.y.~n-4-yl~
IAa.64 H -P(=O)(OCH2-o~iran-2-yl~
IAa.65 H -P(=O)(OCH2-oxetan--3-yl}~
IAa.66 H -P(=O)(OCH2-tetrahydrofuran-2-yl~
IAa.67 H -P(=O)(OCH2-tetrahydrofuran-3-yl~
0050/46586 CA 0224s6ss l998-08-06 No. R4 _p(=yl)cy2Rl)(y3R2) IAa.68 H --P(=O)(OCH2-pyrrolidin-l-ylk IAa.69 H -P(=O)[OCH2-(2-pyrrolidon-l-yl)~
5 IAa.70 H --P(=O)(OCH2-tetrahy~l~o~y~an-2-yl~
IAa.71 H -P(=O)(OCH2-tetral ylLo~y~an-3-yl~
IAa.72 H --P(=O)(OCH2-tetrally~1lo~-4-yl~2 IAa.73 H --P(=O)(OCH2-piperidin-l-yl~
IAa.74 H --P(=O)(OCH2--morpholin.-4-yl~
IAa.75 H -P(=O)(OH)(OCH3) IAa.76 H -P(=O)(OH)(OC2Hs) IAa.77 H --P(=O)(OH)[O-[n-C3H7)]
IAa.78 H -P(=O)(OH)[OCH(CH3)2]
15 IAa.79 H -P(=O)(OH)[O-(n-CiHg)]
~~IAa.80 H --P(=O)(OH)[OCH2-CH(CH3)2]
IAa.81 H -P(=O)(OH)[OCH(CH3)-c2Hs]
IAa.82 H -P(=O)(OH)(OCH2-CF3) 20 IAa.83 H -P(=O)(OH)(OCH2-CH2-OH) IAa.84 H -P(=O)(OH)(OCH2-CH2-CN) IAa.85 H -P(=O)(OH)(OCH2-CH2-OCH3) IAa.86 H -P(=O)(OH)(OCH2-CH2-OC2Hs) 25 IAa.87 H -P(=O)(OH)(OCH2-CH2-OCF3) IAa.88 H -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) LAa89 H -P(=O)(OH)(OCH2-CH2-OCH2-C-- CH~
LAa.90 H -P(=O)(OH)(OCH2-CH2-O-cyclopentyl) L~a.91 H -P(=O)(OH~(OCH2-CH2-NH2) IAa.92 H -P(=O)(OH)(OCH2-CH2-NH-CH3) IAa.93 H -P(=O)(OH)[OCH2-CH2-N(cH3)2]
IAa.94 H -P(=O)(OH)(OCH2-CH2-SCH3) IAa.95 H -P(=O)(OH9(0CH2-CH2-SC2Hs) 35 IAa.96 H -P(=O)(OH)(OCH2-CH2-SCF3) IAa.97 H -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.98 H -P(=O)(OH)(OCH2-CH2-SCH2-C_ CH) IAa.99 H -P(=O)(OH)(OCH2-CH2-SO-CH3) 40 IAa.100 H -P(=O)(OH)(OCH2-CH2-SO-C2Hs) IAa.101 H -P(=O)(OH)(OCH2-SO2-CH3) LAa.102 H -P(=O)(OH)(OCH2-SO2-C2Hs) IAa.103 H -P(=O)(OH)(OCH2-CH2-SO2-CH3) IAa.104 H -P(=O)(OH)(OCH2-CH2-SO2-C2Hs) IAa.105 H -P(=O)(OH9(0CH2-CH=CH2) IAa.106 H -P(=O)(OH)(OCH2-CH=CH-CH3) 0050/46586 CA 0224~6~9 l998-08-06 No. R4 -P(=yl)(y2Rl)(y3R2) L~a.107 H -P(=O)(OH)(OCH2-CH2-CH=CH2) L~a.108 H -P(=O)(OH)(OCH2-CH=CH-Cl) IAa.109 H -P(=O)(OH)(OCH2-C= CH) IAa.110 H -P(=O)(OH)[OCH(CH3)-C--CH]
LAa.111 H -P(=O)(OH)(OCH2-CO-OCH3) IAa.112 H -P(=O)(OH)(OCH2-CO-OC2Hs) L~a.113 H -P(=O)(OH)[OCH(CH3)-CO-OCH3]
IAa114 H ~p(=o)(oH)[ocH(cH3)-co-oc2Hs]
IAa.115 H -p(=o)(oH)(ocH2-co-NEI2) IAa.116 H -P(=O)(OH)(OCH2-CO-NH-CEO
IAa.117 H _p(=o)(oH)[ocH2-co-N(cH3)2]
IAa.118 H -P(=O)(OH)[OCH(CH3)-CO-NH2]
IAa.119 H -P(=O)(OH)[OCH(CH3)-CO-NH-C~]
IAa.120 H -P(=O)(OH)[OCH(CH3)-CO-N(CH3)2]
L~a.121 H -P(=O)(OH)(O-cyclopropyl) IAa.122 H -P(=O)(OH)(O-cyclobutyl) IAa.123 H -P(=O)(OH)(O-cyclopentyl) IAa.124 H -P(=O)(OH)(O-cyclohexyl) IAa.125 H -P(=O)(OH)(OCH2-cyclop}opyl) IAa.126 H -P(=O)(OH)(OCH2-cyclobutyl) IAa.127 H -P(=O)(OH)(OCH2-cyclopentyl) IAa.128 H -P(=O)(OH)(OCH2-cyclohe~cyl) IAa.129 H -P(=O)(OH)(O-phenyl) IAa.130 H -P(=O)(OH)(OCH2-phenyl) IAa.131 H -P(=O)(OH)(O-oxetan-3-yl) IAa.132 H -P(=O)(O~(O-tetrahyd.uru.dn-2-yl) IAa.133 H -P(=O)(OH)(O-tetrahylLoru~ -3-yl) IAa.134 H -P(=O)(OH)(O-tetral yd.u~gldn-2-yl) IAa.135 H -P(=O)(OH)(O-tetrahg~Lo~.an-3-yl) IAa.136 H -P(=O)(OH)(O-tetraLg~o~,g.dll-4-yl) IAa.137 H -P(=O)(OH)(OCH2-oxiran-2-yl) IAa.138 H -P(=O)(OH)(OCH2-o~etan--3--yl) IAa.139 H -P(=O)(OH)(OCH2-tetrahydrofuran-2-yl) IAa.140 H -P(=O)(OH)(OCH2-tetrahydrofuran-3-yl) IAa.141 H -P(=O)(OH)(OCH2-pyrrolidin-1-yl) IAa.142 H -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
IAa.143 H -P(=O)(OH)(OCH2-tetrahydropyran-2-yl) IAa.144 H -P(=O)(OH)(OCH2-tetrahyd.u~g.an-3-yl) IAa.145 H -P(=O)(OH)(OCH2-tetrahyd.o~y.dn-4-yl) 0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=yl)cy2Rl)~y3R2) IAa.146 H -P(=O)(OH)(OCH2-piperidin-l-yl) IAa.147 H -P(=O)(OH)(OCH2-morpholin-4-yl) IAa.148 H -p(=o)(ocH3)(oc2Hs) IAa.149 H -p(=o)(ocH3)[o-(n-c3H7)]
IAa.150 H -P(=Q)(0CH3)[0CH(CH3)2]
IAa.151 H -P(=O)(OCH3)[0-(n--C J,Hg)]
IAa.152 H -P(=0)(0CH3)[0CH2-CH(CH3)2]
IAa.153 H -P(=0)(0CH3)[0CH(CH3)-C2H5]
L~a.154 H -P(=O)(OCH3)(0CH2-CF3) IAa.155 H -P(=O)(OCH3)(0CH2-CH2-OH) L~a.156 H -P(=O)(OCH3)(0CH2-CH2-CN) 15 IAa.157 H -P(=O)(OCH3)(0CH2-CH2-OCH3) ~- IAa.158 H -P(=O)(OCH3)(0CH2-CH2-0C2Hs) IAa.159 H -P(=O)(OCH3)(0CH2-CH2-OCF3) L~a.160 H -P(=O)(OCH3)(0CH2-CH2-0CH2-cH=cH2) 20 IAa.161 H -P(=0)(0CH3)(0CH2-CH2-OCH2-C5 CH) IAa.162 H -P(=O)(OCH3)(0CH2-CH2-0-cyclopentyl) IAa.163 H -P(=0)(0CH3)(0CH2-CH2-NH2) IAa.164 H -P(=O)(OCH3)(0CH2-CH2-NH-CE0 25 IAa.165 H -P(=0)(0CH3)[0CH2-CH2-N(CH3)2]
IAa.166 H -P(=O)(OCH3)(0CH2-CH2-SCH3) IAa.167 H -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.168 H -P(=O)(OCH3)(0CH2-CH2-SCF3) IAa.169 H -p(=o)(ocH3)(ocH2-cH2-scH2-cH=cH2) IAa.170 H -P(=O)(OCH3)(0CH2-CH2-SCH2-C5 CH) f~ L~a.171 H -P(=O)(OCH3)(0CH2-CH2-SO-CH3) ~-; IAa.172 H -P(=0)(0CH3)(0CH2-CH2-S0-C2H5) IAa.173 H -P(=O)(OCH3)(OCH2-SO2-CH3) 35 IAa.174 H -P(=0)(0CH3)(0CH2-S02-C2Hs) IAa.175 H -P(=O)(OCH3)(0CH2-CH2-S02-CH3) IAa.176 H -P(=0)(0CH3)(0CH2-CH2-S02-C2H5) IAa.177 H -P(=O)(OCH3)(OCH2-CH=CH2) 40 IAa.l78 H -P(=O)(OCH3)(0CH2-CH=CH-CH3) IAa.179 H -P(=0)(0CH3)(0CH2-CH2-CH=CH2) IAa.180 H -P(=O)(OCH3)(OCH2-CH=CH-Cl) IAa.181 H -P(=O)(OCH3)(0CH2-C5 CH) IAa.182 H -p(=o)(ocH3)[ocH(cH3)-ce CH]
IAa.183 H -P(=O)(OCH3)(0CH2-C0-OCH3) IAa.184 H -P(=O)(OCH3)(OCH2-CO-OC2Hs) 0050~46586 CA 0224~6~9 l998-08-06 ~ . .
No. R4 -p(=yl)cy2Rl)cy3R2) IAa.185 H -P(=O)(OCH3) OCH(CH3)-CO-OCH3]
IAa.186 H -P(=O)(OCH3) OCH(CH3)-CO-OC2Hs]
IAa.187 H -P(=O)(OCH3)(0CH2-CO-NH2) IAa.188 H -P(=O)(OCH3)(0CH2-CO-NH-CH~) IAa.189 H -p(=o)(ocH3)[ocH2-co-N(c~l3)2]
IAa.l90 H -p(=o)(ocH3)tocH(cH3)-co-N~2]
IAa.l91 H -P(=O)(OCH3)[0CH(CH3)--CO-NH-C~]
IAa.192 H -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.193 H --P(=O)(OCH3)(0-cyclopropyl) IAa.194 H -P(=O)(OCH3)(0-cydobutyl) IAa.l95 H -P(=O)(OCH3)(0-cyclopentyl) IAa.196 H -P(=O)(OCH3)(0-cyclohe~yl) ~ IAa.197 H -P(=O)(OCH3)(0CH2-cyclopropyl) IAa.198 H -P(=O)(OCH3)(0CH2-cyclobutyl) IAa.l99 H -P(=O)(OCH3)~0CH2-cyclopentyl) IAa.200 H -P(=O)(OCH3)(0CH2-cydohe~yl) IAa.201 H -P(=O)(OCH3)(0-phenyl) IAa.202 H -P(=O)(OCH3)(0CH2-phenyl) IAa.203 H -P(=O)(OCH3)(0-oxetan-3-yl) IAa.204 H -P(=O)(OCH3)(0-tetral y.lloru.all-2-yl) IAa.205 H -P(=O)(OCH3)(0-tetraLy-i.orulan-3-yl) IAa.206 H -P(=O)(OCH3)(0-tetrahyd o~y.an-2-yl) IAa.207 H -P(=O)(OCH3)(0-tetrahyd~opy~àn-3-yl) IAa.208 H -P(=O)(OCH3)(0-tetraLyd.o~ylan-4--yl) IAa.209 H -P(=O)(OCH3)(0CH2-o~ciran-2-yl) ,~ IAa.210 H -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.211 H -P(=O)(OCH3)(0CH2-tetrahyd.vru.all-2-yl) IAa.212 H --P(=O)(OCH3)(0CH2--tetrahyd.vru.an-3-yl) IAa.213 H -P(=O)(OCH3)(0CH2-pyrrolidin-1-yl) IAa.214 H -P(=O)(OCH3)[0CH2-(2--pyrrolidon-l-yl)]
IAa.215 H -P(=O)(OCH3)(0CH2-tetrahy~vl,y.an-2-yl) IAa.216 H -P(=O)(OCH3)(0CH2-tetrahydlopylan-3-yl) IAa.217 H -P(=O)(OCH3)(0CH2-tetrahydlv~ylan~-yl) IAa.218 H -P(=O)(OCH3)(0CH2-piperidin-1-yl) IAa.219 H -P(=O)(OCH3)(0CH2-morpholin-4-yl) IAa.220 H -P(=o)(oc2Hs) O-(n-C3H7)]
IAa.221 H --P(=O)(OC2Hs) OCH(CH3)2]
IAa.222 H -P(=O)(OC2Hs) O-(n-(~Hs)]
IAa.223 H -P(=O)(OC2Hs) 0CH2-CH(CH3)2]
0050~46586 CA 0224~6~9 l998-08-06 No. R4 P(=Yl)CY2Rl)(y3Rz) LA~.224 H -p(=o)(oc2Hs)locH(cH3)-c2Hs]
LAa.225 H -P(=O)(OC2Hs)(OCH2-CF3) LA a.226 H -P(=O)(OC2H5)(0CH2-CH2-OH) LAa.227 H -P(=O)(OC2Hs)(OCH2-CH2-C~
LA~.228 H -P(=O)(OC2H5)(0CH2-CH2-OCH3) LAa.229 H -P(=O)(OC2Hs)(OCH2-CH2-OC2H5) LAa.230 H -P(=O)(OC2H5)(0CH2-CH2-OCF3) LAa.231 H -p(=o)(oc2H5)(ocH2-cH2-ocH2-cH=cH2) I~.232 H -P(=O)(OC2H5)(OCH2-CH2-OCH2-Ca CH) LAa.233 H -P(=O)(OC2H5)(0CH2-CH2-O-cyclopen~l) I~a.234 H -P(=O)(OC2H5)(0CH2-CH2-NH2) L9a.235 H -P(=O)(OC2H5)(0CH2-CH2--NH-CH3) LAa.236 H -P(=O)(OC2H5)[ocH2-cH2-N(cH3)2]
LAa.237 H -P(=O)(OC2H5)(0CH2-CH2-SCH3) LA~.238 H -P(=O)(OC2H5)(0CH2-CH2--SC2H5) I~.239 H -P(=O)(OC2H5)(OCH2-CH2-SCF3) LAa.240 H -P(=O)(OC2H5)(0CH2-CH2-SCH2-CH=CH2) LAa.241 H --P(=O)(OC2Hs)(OCH2--CH2--SCH2-Ca CH) LAa.242 H -P(=O)(OC2Hs)(OCH2-CH2--SO-CH3) I~.243 H -P(=O)(OC2H5)(OCHz-CH2 - SO-C2H5) LAa.244 H -P(=o)(oc2H5)(ocHz-so2-cH3) LAa.245 H -P(=O)(OC2H5)(0CH2-SOz-C2Hs) LAa.246 H -P(=O)(OC2H5)(0CH2--CH2-SO2-CH3) LAa.247 H -P(=O)(OC2H5)(ocH2-cH2 - SO2-C2H5) I~a.248 H -P(=O)(OC2Hs)(OCH2-CH=CHz) LAa.249 H -P(=O)(OC2Hs)(OCH2-CH=CH-CH3) ~_ LAa.250 H -p(=o)(oc2Hs)(ocH2-cH2-cH=cH2) I~a.251 H -P(=O)(OC2Hs)(OCH2-CH=CH-CI) LAa.252 H -P(=O)(OC2Hs)(OCH2-C - CH) I~a.253 H -P(=O)(OC2Hs)[oCH(CH3) - Ca CH]
I~.254 H -P(=O)(OC2H5)(OCH2-CO-OC~O
LAa.255 H -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~a.256 H -P(=O)(OC2H5)[0CH(CH3)-CO-OCH3]
I~.257 H -P(=O)(OC2H5)[OCH(CH3)-CO-OC2H5]
IAa.258 H -P(=O)(OC2H5)(0CH2-CO-NH2) LAa.259 H -P(=O)(OC2H5)(OCH2-CO-NH-CHO
LAa.260 H -p(=o)(oc2H5)[ocH2-co-N(c~3)2]
- IAa.261 H -P(=O)(OC2H5) OCH(CH3)-CO-NH2]
I~a.262 H -P(-O)(OC2H5) OCH(CH3)-CO-NH-CH3]
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)(y2R1)~3R2) IAa.263 H -p(=o)(oc2Hs)[ocH(cH3)-co-N(cH3)2]
IAa.264 H -P(=O)(OC2Hs)(O-cyclopropyl) 5 IAa.265 H -P(=O)(OC2Hs)(O-cyclobutyl) IAa.266 H -P(=O)(OC2Hs)(O-cyclopentyl) IAa.267 H ~P(=o)(oc2Hs)(o-cyclohexyl) IAa.268 H --P(=O)(OC2Hs)(OCH2-cyclop.. ,l,yl) IAa.269 H -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.270 H -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa271 H ~P(=o)(oc2Hs)(ocH2-cyclohe~yl) IAa.272 H -P(=O)(OC2Hs)(O-phenyl) IAa.273 H ~P(=o)(oc2Hs)(ocH2-phenyl) IAa.274 H --P(=O)(OC2Hs)(O-oxetan-3-yl) ,~ IAa.275 H --P(=O)(OC2Hs)(O-tetrahydloru.dn-2--yl) IAa.276 H -p(=o)(oc2Hs)(o-tetraLy~Loruldn-3-yl) IAa.277 H -P(=O)(OC2Hs)(O-tetrahy ~ o~y. an-2-yl) IAa.278 H -P(=O)(OC2Hs)(O--tetra~ydl~yldn--3-yl) IAa.279 H -P(=O)(OC2Hs)(O-tetrahyd.o~y.d.l-4-yl) IAa.280 H -P(=O)(OC2Hs)(OCH2-oxiran-2-yl) IAa.281 H ~P(=O)(oc2Hs)(ocH2-oxetan-3-yl) 2 5 IAa.282 H -P(=O)(OC2Hs)(OCH2-tetrahydrofuran--2-yl) IAa.283 H -P(=O)(OC2Hs)(OCH2-tetrahyd.c,ru~dn-3--yl) IAa.284 H ~P(=o)(oc2Hs)(ocHz-pyrrolidin-l--yl) IAa.285 H --P(=O)(OC2Hs)tOCH2-(2-pyrrolidon--1-yl)]
IAa.286 H -P(=O)(OC2Hs)(OCH2-tetrahyLo~,y.all-2-yl) IAa.287 H -P(=O)(OC2Hs)(OCH2-tetrahy&o~y.an-3-yl) IAa.288 H -P(=O)(OC2Hs)(OCH2-tetrahy~.opy.dn-4-yl) IAa.289 H --P(=O)(OC2Hs)(OCH2--pir~ri~lin--1--yl) IAa.290 H --P(=O)(OC2Hs)(OCH2-morpholin-4--yl) IAa.291 H -P(=0)(1,2-phenylenedio~y) IAa.292 H -P(=O)(O-CH2-CH2-O) IAa.293 H --P(=O) O--CH(CH3)--CH2-o]
IAa.294 H -P(=O) O-CH(CE~3)-CH(CH3)-O]
IAa.295 H -P(=O) O-CH(COOCH3)-CH(COOCH3)-O]
IAa.296 H -P(=O)~ O-C~2-CH2-CH2-O) IAa.297 H --P(=O)[O-CH-C(CH3)2-CH2--O]
IAa.298 H -P(=O)(O-C~2-CH2-CH2-CH2-O) 45 IAa.299 H -P(-S)(OH)2 IAa.300 H -P(=S)(OCH3)2 IAa.301 H --P(=S)(OC2Hs)2 -~ 38 -No. R4 -P(=yl)(y2Rl)(y3R2) IAa.302 H -P(=S)~O-(n-C3H7)]2 IAa.303 H -p(=s)[o-(n-~,H9)]2 S LAa.304 H -P(=s)(o-c~2-cH2-cH2-o) IAa.305 H -p(=o)(NH2)2 IAa.306 H -P(=O)(NH-CH3)2 IAa.307 H -p(=o)~N(cH3)2]2 L9a.308 H -p(=o)(NH-c2Hs)2 IAa.309 H -p(=o)[N(c2Hs)2]2 IAa.310 H -P(=O)(NH-CH2-CH=CH2)2 IAa.311 H -P(=O)(NH-CH2-C--CH)2 IAa.312 H -P(=O)(NH-cyclopropyl)2 IAa.313 H -p(=o)(NH-cE~2-cyclopentyl)2 C IAa.314 H --P(=O)(NH-phenylk IAa.315 H -p(=o)(NH-cH2-phenyl~2 IAa.316 H --P(=O)(pyrrolidin-1--yl~
IAa.317 H -P(=0)(2-meth~y~l,ol.ylyy.. olidin-1-yl~
IAa.318 H -P(=O)(NH-CH2-CO-OC~3)2 IAa.319 H --P(=O)[N(CH3)-CH2-CO-OCH3]2 IAa.320 H -p(=o)(NH-cK2-co-oc2Hs)2 2 5 IAa.321 H --P(=O)[N(CH3)-CH2-CO-Oc2Hs]2 IAa.322 H -P(=O)~NH-CH(CH33-CO-OCH3]2 IAa.323 H -P(=O)(OH)(NH2) IAa.324 H -P(=O)(OH)(NH-CH3) IAa.325 H -P(=O)(OH)rN(CH3)2]
IAa.326 H -P(=O)(OH)(NH-C2Hs) C IAa.327 H -P(=O)(OH)[N(C2Hs)2]
IAa.328 H -P(=O)(OH)(NH-CH2-CH=CH2) IAa.329 H -P(=O)(OH)(NH-CH2-C_ CH) 3 5 IAa.330 H -P(=O)(OH)(NH-cyclopropyl) L~a.331 H -P(=O)(OH)(NH-CH2-cyclopentyl) IAa.332 H -P(=O)(OH)(NH-phenyl) IAa.333 H -p(=o)(oH)(NH-cH2-phenyl) 40 IAa.334 H -P(=O)(OH)(pyrrolidin-1-yl) IAa.335 H -P(=O)(OH)(2-methoxyca-l,o~yl~,.olidin-1-yl) IAa.336 H -P(=O)(OH)(NH-CH2-CO-OCH3) IAa.337 H -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
45 IAa.338 H -P(=O)(OH)(NH-CE~z-CO-OC2Hs) IAa.339 H -P(=O)(OH) N(CH3)-CH2-CO-OC2Hs]
L~a.340 H -P(=O)(OH)-NH-CH(C~3)-CO-OC~3]
0050/46586CA 0224~6~9 l998-08-06 39 _ No.R4 _p(=yl)~Y2Rl)(Y3R2) IAa.341 H -P(=O)(OCH3)(NH2) IAa.342 H -P(=O)(OCH3)(NH-CH3) 5 IAa.343 H -P(=O)(OCH3)[N(CH3)2]
IAa.344 H -P(-O)(OCH3)(NH-C2Hs) IAa.345 H -P(=O)(OCH3)[N(C2Hs)2]
IAa.346 H -P(=O)(OCH3)~NH-CH2-CH=CH2) IAa.347 H -P(=O)(OCH3)~NH-CH2-CeCH) IAa.348 H -P(=O)(OCH3)~H-cyclopropyl) IAa.349 H -P(=O)(OCH3)~NH-CH2-cyclopentyl) IAa.350 H --P(=O)(OCH3)(NH-phenyl) IAa.351 H -P(=O)(OCH3)~NH-CH2-phenyl) 15 IAa.352 H -P(=O)(OCH3)(pyrrolidin-l-yl) f;IAa.353 H -P(=O)(OCH3)(2-metho~yc~l,ollyl~ olidirl-l-yl) IAa.354 H -P(=O)(OCH3)~#H-CH2-CO-OCH3) IAa.355 H -P(=O)(OCH3)~N(CH3)-CH2-CO-OCH3]
20 IAa.356 H -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.357 H -p(=o)(ocH3)[N(cH3)-cH2-co-oc2Hs]
IAa.358 H -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
IAa.359 H -p(=o)(oc2Hs)~NH2) 25 IAa.360 H -P(=O)(OC2Hs)(NH-CH3) IAa.361 H -p(=o)(oc2Hs)[N(cH3)2]
IAa.362 H -P(=O)(OC2Hs)(NH-C2Hs) IAa.363 H -p(=o)(oc2Hs)[N(c2Hs)2]
IAa.364 H -P(=O)(OC2Hs)(NH-CH2-CH=CH2) IAa.365 H -P(=O)(OC2Hs)(NH-CH2-C--CH~
IAa.366 H -P(=O)(OC2Hs)(NH-cyclopropyl) CIAa.367 H -P(=O)(OC2Hs)~NH-CH2-cyclopentyl) IAa.368 H ~P(=o)(oc2Hs)(NH-phenyl) 35 IAa.369 H -P(=O)(OC2Hs)(NH-CH2-phenyl) L~a.370 H -P(=O)(OC2Hs)(pyrrolidin-l-yl) IAa.371 H -P(=O)(OC2Hs)(2-metho~.l)ollyl~Jyl.olidin-l-yl) IAa.372 H -P(=O)(OC2Hs)(NH-CH2-CO-OC~3) 40 IAa.373 H -P(=O)(OC2Hs)[N(CH3)-CH2-CO-OCH3]
IAa.374 H -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.375 H -P(=O)(OC2Hs) N(CH3)-CH2-CO-OC2Hs]
IAa.376 H -P(=O)(OC2Hs) NH-CH(CH3)-CO-OCH3]
45 IAa.377 H - P(=O) N(CH3)2](0cH3) IAa.378 H -P(=O) N(CH3)2](0C2Hs) IAa.379 H --P(=O) N(CH3)2][0-(n-C3H?)]
0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=yl)(y2Rl)~y3R2) IAa.380 H --P(=O)[N(CH3)2][0CH(CH3)2]
IAa.381 H -P(=o)[N(cH3)2][o-(n-ciHs)]
IAa.382 H -P(=O)[N(CH3)2](0CH2-CH=CH2) IAa.383 H --P(=O)[N(CH3)2 (OCH2-Ca CH) IAa.384 H -P(=O)[N(CH3)2 (O-cyclohe~yl) IAa.385 H -P(=O)[N(CH3)2 (OCH2-cyclohe~yl) IAa.386 H -P(=O)[N(CH3)2 (O-phenyl) IAa.387 H -P(=O)[N(CH3)2 (OCH2-phenyl) IAa.388 H -P(=O)[N(CH3)2 (O-tetrahy~L. ruldn-2-yl) IAa.389 H ~p(=o)[N(cH3)2](ocH2-o~e IAa.390 H -P(=O)[N(CH3)2](0CH2-CF3) IAa.391 H -P(=O)[N(CH3)2](0CH2-CO-OCH3) ~- IAa.392 H -P(=O)[N(CH3)2](0CH2-CO-OC2H5) IAa.393 H -P(=O)(NH-CH2-CH2-O) IAa.394 H -P(=O)(NH-CH2-CH2-NH) IAa.395 H -P(=O)[N(CH3)-CH2-CH2-N(CH3)]
IAa.396 H -P(=O)(NH-CH2-CH2-CH2-O) IAa.397 H -P(=O)(NH-CH2-CH2-CH2-NH) IAa.398 H -P(=O)[N(CH3)-CH2-CH2-CH2-N(CH3)]
25 IAa.399 H -P(=O)[O-CH2-CH(CH3)-cH2-O]
IAa.400 H -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.401 H -P(=O) N(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.402 H -P(=O) NH-CEI2-CH2-CH2-CH2-O]
IAa.403 H -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.404 H -P(=S)~NH2)2 IAa.405 H -P(-S)~NH-CH3)2 CIAa.406 H -P(=S)~N(CH3)2]2 IAa.407 H -P(=S)~NH-C2Hs)2 35 IAa.408 H -P(=S)[N(C2Hs)2]2 IAa.409 H -P(=S)(NH-CH2-CH2-CH2-O) IAa.410 H -P(=S)(NH-CE~2-CH2-CH2-NH) IAa.411 H -P(=S)[N(CH3)-CH2-CH2-CH2-N(CH3)]
40 IAa.412 H -P(=O)(SCH3)2 IAa.413 H -P(=O)(SC2Hs)2 IAa.414 H -P(=O) S-(n-C3H7)]2 IAa.415 H --P(=O) SCH(CH3)2]2 IAa.416 H -P(=O) S-(n-~Hs)]2 IAa.417 H -P(=O)(SCH2-CH=CH2)2 LAa.418 H -P(=O)(S-phenyl~2 0050/46~86 CA 0224~6~9 l998-08-06 .
No. R4 P(=Yl)(Y2Rl)(Y3RZ) LAa.419 H -P(=O)(ScH2-phenyl~2 IAa.420 H -p(=o)(scH2-co-ocH3)2 5 LAa.421 H -p(=o)(scH2-co-oc2Hs)2 LAa.422 H -p(=o)(s-cH2-cH2-cH2-s) IAa.423 H -P(=O)(S-CHz-CH2-CH2-O) IAa.424 H -P(=S)(SCH3)2 IAa.425 H -P(=S)(SCzHs)2 IAa.426 H -P(=S)[S-(n-CaH7)]2 IAa.427 H -P(=S)~S-n-~Hs)]2 LAa.428 H -P(=S)(S-CH2-CH2-CH2-S) IAa.429 H -P(=S)(S-CHz-CH2-CH2-O) 15 IAa.430 Cl _p(=o)(oH)2 -~ IAa.431 Cl _p(=O)(OCH3)2 ~IAa.432 Cl -P(=o)(oc2Hs)2 IAa.433 Cl _p(=O)[O-(n-~H7)]2 20 IAa.434 Cl _p(=O)[OCH(CH3)2]2 IAa.435 Cl _p(=o) ~-(n-~Hs)]2 LAa.436 Cl -P(=O) OCH2-CH(CH3)2]2 LAa.437 Cl -P(=O) OCH(CH3)-C2H5]2 25 IAa.438 Cl _p(=O)(OCH2-CF3)2 LAa.439 Cl -P(=O)(OCH2-CH2-OH~2 IAa.440 Cl _p(=O)(OCH2-CH2-CN~2 IAa.441 Cl -P(=O)(OCH2-CH2-OCH3)2 IAa.442 Cl -P(=O)(OCH2-CH2-OC2H5)2 30 IAa.443 Cl -P(=O)(OCH2-CH2-OCF3)2 f~ IA~.444 Cl -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 ~- IAa.445 Cl -P(=O)(OCH2-CH2-OCH2-C----CH)2 IAa.446 Cl -P(=O)(OCH2-CH2-O-cyclopentyl~
35 L~a.447 Cl -p(=o)(ocH2-cH2-NH2)2 IAa.448 Cl -P(=O)(OCH2-CH2-NH-CH3)2 LAa.449 Cl -P(=O)[OCH2-CH2-N(CH3)2]2 IAa.450 Cl _p(=o)(ocH2-cH2-scH3)2 40 L~a.451 Cl -P(=O)(OCH2-CH2-SC2H5)2 IAa.452 Cl -P(=O)(OCH2-CH2-SCF3)2 IAa.453 Cl -P(=O)(OCH2-CH2-SCH2-CH=CH2)2 IAa.454 Cl -P(=O)(OCH2-CH2-SCH2-C----CH)2 45 IAa.455 Cl -P(=O)(OCH2-CH2-SO-CH3)2 -IAa.456 Cl -P(=O)(OCH2-CH2-SO-C2H5)2 IAa.457 Cl _p(=O)(OCH2-SO2-CH3)2 0050/46586 CA 02245659 l998-08-06 No. R4 --p(=yl)(Y2R1)(Y3R2) LAa.458 Cl -P(=O)(OCH2-SO2-C2Hs)2 IAa.459 Cl -P(=O)(OCH2-CH2-S02-CH3)2 LAa.460 Cl -P(=O)(OCH2-CH2-S02-C2Hs)2 LAa.461 Cl -P(=O)(OCH2-CH=CH2)2 IAa.462 Cl -P(=O)(OCH2-CH=CH-CH3)2 IAa.463 Cl --P(=O)(OCH2-CH2-CH=CH2)2 IAa.464 Cl -P(=O)(OCH2-CH=CH-Cl~Q
IAa.465 Cl -P(=O)(OCH2-C--CH)2 IAa.466 Cl _p(=o)[ocH(cH3)-c--CH]2 IAa.467 Cl -P(=O)(OCH2-CO-OCH3)2 IAa.468 Cl -P(=O)(OCH2-CO-OC2H5)2 IAa.469 Cl -P(=O) OCH(CH3)-CO-OCH3]2 ,~ IAa.470 Cl -P(=O) OCH(CH3)-CO-OC2H5]2 IAa.471 Cl _p(=O)(OCH2-CO-N~2)2 IAa.472 Cl --P(=O)(OCH2-CO-NH-C~3)2 IAa.473 Cl --P(=O)[OCH2-CO-N(CE~3)2]2 IAa.474 Cl -P(=O)[OCH(CH3)-CO-N~2]2 IAa.475 Cl --P(=O) OcH(cH3)-co-NH-cE~]2 IAa.476 Cl -P(=O) OCH(CH3)-CO-N(CH3)2]2 25 IAa.477 Cl -P(=O)(O-cyclopropyl~e IAa.478 Cl -P(=O)(O-cyclobutyl~z IAa.479 Cl -P(=O)(O-cyclopentyl~e IAa.480 Cl --P(=O)(O-cyclohe~yl~2 IAa.481 Cl -p(=o)(ocH2-cyclopropyl)2 IAa.482 Cl -P(=O)(OCH2--cyclobutYl)2 r.IAa.483 Cl --p(=o)(ocH2-cydopentyl~2 IAa.484 Cl -p(=o)(ocH2-cyclohexyl)2 IAa.485 Cl --P(=O)(O-phenyl~Q
3 5 IAa.486 Cl --P(=O)(OCH2--phenyl)2 IAa.487 Cl -P(=O)(O-oxetan-3-yl~
IAa.488 Cl -P(=O)(O-tetrahyd.oru~ -2--yl~
IAa.489 Cl -P(=O)(O-tetrahydrofuran-3-yl~
40 IAa.490 Cl -P(=O)(O-tetral ydlopyldn-2-yl~
IAa.491 Cl -P(=O)(O-tetral.ydl o~y I an-3-yl~
IAa.492 Cl -P(=O)(O-tetrahydlo~.yl~l-4-yl~
IAa.493 Cl -P(=O)(OCH2-oxiran-2-yl~
IAa.494 Cl -P(=O)(OCH2-oxetan-3-yl~?
IAa.495 Cl -P(=O)(OCH2-tetrah~dlorulaJl-2-yl~
IAa.496 Cl -P(=O)(OCH2-tetrahydrofuran-3-yl~
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 -p(=yl)(y2Rl)(y3R2) IAa.497 Cl -P(=O)(OCH2-pyrrolidin-l-yl~
IAa.498 Cl -P(=O)[OCH2-(2-py~olidon-l-yl)~
5 IAa.499 Cl -P(=O)(OCH2-tetrahyd,o~y.an-2-yl~
IAa.S00 Cl -P(=O)(OCH2-tetrahy~o~yldn-3-yl~
IAa.501 Cl -p(=o)(ocH2-tetrahyd,o~y,an-4 IAa.502 Cl -P(=O)(OCH2-piperidin-l-yl~
L~a.503 Cl -P(=O)(OCH2-morpholin-4-yl~
IAa.504 Cl -P(=O)(OH)(OCH3) IAa.505 Cl -P(=O)(OH)(OC2Hs) IAa.506 Cl -P(=O)(OH)[O-[n-C3H7) IAa.507 Cl _P(=O)(OH) OCH(CH3)2 15 IAa.508 Cl -P(=O)(OH) O-(n-~Hs)~
.J-IAa.509 Cl -P(=O)(OH) OCH2-CH(CH3)2]
L~a.510 Cl -P(=O)(OH) OCH(CH3)-C2Hs]
IAa.511 Cl _p(=O)(OH)(OCH2-CF3) 20 IAa.512 Cl -P(=O)(OH)(OCH2-CH2-OH) IAa.513 Cl -P(=O)(OH)(OCH2-CH2-CN) IAa.514 Cl -P(=O)(OH)(OCH2-CH2-OCH3) IAa.515 Cl -P(=O)(OH)(OCH2-CH2-OC2Hs) IAa.516 Cl -P(=O)(OH)(OCH2-CH2-OCF3) IAa.517 Cl -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) IAa.518 Cl -P(=O)(OH)(OCH2-CH2-OCH2-C-- CH) IAa.Sl9 Cl -P(=O)(OH9(0CH2-CH2-O-cyclopentyl) IAa.520 Cl -P(=O)(OH)(OCH2-CH2-NH2) IAa.521 Cl -P(=O)(OH)(OCH2-CH2-NH-CH3) f_IAa.522 Cl -P(=O)(OH)~OCH2-CH2-N(CH3)2]
IAa.523 Cl -P(=O)(OH)(OCH2-CH2-SCH3) IAa.524 Cl -P(=O)(OH)(OCH2-CH2-SC2HS) 35 IAa.525 Cl -P(=o)(oH)(ocH2-cH2-scF3) IAa.526 Cl -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.527 Cl -P(=O)(OH)(OCH2-CH2-SCH2-C-- CH) IAa.528 Cl -P(=O)(OH)(OCH2-CH2-SO-CH3) 40 IAa.529 Cl -P(=O)(OH)(OCH2-CH2-SO-C2Hs) IAa.530 Cl -P(=O)(OH)(OCH2-SO2-CH3) IAa.531 Cl -P(=O)(OH)(OCH2-SO2-C2Hs) IAa.532 Cl -P(=O)(OH)(OCH2-CH2-SO2-CH3) IAa.533 Cl -P(=o)(oH)(ocH2-cH2-so2-c2Hs) IAa.534 Cl -P(=O)(OH)(OCH2-CH=CH2) IAa.535 Cl -P(=O)(OH~(OCH2-CH=CH-CH3) 0050/46586 CA 0224~6~9 1998-08-06 No. R4 _p(=y1)(Y2Rl)(Y3R2) IAa.536 Cl -P(=O)(OH)(OCH2-CH2-CH=cH2) IAa.537 Cl -P(=O)(OH)(OCH2-CH=CH-Cl) 5 IAa.538 Cl -P(=O)(OH)(OCH2-C--CH) IAa.539 Cl -P(=O)(OH)tOCH(CH3)-C_ CH]
IAa.540 Cl -P(=O)(OH)(OCH2-CO-OCH3) IAa.541 Cl --P(=O)(OH)(OCHz-CO-OC2Hs) IAa.542 Cl -P(=O)(OH)[OCH(CH3)-CO-OCH3]
IAa.543 Cl -P(=O)(OH)[OCH(CH3)-CO-OC2Hs]
IAa.544 Cl --P(=o)(oH)(ocH2-co-N~2) IAa.545 Cl -P(=O)(OH)(OCH2-CO-NH-CH3) IAa.546 Cl -P(=O)(OH)[OCH2-CO-N(CH3)2]
15 IAa.547 Cl -P(=O)(OH)[OCH(CH3)-CO-NH2]
' IAa.548 Cl -P(=O)(OH)[OCH(CH3)-CO-NH-CH3]
IAa.549 Cl _p(=O)(O~[OCH(CH3)-CO-N(CH3)2]
IAa.550 Cl --P(=O)(OEl)(O-cyclopropyl) 20 IAa.551 Cl -P(=O)(OH)(O-cyclobutyl) IAa.552 Cl --P(=O)(OH)(O-cyclopentyl) IAa.553 Cl -P(=O)(OH)(O-cyclohe~yl) IAa.554 Cl -P(=O)(OH)(OCH2-cydop}opyl) 2 5 IAa.SSS Cl -P(=O)(OH)(OCH2-cyclobutyl) LAa.556 Cl -P(=O)(OH)(OCH2-cyclopentyl) IAa.557 Cl -P(=O)(OH)(OCH2-cyclohexyl) IAa.558 Cl -P(=O)(OH)(O-phenyl) IAa.SS9 Cl -P(=O)(OH)(OCH2-phenyl) IAa.560 Cl --P(=O)(OH)(O-oxetan-3-yl) fIAa.561 Cl -P(=O)(OH)(O-tetrahy-h~/ru.all-2-yl) ;~--IAa.562 Cl -P(=O)(OH)(O-tetrahyd.oru~ -3-yl) IAa.563 Cl --P(=O)(OH)(O-tetraLyd~ol,y~a-~-2-yl) 35 IAa.564 Cl -P(=O)(OH)(O-tetrahyd.~,~ylan-3-yl) IAa.565 Cl -P(=O)(OH)(O-tetrahyd o~y-dn-4-yl) IAa.566 Cl -P(=O)(OH)(OCH~-o~iran-2-yl) IAa.567 Cl -P(=O)(OH)(OCH2-oxetan-3-yl) 40 IAa.568 Cl -P(=O)(OH)(OCH2--tetrahyd.oru.~.n-2-yl) IAa.569 Cl -P(=O)(OH)(OCH2-tetrahyd oL.an-3-yl) IAa.570 Cl --P(=O)(OH)(OCH2-pyrrolidin-1--yl) IAa.571 Cl -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
45 IAa.572 Cl -P(=O)(OH)(OCH2-tetrahyd~opy.dll-2-yl) IAa.573 Cl --P(=O)(OH)(OCH2--tetrahy~l.o~y~dn-3-yl) IAa.574 Cl --P(=O)(OH)(OCH2-tetraLy.l.o~y.an-4-yl) 0050/46586 CA 0224~6~9 1998-08-06 o No. R4 _p(=yl)cy2Rl)(y3R2) IAa.575 Cl -P(=O)(OH)(OCH2-piperidin-l-yl) LAa.576 Cl -P(=O)(OH)(OCH2-morpholin-4-yl) 5 IAa.577 Cl _p(=o)(ocH3)(oc2H5) IAa.578 Cl -p(=o)(ocH3)[o-(n-c3H7)]
IAa.579 Cl _p(=o)(OCH3)[0CH(CH3)2]
IAa.580 Cl ~P(=o)(ocH3)[o-(n-c4H9)]
IAa.581 Cl -P(=O)(OCH3)[OCH2-CH(CH3)2]
IAa.582 Cl -P(=o)(ocH3)[ocH(cH3)-c2Hs]
L~a.583 Cl _p(=o)(ocH3)(ocH2-cF3) IAa.584 Cl -P(=O)(OCH3)(OCH2-CH2-OH) IAa.585 Cl -P(=O)(OCH3)(0CH2-CH2-CN~
15 IAa.586 Ci -P(=O)(OCH3)(OCH2-CH2-OCH3) ~~IAa.587 Cl ~p(=o)(ocH3)(ocH2-cH2-oc2Hs) IAa.588 Ci -P(=O)(OCH3)(OCH2-CH2-OCF3) IAa.589 Cl -p(=o)(ocH3)(ocH2-cH2-ocH2-cH=cH2) 20 IAa.590 Ci -P(=O)(OCH3)(0CH2-CH2-OCH2-C-- CH~
IAa.591 Cl -P(=O)(OCH3)(OCH2-CH2-O-cyclopentyl) IAa.592 Cl -P(=O)(OCH3)(OCH2-CH2-NH2) IAa.593 Ci -P(=O)(OCH3)(OCH2-CH2-NH-CH3) 25 L~a594 Cl -p(=o)(ocH3)[ocH2-cH2-N(cH3)2]
IAa.S9S Ci -P(=O)(OCH3)(OCH2-CH2-SCH3) IAa.596 Ci -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.597 Ci -P(=O)(OCH3)(OCH2-CH2-SCF3) IAa.598 C~ -p(=o)(ocH3)(ocH2-cH2-scH2-cH=cH2) IAa.S99 Cl -P(=O)(OCH3)(0CH2-CH2-SCH2-C----CH) f~IAa.600 Ci -P(=O)(OCH3)(OCH2-CH2-SO-CH3) '--L~a.601 Ci -p(=o)(ocH3)(ocH2-cH2-so-c2Hs) IAa.602 Ci -P(=o)(ocH3)(ocH2-soz-cH3) 35 IAa.603 Ci -P(=O)(OCH3)(OCH2-SO2-C2Hs) IAa.604 Cl -P(=O)(OCH3)(OCH2-CH2-SO2-CH3) IAa.605 Ci -P(=O)(OCH3)(OCH2-CH2-SO2-C2Hs) IAa.606 Ci -P(=o)(ocH3)(ocH2-cH=cH2) 40 IAa.607 Ci -P(=O)(OCH3)(OCH2-CH=CH-CH3) IAa.608 Ci -P(=O)(OCH3)(OCH2-CH2-CH=CH2) IAa.609 Cl -P(=O)(OCH3)(OCH2-CH=CH-Ci) IAa.610 Ci -P(=O)(OCH3)(OCH2-C- CH) IAa.611 Ci --P(=O)(OCH3)[0CH(CH3)-C--CH]
IAa.612 Cl -P(=O)(OCH3)(OCH2-CO-OCH3) IAa.613 Ci -P(=O)(OCH3)(OCH2-CO-OC2Hs) 0050/46586 CA 0224~6~9 1998-08-06 No. R4 --p(=yl)(Y2R1)(Y3R2) L4a.614 Cl -P(=O)(OCH3)[0CH(CH3)-CO-OCH3]
IAa.615 Cl -P(=O)(OCH3)[0CH(CH3)-CO-OC2Hs]
L~a.616 Cl -p(=o)(ocH3)(ocH2-co-N~2) IAa.617 Cl -P(=O)(OCH3)(0CH2-CO-NH-C~) IAa.618 Cl -P(=O)(OCH3) 0CH2-CO-N(CH3)2]
IAa.619 Cl -P(=O)(OCH3) OCH(CH3)-CO-NEI2~
IAa.620 Cl -P(=O)(OCH3) OCH(CH3)-CO-NH-CE~]
IAa.621 Cl -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.622 Cl -P(=O)(OCH3)(0-cyclopropyl) IAa.623 Cl -P(=O)(OCH3)(0-cyclobutyl) IAa.624 Cl --P(=O)(OCH3)(0-cyclopentyl) IAa.625 Cl -P(=O)(OCH3)(0-cyclohe~yl) f: IAa.626 Cl -P(=O)(OCH3)(0CH2-cydopropyl) L4a.627 Cl -P(=O)(OCH3)(0CH2-cyclobutyl) IAa.628 Cl -P(=O)(OCH3)(0CH2-cyclopentyl) L4a.629 Cl -P(=O)(OCH3)(0CH2-cyclohexyl) IAa.630 Cl -P(=O)(OCH3)(0-phenyl) IAa.631 Cl -P(=O)(OCH3)(0CH2-phenyl) IAa.632 Cl -P(=O)(OCH3)(0-oxetan-3-yl) 2 5 IAa.633 Cl -P(=O)(OCH3)(0-tetrahylL Oru. an-2-yl) LAa.634 Cl -P(=O)(OCH3)(0-tetral yd.vrulall-3-yl) IAa.635 Cl -P(=O)(OCH3)(0-tetrallyd o~yl~-2-yl) IAa.636 Cl -P(=O)(OCH3)(0-tetrahydlv~,y.dn-3-yl) IAa.637 Cl -P(=O)(OCH3)(0-tetrahy d. ~y. dn-4--yl) IAa.638 Cl -P(=O)(OCH3)(0CH2-o~iran-2-yl) ~_ IAa.639 Cl -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.640 Cl -P(=O)(OCH3)(0CH2-tetrahydrofuran--2--yl) IAa.641 Cl -P(=O)(OCH3)(0CH2-tetrally~;Lvru.~-3-yl) 3 5 IAa.642 Cl -P(=O)(OCH3)(0CH2-pyrrolidin-1-yl) IAa.643 Cl -P(=O)(OCH3)[0CH2-(2-pyrrolidon-1-yl)]
IAa.644 Cl --P(=O)(OCH3)(0CH2-tetraLy~Lvl,y.d.l-2-yl) IAa.645 Cl -P(=O)(OCH3)(0CH2-tetrahyd.vpy.dn-3-yl) IAa.646 Cl -P(=O)(OCH3)(0CH2-tetrahy~v~.y.dll~-yl) IAa.647 Cl -P(=O)(OCH3)(0CH2-piperidin--1--yl) IAa.648 Cl -P(=O)(OCH3)(0CH2-morpholin-4-yl) IAa.649 Cl -P(=O)(oc2Hs)[o-(n-c3H7)]
IAa.650 Cl -P(=o)(oc2Hs)[ocH(cH3)2]
IAa.651 Cl --P(=~)(~C2Hs)[~-(n-ciHs)]
IAa.652 Cl -P(=o)(oc2Hs)[ocH2-cH(cH3)2]
0050/46586 CA 0224~6~9 1998-08-06 ~ . . .
No. R4 --P(=Yl)CY2Rl)~y3R2) LA a.653 Cl -P(=O)(OC2H5)[0CH(CH3)-C2H5]
5LAa.654 Cl -P(=o)(oc2Hs)(ocH2-cF3) LAa.655 Cl -P(=O)(OC2Hs)(OCH2-cH2-OH) LAa.656 Cl -P(=O)(OC2Hs)(OCH2-CH2-C~
LA~.657 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCH3) 10LAa.6$8 Cl -P(=O)(OC2Hs)(OCH2-CH2-OC2H5) LAa.659 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCF3) I~a.660 Cl --P(=O)(OC2Hs)(ocH2-cH2-ocH2-cH=cH2) I~a.661 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCH2-C--CH) LAa.662 Cl -P(=O)(OC2Hs)(OCH2-CH2-O-cyclopentyl) I~a.663 Cl -P(=o)(oc2Hs)(ocH2-cH2-NH2) LAa.664 Cl -P(=O)(OC2Hs)(OCH2-CH2-NH-CH3) LAa.665 Cl -P(=o)(oc2Hs)[ocH2-cH2-N(cH3)2]
LAa.666 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH3) 20LAa.667 Cl -P(=O)(OC2H5)(0CH2-CH2-SC2H5) LAa.668 Cl -P(=O)(OC2Hs)(OCH2-CH2-SCF3) I~a.669 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH2-CH=CH2) LAa.670 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH2-C----CH) 25LAa.671 c~ -P(=O)(OC2H5)(0CH2-CH2-SO-CH3) LAa.672 Cl -P(=O)(OC2Hs)(OCH2-CH2-SO-C2H5) LAa.673 Cl -P(=O)(OC2Hs)(OCH2-SO2-CH3) LAa.674 Cl --P(=O)(OC2H5)(0CH2--S02 - c2H5) 30LAa.675 Cl -P(=O)(OC2Hs)(OCH2-CH2-SO2-CH3) LAa.676 Cl -P(=O)(OC2H5)(0CH2-CH2-SO2-C2H5) -- LAa.677 Cl -p(=O)(OC2H5)(0CH2-CH=cH2) a.678 Cl -P(=O)(OC2H5)(0CH2-CH=CH-CH3) LAa.679 Cl -P(=o)(oc2H5)(ocH2-cH2-cH=cH2) 35LAa.680 Cl -P(=O)(OC2H5)(0CH2-CH=CH-Cl) LAa.681 Cl -P(=O)(OC2H5)(0CH2-C2 CH) LAa.682 Cl -P(=O)(OC2H5)[0CH(CH3)-C--CH]
LAa.683 Cl -P(=O)(OC2H5)(0CH2-CO-OCH3) 40I~a.684 Cl -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~a.685 Cl -P(=O)(OC2H5)[0CH(CH3)-CO-OCH3]
LAa.686 Cl --P(=O)(OC2H5)[0CH(CH3)--CO--OC2H5]
I~a.687 Cl -P(=O)(OC2H5)(0CH2-CO-NH2) 45I~a.688 Cl -P(=O)(OC2H5)(0CH2-CO-NH-C~) I~a.689 Cl -P(=O)(OC2H5) OcH2-co-N(cH3)2]
LAa.690 Cl --P(=O)(OC2HS) OCH(CH3)-CO--N~2]
, 48 _ No. R4 _p(=yl)(y2R1)~y3R2) IAa.691 Cl -P(=O)(OC2Hs)[OCH(CH3)-CO-NH-C~g]
L~a.692 Cl -P(=O)(OC2Hs)[OCH(CH3)-CO-N(CH3)2]
5 IAa.693 Cl -P(=O)(OC2Hs)(O-cyclopropyl) L~a.694 C~ -P(=O)(OC2Hs)(O-cyclobutyl) IAa.695 Cl -P(=O)(OC2Hs)(O-cyclopentyl) L~a.696 Cl -P(=O)(OC2Hs)(O-cyclohexyl) IAa.697 Cl -P(=o)(oc2Hs)(ocH2-cyclopropyl) IAa.698 Cl -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.699 Cl -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa.700 Cl -P(=O)(OC2Hs)(oCH2-cydohe~yl) LAa.701 - Cl ~P(=O)(~C2Hs)(O-phenyl) 15 IAa.7o2 Cl ~P(=o)(oc2Hs)(ocH2-phenyl) IAa.703 Cl -P(=O)(OC2Hs)(O-o~etan-3-yl) L~a.704 Cl -P(=O)(OC2Hs)(O-tetrahy~oruldn-2-yl) IAa.705 Cl -P(=O)(OC2Hs)(O-tetrahy~oru-d~-3-yl) 20 LAa.706 Cl -P(=O)(OC2Hs)(O-tetrahy~o~ylan-2-yl) IAa.707 Cl -p(=o)(oc2Hs)(o-tetrahy~o~ylan-3-yl) LQa.708 Cl -P(=O)(OC2Hs)(O-tetrahy~o~ylan-4-yl) LAa.709 Cl -P(=O)(OC2Hs)(OCH2-o~ran-2-yl) 25 IAa.710 Cl -P(=O)(OC2Hs)(OCH2-oxetan-3-yl) IAa.711 Cl -P(=O)(OC2Hs)(OCII2 t~tlohy~orulan-2-yl) IAa.712 Cl -P(=O)(OC2Hs)(OCH2-tetrahydrofuran-3-yl) IAa.713 Cl -P(=O)(OC~Hs)(OCH2-py~olidin-l--yl) IAa.714 Cl -P(=O)(OC2Hs)[OCH2-(2-py~olidon-1-yl)]
IAa.715 Cl -P(=O)(OC2Hs)(OCH2-tetrahy~u,uylan-2-yl) ~,IAa.716 C~ -P(=O)(OC2Hs)(OCH2-tetrahy&u~ldn-3-yl) i LAa.717 C~ -P(=O)(OC2Hs)(OCII2 t~h~hy~u~yl~n-4-yl) IAa.718 Cl -P(=O)(OC2Hs)(OCH2-piperidin-1-yl) 35 IAa.719 Cl -P(=O)(OC2Hs)(OCH2-morpholin-4-yl) IAa.720 Cl _p(=o)(l~2-phenylen~Ai~yy) IAa.721 C~ _p(=o)(o-cH2-cH2-o) IAa.722 Cl -P(=O)[O-CH(CH3)-CH2-O]
40 IAa.723 Cl -P(=O)[O-CH(CHO-CH(CH3)-O]
IAa.724 Cl -P(=O)[O-CH(COOC~O-CH(COOCH3)-O]
IAa.725 Cl -P(=O)(O-CH2-CH2-cH2-O) IAa.726 Cl -P(=O)[O-CH2-C(CH3)2-cH2-O]
45 IAa.727 Cl -P(=o)(o-cH2-cH2-cH2-cH2-o) IAa.728 Cl -P(=S)(OH~2 IAa.729 C~ -P(=S)(OCH3)2 .
49 _ No. R4 --p(=yl)(y2Rl)(y3R2) IAa.730 Cl -P(=S)(OC2H5)2 IAa.731 Cl -P(=S)lO-(n-C3H7)]2 5 IAa.732 Cl ~P(=s)[o-(n-ctHs)]2 IAa.733 Cl -P(=S)(O-CE~2-CH2-CH2-O) IAa.734 Cl _p(=O)(NH2)2 IAa.735 Cl _p(=O)(NH-CH3)2 IAa.736 Cl _P(=O)LN(CH3)2]2 IAa.737 Cl ~P(=o)(NH-c2Hs)2 IAa.738 Cl _p(=~)[N(C2H5)2]2 IAa.739 Cl -P(=O)(NH-CEI2-CH=CH2)2 IAa.740 Cl -p(=O)(NH-c~2-c----CH)2 15 IAa.741 Cl -P(=O)(NH-cyclopropyl~z ~-IAa.742 Cl -p(=o)(NH-cH2-cyclopentyl~2 IAa.743 Cl ~p(=o)(NH-phenyl~2 IAa.744 Cl -P(=O)(NH-CH2-phenyl~2 20 IAa.745 Cl -P(=O)(pyrrolidin-1-yl~
IAa.746 Cl -P(=0)(2-methu~y~l,onyl~y~olidin IAa.747 Cl -P(=O)(NH-CH2-CO-OC~)2 IAa.748 Cl -P(=O)~N(CH3)-CH2-CO-OC~]2 IAa.749 Cl -P(=O)(NH-CH2-CO-OC2Hs)2 ~a.750 Cl -P(=O) N(CH3)-CH2-CO-OC2Hs 2 IAa.751 Cl -P(=O) NH-CH(CH3)-CO-OcH3: 2 IAa.752 Cl -P(=O)(OH)(NH2) IAa.753 Cl -P(=O)(OH)(NH-CEO
IAa.754 Cl _p(=O)(OH)[N~CH3)2]
,_ IAa.755 Cl _p(=o)(oH)(NH-c2Hs) - IAa.756 Cl _p(=O)(OH)tN(c2H5)2]
IAa.757 Cl --P(=O)(OH){NH-CH2-CH=CH2) 3 5 IAa.758 Cl --P(=O)(OH)(NH-CH2-C_ CH) IAa.759 Cl --P(=O)(OH)(NH-cyclopropyl) IAa.760 Cl -P(=O)(OH)(NH-C~2-cyclopentyl) IAa.761 Cl --P(=O)(OH)(NH-phenyl) 40 IAa.762 Cl -P(=O)(OH)(NH-CH2-phenyl) IAa.763 Cl -P(=O)(OH)(pyrrolidin-1-yl) IAa.764 Cl -P(=O)(OH)(2-metho~y~.l,ol.yll,yl.ùlidin-1-yl) IAa.765 Cl -P(=O)(OH)(NH-C~2-CO-OC~3) IAa.766 Cl -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
IAa.767 Cl -P(=O)(OH)(NH-CE~-CO-OC2Hs) IAa.768 Cl -p(=o)(oH)[N(cH3)-cH2-co-oc2Hs]
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)~y2Rl)(y3R2) _ IAa.769 Cl -P(=O)(OH)[NH-CH(CH3)-CO-OCE~3]
IAa.770 Cl _p(=O)(OCH3)(NH2) 5 IAa.771 Cl -P(=O)(OCH3)(NH-CH3) IAa.772 Cl _p(=O)(OCH3)[N(CH3)2]
IAa.773 Cl -P(=o)(ocH3)(NH-c2Hs) IAa.774 Cl _p(=o)(OCH3)[N(C2Hs)2]
IAa.775 Cl --P(=O)(OCH3)(NH-CH2-CH=CH2) IAa.776 Cl -P(=O)(OCH3)(NH-CH2-C--CH) IAa.777 Cl -P(=O)(OCH3)(NH-cyclopropyl) IAa.778 Cl -P(=O)(OCH3)(NH-CH2-cyclopentyl) IAa.779 Cl -P(=O)(OCH3)(NH-phenyl) 15 IAa.780 Cl -P(=O)(OCH3)(NH-CH2-phenyl) f; IAa.781 Cl -P(=O)(OCH3)(pyrrolidin-1-yl) ;~ IAa.782 Cl -P(=O)(OCH3)(2-metho~ycarbo~yl~y.. ~lidin-1-yl) IAa.783 Cl -P(=O)(OCH3)~NH-CH2-CO-OCE~3) 20 IAa.784 Cl -P(=O)(OCH3)[N(CH3)-CH2-CO-OCH3]
IAa.785 Cl -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.786 Cl -p(=o)(ocH3)[N(cH3)-cH2-co-oc2Hs]
IAa.787 Cl -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
25 IAa.788 Cl -P(=O)(OC2Hs)(NH2) IAa.789 Cl -P(=o)(oc2Hs)(NH-cH3) IAa.790 Cl -P(=O)(OC2Hs)[N(cH3)2]
IAa.791 Cl -P(=o)(oc2Hs)(NH-c2H5) IAa.792 Cl _p(=o)(oc2Hs)[N(c2Hs)2]
IAa.793 Cl -p(=o)(oc2Hs)(NH-cH2-cH=cH2) IAa.794 Cl ~P(=o)(oc2Hs)(NH-cH2-c--CH) IAa.795 Cl -P(=O)(OC2Hs)(NH-cyclopropyl) IAa.796 Cl -P(=O)(OC2Hs)(NH-CH2-cyclopentyl) 3 5 IAa.797 Cl ~P(=O)(oc2Hs)(NH-phenyl) IAa.798 Cl -P(=O)(OC2Hs)(NH-CH2-phenyl) IAa.799 Cl ~P(=o)(oc2Hs)(pyrrolidin-l-yl) IAa.800 Cl -P(=O)(OC2Hs)(2-methoxycarb~ yl~,y.. olidin-1-yl) 40 IAa~801 Cl -P(=O)(OC2Hs)(NH-CH2--CO-OCH3) IAa.802 Cl -P(-O)(OC2Hs)tN(CH3)-CH2-CO-OCH3]
IAa.803 Cl -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.804 Cl -P(=O)(OC2Hs)[N(CH3)-cH2-cO-oc2H5]
45 IAa.805 Cl -P(=O)(OC2Hs)[NH-CH(CH3)-CO-OC~I3]
IAa.806 Cl --P(=O)rN(CH3)2~(OCH3) IAa.807 Cl -P(=o)tN(cH3)2](oc2H5) CA 02245659 l998-08-06 51 _ No. R4 _p(=y1)(Y2R1)(Y3R2) IAa.808 Cl _p(=O)[N(CH3)2] ~~(n~C3H7)]
IAa.809 Cl -P(=O)[N(CH3)2] OCH(CH3)2]
IAa.810 Cl _p(=O)[N(CH3)2] O-(n-ciH9)]
IAa.811 Cl -P(=O) N(cH3)2(ocH2-cH=cH2) IAa.812 Cl -P(=O) N(CH3)2(OCH2-Ce CH) IAa.813 Cl -P(=O) N(CH3)2(O-cyclohe~yl) IAa.814 Cl -P(=O) N(CH3)2(OCH2-cyclohe~yl) IAa.815 Cl -P(=O) N(CH3)2(O-phenyl) IAa.816 Cl -P(=O) N(CH3)2(OCH2-phenyl) IAa.817 Cl -P(=O)[N(CH3)2](O-tetra~y~fulan-2-yl) IAa.818 Cl -P(=O)~N(CH3)2](0CH2-o~etan-3-yl) 15 IAa.819 Cl -P(=O)LN(CH3)2](OCH2-CF3) IAa.820 Cl -P(=O)[N(CH3)2](OCH2-CO-OCH3) ~IAa.821 Cl -P(=O)[N(CH3)2](OCH2-CO-OC2Hs) IAa.822 Cl -P(=O)~NH-CH2-CH2-O) 20 IAa.823 Cl -P(=O)~NH-CH2-CH2-NH) IAa.824 Cl -P(=O)[N(CH3)-CHz-CH2-N(CH3)]
IAa.825 Cl -P(=O)~NH-CH2-CH2-CH2-O) IAa.826 Cl -P(=O)(NH-CHz-CH2-CH2-NH) 25 IAa.827 Cl -P(=O)[N(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.828 Cl -P(=O)(O-CH2-CH(CH3)-cH2-O) IAa.829 Cl -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.830 C~ -P(=O) N(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.831 Cl -P(=O)NH-CH2-CH2-CH2-cH2-O]
3 IAa.832 Cl -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.833 Cl _P(=s)~H2)2 IAa.834 Cl -P(=s)(NH-cH3)2 IAa.835 Cl -P(=S)[N(CH3)2]2 35 IAa.836 Cl -P(=S)(NH-C2Hs)2 IAa.837 Cl -P(=S)[N(C2Hs)2]2 IAa.838 Cl -P(=S)(NH-CH2-CH2-CH2-O) IAa.839 Cl -P(=S)(NH-CH~-CH2-CH2-NH) IAa840 Cl -P(=S)tN(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.841 Cl _p(=O)(SCH3)2 IAa.842 Cl ~P(=~)(SC2Hs)2 IAa.843 Cl _p(=o)[s-(n-caH7)]2 IAa.844 Cl _p(=O)[SCH(CH3)2]2 IAa.845 Cl -P(=O)~S-(n-~Hs)]2 IAa.846 Cl _p(=o)(scH2-cH=cH2)2 CA 0224~6~9 1998-08-06 No. R4 _p(=y1)(Y2Rl)(Y3R2) IAa.847 Cl -P(=O)(S-phenyl~2 L~a.848 Cl -p(=o)(scH2-phenyl~2 IAa.849 Cl -P(=o)(scH2-co-ocEO2 IAa.850 Cl -P(=O)(SCH2-CO-OC2H5)2 IAa.851 Cl -P(=O)(S-CE~2-CH2-CH2-S) IAa.852 Cl -P(=o)(s-c~2-cH2-cH2-o) IAa.853 Cl -P(=S)(SCH3)2 IAa.854 Cl -P(=S)(SC2H5)2 L~a.855 Cl -P(=S)[S-(n-C3H7)]2 IAa.856 Cl -P(=S)[S-n-C~Hs)]2 IAa.857 Cl -p(=s)(s-cEI2-cH2-cH2-s) IAa.858 Cl -P(=S)(S-CH2-CH2-CH2-O) IAa.859 F -P(=O)(OH)2 L~a.860 F -P(=O)(OcH3)2 IAa.861 F -P(=O)(Oc2H5)2 IAa.862 F -P(=O)[O-(n-C3H~)]2 IAa.863 F -P(=O)[OCH(CH3)2]2 IAa.864 F -P(=O)[O-(n-~Hg)]2 IAa.865 F -p(=o)[ocH2-cH(cH3)2 2 IAa.866 F -p(=o)[ocH(cH3)-c2Hs 2 IAa.867 F -p(=o)(ocH2-cF3)2 IAa.868 F -p(=o)(ocH2-cH2-oH~2 IAa.869 F -P(=O)(OCH2-CH2-CN~2 IAa.870 F -p(=o)(ocH2-cH2-ocH3)2 IAa.871 F -p(=o)(ocH2-cH2-oc2Hs)2 IAa.872 F -p(=o)(ocH2-cH2-ocF3)2 IAa.873 F -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 IAa.874 F -P(=O)(OCH2-CH2-OCH2-C= CH)2 IAa.875 F -P(=O)(OCH2-CH2-O-cyclopentyl~2 IAa.876 F -P(=O)(OCH2-CHz-NH2)2 IAa.877 F -P(=O)(OCH2-CH2-NH-CH3)2 IAa.878 F -P(=O)[OCH2-CH2-N(CH3)2~2 IAa.879 F -p(=o)(ocH2-cH2-scH3)2 IAa.880 F -P(=O)(OCH2-CH2-SC2Hs)2 IAa.881 F -p(=o)(ocH2-cH2-scF3)2 IAa.882 F --P(=O)(OCEl2-CH2-SCH2-CH=cH2)2 IAa.883 F -P(=O)(OCE32-CH2-SC~2--C2 CH)2 IAa.884 F --P(=O)(OCH2-CH2-SO-cHB)2 IAa.885 F -p(=o)(ocH2-cH2-so-c2Hs)2 0050/46586 CA 02245659 l998-08-06 No. R4 _p(=yl)(Y2R1)(Y3R2) IAa.886 F -p(=o)(ocH2-so2-cH3)2 LAa.887 F -p(=o)(ocH2-so2-c2Hs)2 5IAa.888 F -p(=o)(ocH2-cH2-so2-cH3)2 L~a.889 F -p(=o)(ocH2-cH2-so2-c2Hs)2 IAa.890 F -p(=o)(ocH2-cH=cH2)2 IAa.891 F -p(=o)(ocH2-cH=cH-cH3)2 L~a.892 F -p(=o)(ocH2-cH2-cH=cH2)2 IAa.893 F -P(=O)(OCH2-CH=CH-Cl~2 L~a.894 F -p(=o)(ocH2-c--CH)2 IAa.895 F -P(=O)[OCH(CH3)-C--CH]2 IAa.896 F -p(=o)(ocH2-co-ocH3)2 15IAa.897 F _p(=o)(ocH2-co-oc2Hs)2 a.898 F -P(=O)[OcH(cH3)-cO-OcH3]2 IAa.899 F -P(=O)[OCH(CH3)-CO-OC2Hs]2 IAa.900 F -p(=o)(ocH2-co-N~2)2 20L~a.901 F -p(=o)(ocH2-co-NH-cH3)2 IAa.902 F -P(=O) OcH2-co-N(cH3)2]2 IAa.903 F -P(=O) OCH(CH3)-CO-N~2]2 IAa.904 F -P(=O)-OCH(CH3)-CO-NH-CH3]2 25IAa.905 F -P(=O) OCH(CH3)-CO-N(CH3)2]2 IAa.906 F -P(=O)(O-cyclopropyl~
L9a.907 F -P(=O)(O-cyclobutyl~Q
IAa.908 F -P(=O)(O-~;y~lOp~lllyl~2 IAa.909 F --P(=O)(O--cyclohe~cyl~2 IAa.910 F -P(=O)(OCH2-cyclopropyl)2 a.911 F -P(=O)(OCE~2-cyclobutyl)2 IAa.912 F -P(=O)(OCH2-cyclopent-yl)2 IAa.913 F -P(=O)(OCH2-cyclohexylh 35 IAa.914 F -P(=O)(O-phenyl~
IAa.915 F -P(=O)(OCH2-phenylh IAa.916 F -P(=O)(O-oxetan-3-yl~
IAa.917 F -P(=O)(O-tetrahydlorul~-2-yl~
40 IAa.918 F -P(=O)(O-tetrahydrofuran-3-yl~
IAa.919 F --P(=O)(O-tetraLydlo~,ylan-2--yl~
IAa.920 F -P(=O)(O-tetrahy&o~yld.~-3--yl~
IAa.921 F --P(=O)(O-tetrallydlol,ylail-4 IAa.922 F -P(=O)(OCHz-oxiran-2-yl~2 -IAa.923 F -P(=O)(OCH2-oxetan-3-ylk IAa.924 F -P(=O)(OCH2-tetrahydlorulan-2-yl~
.
54 _.
No. R4 --p(=y1)(Y2R1)(Y3R2) IAa.925 F -P(=O)(OCH2-tetrally&oru,an-3-yl~
IAa.926 F -P(=O)(OCH2-pyrrolidin-l-yl~
IAa.927 F -P(=O)[OCH2-(2-pyrrolidon-1-yl)~
IAa.928 F -P(=O)(OCHz-tetral y~l~o~y~-2-yl~
IAa.929 F -P(=O)(OCH2-tetrahy&~ylan--3-yl~
LAa.930 F -P(=O)(OCH2-tetrahy dl c~y ~ an-4-yl~
IAa.931 F -p(=o)(ocH2-riren~lin-l-yl~?
IAa.932 F -P(=O)(OCH2-morpholin-4-yl~
IAa.933 F -P(=O)(OH)(OCH3) L~a.934 F -p(=o)(oH)(oc2Hs) IAa.935 F -P(=O)(OH) O-[n-C3H7)]
LAa.936 F -P(=O)(OH) OCH(CH3)2]
IAa.937 F -P(=O)(OH) O-(n-CiHg)]
IAa.938 F -P(=O)(OH) OcH2-cH(cH3)2 IAa.939 F -P(=O)(OH) ocH(cH3)-c2Hs IAa.940 F -P(=O)(OH)(OCH2-CF3) IAa.941 F -P(=O)(OH)(OCH2-CH2-OH) IAa.942 F -P(=O)(OH)(OCH2-CH2-CN) IAa.943 F -P(=O)(OH)(OCH2-CH2-OCH3) IAa.944 F -p(=o)(oH)(ocH2-cH2-oc2Hs) IAa.945 F -P(=O)(OH)(OCH2-CH2-OCF3) IAa.946 F -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) IAa.947 F -P(=O)(OH)(OCH2-CH2-OCH2-C--CH) IAa.948 F -P(=O)(OH)(OCH2-CH2-O-cyclopentyl) IAa.949 F -P(=O)(OH)(OCH2-CH2-NH2) IAa.950 F -P(=O)(OH)(OCH2-CH2-NH-CH3) -_ IAa.951 F -P(=O)(OH)tOCH2-CH2-N(CH3)2]
IAa.952 F -P(=O)(OH)(OCH2-CH2-SCH3) 3 5 IAa.953 F --P(=O)(OH)(OCH2-CH2-Sc2Hs) IAa.954 F -P(=O)(OH)(OCH2-CH2-SCF3) IAa.9SS F -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.956 F -P(=O)(OH)(OCH2-CH2-SCH2-C----CH) IAa 957 F -P(=O)(OH)(OCH2--CH2-SO--CH3) IAa.958 F -P(=O)(OH)(OCH2-CH2-SO-C2H~) IAa.9S9 F --P(=O)(OH)(OCH2-SO2-CH3) IAa.960 F -p(=o)(oH)(ocH2-so2-c2Hs) IAa.961 F -P(=O)(OH)(OCH2--CH2--SO2--CH3) IAa.962 F -P(=O)(OH)(OCH2-CH2-SO2-C2Hs) IAa.963 F -p(=o)(oH)(ocH2-cH=cH2) OOSO/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)(y2Rl)(y3R2) IAa.964 F -P(=O)(OH)(OCH2-CH=CH-C~) IAa.965 F -p(=o)(oH)(ocH2-cH2-cH=cH2) 5 IAa.966 F -P(=O)(OH)(OCH2-CH=CH-Cl) IAa.967 F -P(=O)(OH)(OCH2-C= C~I) IAa.968 F -P(=O)(OH)[OCH(CH3)-C--CH
IAa.969 F -P(=O)(OH)(OCH2-CO-OCH3) IAa.970 F -P(=O)(OH)(OCH2-CO-OC2Hs) IAa.971 F -P(=O)(OH) OCH(CH3)-CO-OCH3]
IAa.972 F -P(=O)(OH) OCH(CH3)-CO-OC2H5]
IAa.973 F -P(=O)(OH)(OCH2-CO-NEI2) IAa.974 F -P(=O)(OH)(OCH2-CO-NH-CEO
15 IAa.975 F -P(=O)(OH)[OcH2-cO-N(c~3)2]
-- IAa.976 F -p(=o)(oH)[ocH(cH3)-co-NEI2]
IAa.977 F -P(=O)(OH)[OCH(CH3)-CO-NH-C~]
IAa.978 F -P(=O)(OH)[OCH(CH3)-CO-N(C~3)2]
20 IAa.979 F -P(=O)(OH)(O-cyclopropyl) IAa.980 F -P(=O)(OH)(O-cyclobutyl) IAa.981 F -P(=O)(OH)(O-cyclopentyl) IAa.982 F -p(=o)(oH)(o-cyclohe~cyl) 25 IAa.983 F -P(=O)(OH)(OCH2-cyclopropyl) IAa.984 F -P(=O)(OH)(OCH2-cyclobutyl) IAa.985 F -P(=O)(OH)(OCH2-cycloye ~ ~ Iyl) IAa.986 F -P(=O)(OH)(OCH2-cyclohexyl) IAa.987 F -P(=O)(OH)(O--phenyl) IAa.988 F -P(=O)(OH)(OCH2-phenyl) ~,IAa.989 F --P(=O)(OH)(O-o~etan--3--yl) -IAa.990 F -P(=O)(OH)(O-tetrahy~Lvr~lla~.-2-yl) IAa.991 F -P(=O)(OH)(O-tetrahyd-orulall-3-yl) 35 IAa.992 F -P(=O)(OH)(O-tetrahyLo~y~all-2-yl) IAa.993 F -P(=O)(OH)(O--tetraLy~Ilol,ylall-3-yl) IAa.994 F -P(=O)(OH)(O-tetrahy~Lo~ylan-4-yl) IAa.995 F -P(=O)(OH)(OCH2-oxiran-2-yl) 40 IAa~996 F -P(=O)(OH)(OCH2-o~etan-3-yl) IAa.997 F -P(=O)(OH)(OCH2-tetral~ydlorulau--2--yl) IAa.998 F -P(=O)(OH)(OCH2-tetral-ydlc,Lulail-3-yl) IAa.999 F -P(=O)(OH)(OCH2-pyrrolidin-1-yl) 45 IAa.1000 F -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
IAa.1001 F --P(=O)(OH)(OCH2--tetrallydl~ylan--2--yl) IAa.1002 F -P(=O)(OH)(OCH2-tetral.ydlo~,ylan-3-yl) 0050/46586 CA 0224~6~9 19s8-08-06 .
56 _ No. R4 -P(=yl)~y2Rl)~y3R2) IAa.1003 F -P(=O)(OH)(OCH2-tetra~y~o~.an-4-yl) IAa.1004 F -P(=O)(OH9(0CH2-pipendin-1-yl) 5 IAa.lOU5 F -P(=O)(OH)(OCH2-morpholin-4-yl) IAa.1006 F -P(=O)(OCH3)(OC2Hs) IAa.1007 F -P(=O)(OCH3)[O-(n-C3H7)]
L~a.1008 F -P(=O)(OCH3)[0CH(CH3)2]
IAa.1009 F - P(=O)(OCH3) O-(n-C~Hg)]
~Aa.1010 F --P(=O)(OCH3) 0CH2-CH(CH3)2]
IAa.1011 F -P(=O)(OCH3) OCH(CH3)-C2Hs]
IAa.1012 F -P(=O)(OCH3)(OCH2-CF3) IAa.1013 F -P(=O)(OCH3)(OCH2-CH2-OH) 15 IAa.lO14 F -P(=O)(OCH3)(0CH2-CH2-CN~
~IAa.1015 F -P(=O)(OCH3)(OCH2-CH2-OCH3) ~-IAa.1016 F -P(=O)(OCH3)(OCH2-CH2-OC2Hs) IAa.1017 F -P(=O)(OCH3)(OCH2-CH2-OCF3) 20 LAa.1018 F -P(=O)(OCH3)(OCH2-CH2-OCH2-CH=CH2) IAa.1019 F -P(=O)(OCH3)(OCH2-CH2-OCH2-C-- CH) IAa.1020 F -P(=O)(OCH3)(OCH2-CH2-O-cyclopentyl) IAa.1021 F -P(=O)(OCH3)(0CH2-CH2-NH2) 25 IAa.1022 F -P(=O)(OCH3)(OCH2-CH2-NH-CH3) IAa.1023 F -P(=O)(OCH3)[0CH2-CH2-N(CH3)2]
IAa.1024 F -P(=O)(OCH3)(OCH2-CH2-SCH3) IAa.1025 F -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.1026 F -P(=O)(OCH3)(OCH2-CH2-SCF3) ~ IAa.1027 F -P(=O)(OCH3)(0CH2-CH2-SCH2-CH=CH2) IAa.1028 F -P(=O)(OCH3)(0CH2-CH~-SCH2--C--CH) LAa.1029 F -P(=O)(OCH3)(0CH2-CH2-SO-CH3) IAa.1030 F -P(=O)(OCH3)(OCH2-CH2-SO-C2Hs) 35 IAa.1031 F -P(=O)(OCH3)(OCH2-SO2-CH3) IAa.1032 F -P(=O)(OCH3)(OCH2-SO2-C2Hs) IAa.1033 F -P(=O)(OCH3)(OCH2-CH2-SO2-CH3) IAa.1034 F -P(=O)(OCH3)(OCH2-CH2-SO2-C2Hs) 40 IAa.1035 F -P(=O)(OCH3)(OCH2-CH=CH2) IAa.1036 F -P(=O)(OCH3)(OCH2-CH=CH-CH3) IAa.1037 F -P(=O)(OCH3)(OCH2-CH2-CH=CH2) IAa.1038 F -P(=O)(OCH3)(OCH2-CH=CH-Cl) IAa.1039 F -P(=O)(OCH3)(OCH2-C- CH) IAa.1040 F -P(=O)(OCH3)[0CH(CH3)-C_ CH~
IAa.1041 F -P(=O)(OCH3)(OCH2-CO-OCH3) 57 _ No. R4 _p(=yl)(y2Rl)(y3Rz) IAa.1042 F -P(=O)(OCH3)(OCH2-CO-OC2Hs) IAa.1043 F -P(=O)(OCH3) OCH(CH3)-CO-OCH3]
5 IAa.1044 F -P(=O)(OCH3) OCH(CH3)-CO-OC2Hs]
IAa.1045 F -p(=o)(ocH3)(ocH2-co-N~2) IAa.1046 F -P(=O)(OCH3)(OCH2-CO-NH-C~) IAa.1047 F -P(=O)(OCH3)[OCH2-CO-N(CH3)2]
IAa.1048 F -P(=O)(OCH3)[0CH(CH3)-CO-N~2]
IAa.1049 F -P(=O)(OCH3)[0CH(CH3)-CO-NH-C~;]
IAa.1050 F -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.1051 F -P(=O)(OCH3)(O-cyclopropyl) IAa.1052 F -P(=O)(OCH3)(0-cyclobutyl) lS IAa.1053 F -P(=O)(OCH3)(0-cyclopentyl) IAa.1054 F -P(=O)(OCH3)(O-cyclohexyl) IAa.1055 F -p(=o)(ocH3)(ocH2-~;yolo~o~yl) IAa.1056 F -P(=O)(OCH3)(0CH2-cyclobutyl) 20 IAa.1057 F -P(=O)(OCH3)(OCH2-cyclopentyl) IAa.1058 F -P(=O)(OCH3)(OCH2-cyclohexyl) IAa.1059 F -P(=O)(OCH3)(O-phenyl) IAa.106Q F -P(=O~(OCH~(OCH2-phenyl) 25 IAa.1061 F -P(=O)(OCH3)(0-oxetan-3-yl) IAa.1062 F -P(=O)(OCH3)(0-tetrally&~.rul~-2-yl) IAa.1063 F -P(=O)(OCH3)(O-tetrahy-l.orulc,n-3-yl) L~a.1064 F -P(=O)(OCH3)(O-tetrally&u~y,an-2-yl) IAa.1065 F -P(=O)(OCH3)(O-tetrahy~Lo~y.a.l-3-yl) IAa.1066 F -P(=O)(OCH3)(O-tetral,y-l.u~,y.dn-4-yl) IAa.1067 F -P(=O)(OCH3)(OCH2-oxiran-2-yl) f' IAa.1068 F -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.1069 F -P(=O)(OCH3)(OCH2-tetral~yd~uru~ -2-yl) 35 IAa.1070 F --P(=O)(OCH3)(0CH2-tetrahydrofuran-3-yl) IAa.1071 F -P(=O)(OCH3)(0CII~ ~y~ulidin-1-yl) IAa.1072 F -P(=O)(OCH3)tOCH2-(2-pyrrolidon-1-yl)]
IAa.1073 F -P(=O)(OCH3)(OCH2-tetrahy~llu~ylan-2-yl) 40 IAa.1074 F -P(=O)(OCH3)(OCH2-tetraLydlo~y~-3-yl) IAa.1075 F -P(=O)(OCH3)(OCH2-tetrahy-l.u~y.dn-4-yl) IAa.1076 F -P(=O)(OCH3)(OCH2-piperi(lin-1-yl) IAa.1077 F -P(=O)(OCH3)(OCH2-morpholin-4-yl) 45 IAa.1078 F --P(=O)(OC2Hs)[O-(n-C3H7)]
L~a.1079 F -p(=o)(oc2Hs)[ocH(cH3)2]
IAa.1080 F --P(=O)(OC2Hs)[O-(n-ciH9)]
0050/46586 CA 0224~6~9 1998-o8-b6 No. R4 _p(=yl)cy2Rl)cy3R2) I~a.1081 F --P(=O)(OC2Hs)[OCH2-CH(CH3)2]
LAa.1082 F -p(=o)(oc2H5)[ocH(cH3)-c2H5]
5LAa.1083 F -P(=O)(OC2H5)(0CH2-CF3) LAa.1084 F -P(=O)(OC2H5)(0CH2-CH2-OH) LAa.1085 F -P(=O)(OC2H5)(0CH2-CH2-CN) I~a.1086 F -P(=O)(OC2H5)(0CH2-CH2-OCH3) LAa.1087 F -P(=O)(OC2H5)(0CH2-CH2-OC2H5) I~a.1088 F -P(=O)(OC2H5)(0CH2-CH2-OCF3) LAa.1089 F -p(=o)(oc2H5)(ocH2-cH2-ocH2-cH=cH2) I~a.1090 F -P(=O)(OC2H5)(0CH2-CH2-OCH2-C3 CH) I~a.1091 F -P(=O)(OC2H5)(0CH2-CH2-O-cyclopentyl) 15LAa.1092 F -p(=o)(oc2H5)(ocH2-cH2-NH2) a.1093 F -P(=O)(OC2H5)(0CH2-CH2-NH-CH3) LAa.1094 F -p(=o)(oc2H5)[ocH2-cH2-N(cH3)2]
LAa.1095 F -P(=O)(OC2H5)(OCH2-CH2-SCH3) 20LAa.1096 F -P(=O)(OC2Hs)(OCH2-CH2-SC2H5) LAa.1097 F -P(=O)(OC2H5)(0CH2-CH2-SCF3) LAa.1098 F -P(=O)(OC2Hs)(OCH2-CH2-SCH2-CH=CH2) LAa.1099 F -P(=O)(OC2H5)(0CH2-CH2-SCH2-C2 CH) 25LAa.llO0 F -P(=O)(OC2H5)(0CH2-CH2-SO-CH3) LAa.llOl F -P(=O)(OC2H5)(0CH2-CH2-SO-C2H5) LAa.1102 F --P(=O)(OC2H5)(OCH2-SOz-CH3) LAa.1103 F --P(=O)(OC2H5)(0CH2--S02--C2H5) LAa.1104 F -P(=O)(OC2H5)(0CH2-CH2-SO2-CH3) I~a.1105 F -P(=O)(OC2H5)(0CH2-CH2-SO2-C2H5) a.1106 F --P(=O)(OC2H5)(0CH2-CH=CH2) LAa.1107 F -P(=O)(OC2H5)(0CH2-CH=CH-CH3) LAa.1108 F -p(=o)(oc2H5)(ocH2-cH2-cH=cH2) 35I~a.llO9 F -P(=O)(OC2H5)(0CH2-CH=CH-Cl) LAa.lllO F -P(=O)(OC2H5)(0CH2-C2 CH) I~a.llll F --P(=O)(OC2H5)[OCH(CH3)--C--CH]
I~a.1112 F -P(=O)(OC2Hs)(OCH2-CO-OCH3) 40LAa.1113 F -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~.1114 F - P(=O)(OC2H5)[OCH(CH3) - CO - OCH3]
a.1115 F -P(=O)(OC2H5)[0CH(CH3)-CO-OC2H5]
I~.1116 F -P(=O)(OC2H5)(OCH2-CO-N~2) 45I~.1117 F -P(=O)(OC2H5)(OCH2-CO-NH-CH~) I~a.1118 F -p(=o)(oc2H5)[ocH2-co-N(cH3)2]
LAa.lll9 F -p(=o)(oc2H5)[ocH(cH3)-co-NH2]
0050/46586 CA 0224~6~9 l998-08-06 .
.
59 . _ No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1120 F ~P(=o)(oc2Hs)[ocH(cH3)-co-NH
IAa.1121 F -P(=O)(OC2Hs)[ocH(cH3)-co-N(cH3)2 5 IAa.1122 F -P(=O)(OC2Hs)(O-cyclopropyl) IAa.1123 F -P(=O)(OC2Hs)(O-cyclobutyl) IAa.1124 F -P(=O)(OC2Hs)(O-cydopentyl) IAa.1125 F -P(=O)(OC2Hs)(O-cy-clohe~yl) IAa.1126 F -P(=O)(OC2Hs)(OCH2-cyclopropyl) IAa.1127 F -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.1128 F -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa.1129 F --P(=O)(OC2Hs)(OCH2-cyclohexyl) IAa.1130 F _p(=o)(oC2Hs)(O-PhenYl) 15 IAa~ll3l F ~P(=o)(oc2Hs)(ocH2-phenyl) -IAa.1132 F -P(=O)(OC2Hs)(O-oxetan-3-yl) IAa.1133 F --P(=~)(~C2Hs)(O-tetral y& uru. an-2-yl) IAa.1134 F ~p(=o)(oc2Hs)(o-tetrahy&~lfuldll-3-yl) 20 IAa.1135 F ~P(=~)(~C2Hs)(O-tetrahydlo~,y.an-2-yl) IAa.1136 F ~p(=o)(oc2Hs)(o-tetrahyd~o~y~an-3-yl) IAa.1137 F ~P(=~)(~C2Hs)(O-tetrahydlo~,y~all~-yl) IAa.1138 F -P(=O)(OC2Hs)(OCH2-oxiran-2-yl) 25 IAa.1139 F -P(=O)(OC2Hs)(OCH2-o~etan-3-yl) IAa.1140 F --P(=O)(OC2Hs)(OCH2-tetrahydrofuran-2-yl) IAa.1141 F -P(=O)(OC2Hs)(OCH2-tet~ahy~l.oru.a~l-3-yl) IAa.1142 F --P(=O)(OC2Hs)(OCH2-pyrrolidin-l--yl) IAa.1143 F -P(=O)(OC2Hs)[OCH2-(2-pyrrolidon-l-yl)]
LAa.1144 F -P(=O)(OC2Hs)(OCH2-tetrahyd.. ,~ylail-2-yl) __ IAa.1145 F -P(=O)(OC2Hs)(OCH2-tetrahydlopy.àil-3-yl) IAa.1146 F -P(=O)(OC2Hs)(OCH2-tetrahyd.o~ylan-4-yl) IAa.1147 F --P(=O)(OC2Hs)(OCH2--pip~ori(1in--l--yl) IAa.1148 F -P(=O)(OC2Hs)(OCH2-morpholin-4-yl) IAa.1149 F --P(=0)(1,2--phenylenf~iioxy) IAa.1150 F -P(=O)(O-CEI2-CH2-O) IAa.llSl F -P(=O) O-CH(CH3)-CH2-O]
40 IAa.llS2 F -P(=O) Q-CH(CH3)-CH(CH3)-O]
IAa.1153 F -P(=O) O-CH(COOCH3)-CH(COOCH3)-O]
IAa.1154 F _P(=o)(o-c~2-cH2-cH2-o) IAa.llSS F -P(=O)[O-CE~2-C(CH3)2-CH2-O]
45 IAa.1156 F -P(=O)(O-C~2-CH2-CH2-CH2-O) - IAa.1157 F -P(=S)(OH~2 IAa.1158 F -P(=S)(OCH3)2 0050/46586 CA 02245659 l998-08-06 No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1159 F -p(=s)(oc2Hs)2 IAa.1160 F -P(=S) o-(n-c3H7)]2 5 IAa.1161 F -P(=S) o-(n-clHs)]2 IAa.1162 F -p(=s)(o-c~2-cH2-cH2-o) IAa.1163 F -P(=O)(NH2)2 IAa.1164 F -P(=O)(NH-CH~)2 IAa.1165 F -P(=O)tN(CH3)2]2 IAa.1166 F -p(=o)(NH-c2Hs)2 IAa.1167 F -P(=O)[N(C2Hs)2]2 IAa.1168 F -p(=o)(NH-cH2-cH=cH2)2 IAa.1169 F -P(=O)(NH-CE~2-C--CH)2 15 IAa.1170 F -P(=O)~H-~iydo~lu,uYl~e fIAa.1171 F -P(=O)(NH-CEI2-cyclopentyl~2 IAa.1172 F -P(=O)(NH-phenyl~z IAa.1173 F -p(=o)(NH-cH2-phenyl~2 - 20 IAa.1174 F -P(=O)(pyrrolidin-1-yl~
IAa.1175 F -P(=0)(2-methoxycarbc,~yl~y,.~,lidin-1-yl~
IAa.1176 F -P(=O)(NH-CH2-CO-OCH3)2 IAa.1177 F -P(=O)[N(CH3)-CH2-CO-OC~3]2 25 IAa.1178 F -P(=O)(NH-CE~2-CO-OC2Hs)2 IAa.1179 F -p(=o)[N(cH3)-cH2-co-oc2Hs]2 IAa.1180 F -P(=O)tNH-CH(CH3)-cO-Oc~3]2 IAa.1181 F --P(=O)(OH)(NH2) IAa.1182 F -P(=O)(OH)(NH-CHB) IAa.1183 F -P(=O)(OH)[N(CH3)2]
IAa.1184 F -P(=O)(OH)(NH-C2H5) _ IAa.1185 F -P(=O)(OH)tN(C2Hs)2]
IAa.1186 F -P(=O)(OH)(NH-CH2-CH=CH2) 35 IAa.1187 F -P(=O)(OH)(NH-CK2-C--CH) IAa.1188 F -P(=O)(OH)(NH-cyclopropyl) IAa.1189 F -P(=O)(OH)(NH-CH2-cydopentyl) IAa.1190 F -P(=O)(OH)(NH-phenyl) 40 IAa.l191 F -P(=O)(OH)(NH-CH2-phenyl) IAa.1192 F --P(=O)(OH)(pyrrolidin--1-yl) IAa.1193 F -P(=O)(OH)(2-methu~y~bol-yl~y.. (Jlidin-1-yl) IAa.1194 F -p(=o)(oH)(NH-cH2-co-ocH3) IAa.1195 F -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
IAa.1196 F -P(=O)(OH)(NH-CK2-CO-OC2Hs) IAa.1197 F -P(=O)(OH)[N(CH3)-CH2-CO-OC2Hs]
0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=y1)(y2Rl)(y3R2) IAa.1198 F -P(=O)(O~[NH-CH(CH3)-CO-OCH3]
IAa.1199 F -P(=O)(OCH3)(NH2) IAa.1200 F -P(=O)(OCH3)(NH-CH3) IAa.1201 F -P(=O)(OCH3)[N(CH3)2~
IAa.1202 F -P(=O)(OCH3)(NH--C2Hs) IAa.1203 F -P(=O)(OCH3)[N(C2Hs)2]
IAa.1204 F -P(=O)(OCH3)(NH-CH2-CH=CH2) IAa.1205 F -P(=O)(OCH3)(NH-CH2-C--CH) IAa.1206 F -P(=O)(OCH3)(NH-cydopropyl) IAa.1207 F -P(=O)(OCH3)(NH-CH2-cyclopentyl) IAa.1208 F -P(=O)(OCH3)(NH-phenyl) IAa.1209 F -P(=O)(OCH3)(NH-CH2-phenyl) - IAa.1210 F -P(=O)(OCH3)(pyrrolidin-1-yl) ~-IAa.1211 F -P(=O)(OCH3)(2-metho~y~-ln,--yl~y.. olidin-1-yl) IAa.1212 F -P(=O)(OCH3)~NH-CH2-CO-OCH3) IAa.1213 F -p(=o)(ocH3)[N(cH3)-cH2-co-ocH3]
IAa.1214 F -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.1215 F -P(=O)(OCH3)[N(CH3)-CH2-CO-OC2Hs]
IAa.1216 F -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
IAa.1217 F -p(=o)(oc2Hs)(NH2) IAa.1218 F -P(=O)(OC2Hs)(NH--CH3) IAa.1219 F -p(=o)(oc2Hs)[N(cH3)2]
IAa.1220 F -P(=O)(OC2Hs)(NH-C2HS) IAa.1221 F -p(=o)(oc2Hs)tN(c2Hs)2]
IAa.1222 F -p(=o)(oc2Hs)(NH-cH2-cH=cH2) IAa.1223 F -P(=o)(oc2Hs)(NH-cH2-c--CH) LAa.1224 F -P(=O)(OC2Hs)(NH-cyclopropyl) IAa.1225 F -P(=O)(OC2Hs)(NH-CH2-cyclopentyl) IAa.1226 F -P(=O)(OC2Hs)(NH-phenyl) IAa.1227 F -P(=O)(OC2Hs)(NH--CH2--phenyl) IAa.1228 F -P(=O)(OC2Hs)(pyrrolidin-1-yl) IAa.1229 F -P(=O)(OC2Hs)(2-metho~y~all~G.. yl~Jyl.olidin-1-yl) IAa.1230 F -P(=O)(OC2Hs)(NH-CH2-CO-OCH3) IAa.1231 F -P(=O)(OC2Hs)[N(CH3)--CH2-CO-OCE~3]
L~a.1232 F -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.1233 F -P(=O)(OC2HS) N(CH3)-CH2-CO-OC2Hs]
IAa.1234 F -P(=O)(OC2Hs) NH-CH(CH3)-CO-OCH3]
IAa.1235 F -P(=O) N(CH3)2 (OCH3) IAa.1236 F -P(=O)rN(CH3)z (OC2Hs) ~ 0050/46586 CA 02245659 l998-08-06 ~ .
No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1237 F ~P(=o)tN(cH3)2][o-(n-c3H7)]
LAa.1238 F -p(=o)tN(cH3)2] OCH(CH3)2]
5 IAa.l239 F -P(=o)[N(cH3)2l O-(n-C1Hs)]
IAa.1240 F -p(=o)tN(cH3)2(oCH2-cH=cH2) IAa.1241 F -P(=O)tN(CH3)2(OCH2-C-- CH~
IAa.1242 F -P(=O) N(CH3)2](O-cyclohe~yl) IAa.1243 F -P(=O) N(CH3)2](OCH2-cyclohe~yl) 1IAa.1244 F -P(=O) N(CH3)2](O-phenyl) IAa.1245 F -P(=o)[N(cH3)2](ocH2-phenyl) IAa.1246 F -P(=O) N(CH3)2(0-tetra~y~vru~o~-2-yl) IAa.1247 F -P(=O) N(CH3)i(OCH2-oxetan-3-yl) 15 IAa.l248 F -P(=O)-N(CH3)2(OCH2-CF3) -IAa.1249 F -P(=O)tN(CH3)2(OCH2-CO-OC~3) ~~~ IAa.1250 F -P(=O)[N(CH3)2(OCH2-CO-OC2Hs) IAa.1251 F -P(=O)~NH-C~2-CH2-O) 20 IAa.1252 F -P(=O)~NH-CH2-CH2-NH~
IAa.1253 F -P(=O)tN(CH3)-CH2-CH2-N(CH3)]
IAa.1254 F -p(=o)(NH-cH2-cH2-cH2-o) IAa.1255 F -P(=O)~NH-CH2-CH2-CH2-NH9 25 IAa.1256 F -P(=O)tN(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.1257 F -p(=o)(o-cH2-cH(cH3)-cH2-o) IAa.1258 F -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.1259 F -P(=O)tN(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.1260 F -P(=O) NH-CH2-CH2-CH2-CH2-O]
lAa.1261 F -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.1262 F -P(=S)~NH2)2 IAa.1263 F -P(=S)(NH-CH3)2 IAa.1264 F -P(=S)tN(CH3)2]2 35 IAa.1265 F -P(=S)(NH-C2H5)2 IAa.1266 F -P(=S)[N(C2H5)2]2 IAa.1267 F -P(=S)~NH-CH2-CH2-CH2-O) IAa.1268 F -P(=S)~NH-CH2-CH2-CH2-NH~
40 IAa.l269 F -P(--S)[N(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.1270 F -P(=O)(SCH3)2 IAa.1271 F -p(=o)(sc2Hs)2 IAa.1272 F -P(=O)S-(n-C3H7)2 45 IAa.1273 F -P(=O) SCH(CH3)2 2 IAa.1274 F -p(=o)s-(n-~H9)l2 IAa.1275 F -p(=o)(scH2-cH=cH2)2 OOSO/46586 CA 02245659 l998-08-06 ~, . . . .
No. R4 -P(=yl)cyzRl)cy3R2) I~.1276 F -P(=O)(S-phenyl~
L~a.1277 F -P(=O)(SC~H2-phenyl~
5 LAa.1278 F -p(=o)(sc~H2-co-oc~)2 I~.1279 F -P(=O)(SC~H2-CO-OC2Hs)2 LAa.1280 F -P(=O)(S-C~H~-C~H~-C~H2-S) LA~.1281 F -P(=o)(s-c~H~ H2-c~H2-o) I~.1282 F -P(=S)(SC~H3)2 LAa.1283 F -P(=S)(SC2Hs)2 IAa.1284 F -p(=s)[s-(n-c~H7)]2 LAa.1285 ~ -P(=S)~S-n-CiHs)]2 LA a.1286 P -P(=S)(S--C~H~--C~H2-C~H2-S) LAa.1287 F -P(=S)(S-C~H~-C~H2-C~2-O) Further especially preferred aromatic phosphonic acid derivatives are those of the form~ e IAb-IAn, IBa-IBn, ICa-ICn, IDa-IDn, 20 IEa-IEn, IFa-IFn, IGa-IGn, IHa-IHn, IKa-IKn, ILa-ILn, IMa-IMn and INa-INn, in particular - the compounds IAb~l - IAb.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is 25 --CH2--CH(Cl)--:
~ N
~ ~cO
~ N Cl ~-1 IAb (~ R ~ CH2 - CH ~ _ y Cl y3R2 - the compounds IAc.l - IAc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)-:
~-N
~/ )=O
~ N Br --1 IAc R4 ~ CH2 CH ~ - Y2R
Cl y3R2 ~ ~ 64 - the compounds IAd.1 - IAd.1287~ which differ from the corres-ponding c~ _unds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CN)-:
~ N
~ )=o 10~ ~ CN -l IAd Cl y3R2 - the c~~ ,~unds IAe.1 - IAe.1287, which differ from the corres-;~ ponding compounds IAa.1 - IAa.1287 only in that Eth is -cH2-cH(c~3)-:
~ ~~
25R4 ~ CH2 C~ y2Rl IAe C 1 y3R2 30 - the compounds IAf.1 - IAf.1287, which differ from the corres-ponding c~...~o~nds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)-:
~ N OCH3 ~_ ~~
//~ CH2 CH--~--y2Rl IAf ~
Cl y3R2 - the compounds IAg.1 - IAg.1287~ which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethenediyl:
0050/46586 CA 02245659 l998-08-06 ~ . . . .
_ N
~/ )cO
~N yl IAg R4~CH--CH . --Y2R
Cl y3R2 - the compounds IAh.1 - IAh.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C ( Cl )--:
C ' ~ ~= o ZO ~ ~3 C~ = C--'--Y~R
Cl y3R2 - the col.l~ounds IAi.1 - IAi.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Br)-:
f~ ~N
~N Br ~,1 IAi ~ ~ CH - l ~ Y2Rl Cl y3R2 40 - the compounds IAj.1 - IAj.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)-:
~N
k ~ CN .rl IAj R~.... ~CH = C ~ y2Rl Cl y3R2 - the compounds IAk.1 - IAk.1287, which differ from the corres-ponding co~uunds IAa.1 - IAa.1287 only in that Eth is 15 --CH=C (CH3 )--:
,.~ . F3C ~CH3 ~ N
R4~CEI= C --~--Y~Rl IAk C 1 y3R2 - the compounds IAm.1 - IAm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C ( COOCH3 )--:
,~ N OCH3 ~,' ~ ~0 ~ ~ CO yl IAm R4~CH C--. '_y2Rl Cl y3R2 40 - the compounds IAn.1 - IAn.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -C-C-:
0050/46586 CA 0224~659 1998-08-06 N
~ IAn R4 ~ C _ C - ~ _ y2Rl Cl y3R2 - the co-l~ounds IBa.430 - IBa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where R10 = methyl, Rl1 = difluoromethoxy and R12 - chlorine:
F2HCO Cl =~ vl ~N~ ~ IBa H3C N ~ CH2 - CH2- ' y Cl y3R2 25 - the compounds IBb.430 - IBb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)-- and R5 is the heterocycle '~I>2 where Rl~ = methyl, R11 c difluoromethoxy and Rl2 = chlorine:
F2HCO Cl C ~ C~z - C~ - I - Y2RI IBb Cl y3R2 - the compounds IBc.430 - IBc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2--CH(Br)--and R5 is the heterocycle ~2 where R10 = methyl, Rll ~ difluoromethoxy and Rl2 = chlorine:
~ , .
F2HCO Cl ~ Br yl H3C ~CH2 - CH y2Rl IBc Cl y3R2 lO - the compounds IBd.430 - IBd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where R10 = methyl, Rl1 2 difluoromethoxy and R12 = chlorine:
F2HCO ~ Cl CN yl H3C~ 'N~CH2 CH--~--y2Rl IBd Cl y3R2 - the compounds IBe.430 - IBe.1287, which differ from the corres-ponding ~,--~vunds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~2 where R10 - methyl, Rll 5 difluoromethoxy and R12 = chlorine:
F2HCO Cl --~ CH3 yl 30H3C ~ 'N~ l ll IBe R4 ~ CH2 CH P y2 -- Cl y3R2 - the compounds IBf.430 - IBf.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is - CH2 - CH ( COOCH3 ) - and R5 is the heterocycle ~2 where Rlo =
methyl, R1l = difluoromethoxy and Rl2 = chlorine:
F2HCO ~ Cl ¦ .
-N ~ CH2 C~ _ y2Rl IBf Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 69 _ - the compounds IBg.430 - IBg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~2 where R10 = methyl, R1l = difluoromethoxy and Rl2 = chlorine:
F2HCO ~ Cl ,I yl H3C ~ 'N ~ ll IBg - R4 ~ CH - CH P - Y2Rl Cl y3R2 - the compounds IBh.430 - IBh.1287, which differ from the corres-15 ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, '~ Rll = difluoromethoxy and Rl2 = chlorine:
F2HCO Cl H3C ~ - CH - C - ~ - y2Rl IBh Cl y3R2 - the compounds IBi.430 - IBi.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~2 where R10 = methyl, Rll = difluoromethoxy and Rl2 = chlorine:
F2HCO Cl f ~ Br --1 H3C N ~ CH C y2Rl IBi C 1 y3R2 40 - the compounds IBj.430 - IBj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~2 where R10 = methyl, Rll - difluoromethoxy and Rl2 = chlorine:
~, . .
F2HCO Cl CN yl ~N~N ~ CH - C P y2Rl IBj Cl y3R2 lO - the compounds IBk.430 - IBk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~2 where Rl~ = methyl, Rll s difluoromethoxy and Rl2 = chlorine:
F2HCO Cl ~ CH3 yl ,N~N' ~ CH - C - P- Y2Rl IBk Cl y3R2 ZO
- the compounds IBm.430 - IBm.1287, which differ from the corres-po~ing compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~2 where R10 ~ methyl, Rll = difluoromethoxy and Rl2 - chlorine:
FzHCO Cl ~ CO -~1 H C ~N'N ~ CH 1 P y2Rl IBm Cl y3R2 - the compounds IBn.430 - IBn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C_C-and R5 is the heterocycle ~2 where Rlo = methyl, R11 = difluoro-methoxy and Rl2 = chlorine:
~ yl ~N~N' ~ - C _ C P Y2Rl IBn Cl y3R2 0050/46586 CA 0224~6~9 l998-08-06 .
- the compounds ICa.430 - ICa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 8 chlorine:
F3C Cl ~3C ~ CH2 - C~- ~ - Y2R~ ICa Cl y3R2 - the compounds ICb.430 - ICb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, i Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl ~ Cl ~1 ~N N ~ CH2 CH - ~ - y2Rl ICb Cl y3R2 - the compounds ICc.430 - ICc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~2 where Rl~ = methyl, 30 Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl Br ~-1 ~N~N ~ CH2 CH _ y2Rl ICc \=~ ' .
Cl y3R2 40 - the compounds ICd.430 - ICd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where RlO = methyl, Rll - trifluoromethyl and Rl2 = chlorine:
CA 0224~659 1998-08-06 F3C Cl . CN yl N~N ~ CH2 CH " y2Rl ICd Cl y3R2 10 - the compounds ICe.430 - ICe.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2--CH(CH3)-- and R5 is the heterocycle ~p2 where Rl~ = methyl, Rll = trifluoromethyl and R12 2 chlorine:
15 F3C Cl CH3 yl H3C ~ ~ ~ CH2 CH P y2Rl ICe Cl y3R2 - the compounds ICf.430 - ICf.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ,~p2 where R10 =
methyl, Rll - trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl H3C'' N ~ CO yl ICf R4 ~ / \ ~ CH2--CH--P y2 ~~ ~
Cl y3R2 - the compounds ICg.430 - ICg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2--ethenediyland R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluol~ -Lhyl and Rl2 8 chlorine:
~ . .
~ 73 F3C Cl ~3,3C~ C~=C~ - P - Y~RI ICg Cl y3R2 10 - the compounds ICh430 - ICh1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is --CH=C(Cl)--and R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl Cl yl H3C N ~ CH = C P _ y2Rl ICh Cl y3R2 - the compounds ICi.430 - ICi.287, which differ from the corres-ponding c~ ounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle ~2 where Rlo = methyl, Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl ~ Br yl ,N~N' ~ CH - C - P y2Rl ICi t ~ Cl y3R2 - the compounds ICj.430 - ICj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ~>2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl CN yl , N~N~ ~ CH = C --y2Rl ICj Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 .
74 _ - the compounds ICk.430 - ICk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C Cl CH3 yl N~N~CH C P- y2Rl ICk Cl y3R2 - the compounds ICm.430 - ICm.1287, which differ from the corres-ponding c~ unds IAa.430 - IAa.1287 only in that Eth is -CH=C (COOCH3 ) - and R5 is the heterocycle ~2 where R10 = methyl, ' Rll = trifluoromethyl and Rl2 - chlorine:
F3C =~ Cl CO yl ~N~N ~ CH = C - ~ y2Rl ICm Cl y3R2 - the compounds ICn.430 - ICn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~2 where R10 = methyl, R
trifluoromethyl and Rl2 3 chlorine:
.~. F3C --1=~ Cl H C ~N~N ~ ~ C = C - P _ y2Rl ICn Cl y3R2 40 - the compounds IDa.430 - IDa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where Rl~ ~ methyl, and Rll and Rl2 = trifluoro-- methyl:
0050/46586 CA 0224~6~9 1998-08-06 ~ . , .
_ H3C ~CH2- CH2--~--Y2Rl IDa Cl y3R2 10 - the compounds IDb.430 - IDb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rl1 and R12 - trifluoromethyl:
--~ Cl ~yl , ~N - N'~ CH2 CH - ~ y2Rl IDb Cl y3R2 - the compounds IDc.430 - IDc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~2 where R10 = methyl, and R1l and R12 ~ trifluoromethyl:
~ Br ~1 H C ~'N~CH2- CH - ~ y2Rl IDc f Cl y3R2 - the compounds IDd430 - IDd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where RlO = methyl, and Rl1 and Rl2 = trifluoromethyl:
CN yl ~N~N CH2--CH--! y2Rl IDd Cl y3R2 CA 022456~9 1998-08-06 c - the compounds IDe.430 - IDe.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~2 where R10 = methyl, and Rll and Rl2 = trifluoromethyl:
~=I~ CH3 yl ~N~N' ~ CH2 CH- P y2Rl IDe Cl y3R2 - the compounds IDf.430 - IDf.1287, which differ from the corres-lS po~ing compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~2 where Rl~ =
methyl, and Rll and R12 - trifluoromethyl:
CO ~-1 ~N'N' ~ CH2 CH - ~ y2Rl IDf Cl y3R2 - the compounds IDg.430 - IDg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2-ethenediyl and RS is the heterocycle ~2 where Rl~ = methyl, and Rll and Rl2 = trifluoromethyl:
__ F3C CF3 ~ ~ yl H3C ~ 'N ~ t \ I IDg R4 ~ CH CH - ~ y Cl y3R2 40 - the compounds IDh.430 - IDh.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth i8 -CH=C(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rll and R12 = trifluoromethyl:
_ _ , 77 ._ Cl yl -N ~ CH - C P YZRl IDh Cl y3R2 lO - the compounds IDi.430 - IDi.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rll and Rl2 s trifluoromethyl stehen:
~ Br yl (~' H3C N4 ~ CHC --~-- y2Rl IDi Cl y3R2 - the compounds IDj.430 - IDj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle <p2 where R10 = methyl, and Rll and R12 = trifluoromethyl:
~ CN yl ,N~ N' ~ CH C --" _ y2Rl IDj Cl y3R2 - the compounds IDk.430 - IDk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)-- and R5 is the neterocycie ~2 where R10 = rllethyl, ar.d Rll and R12 = trifluoromethyl.
CH3 yl N~N ~ ~:H C P y2Rl IDk \~/ I
C 1 ' y3R2 0050/465~6 - the compounds IDm.430 - IDm.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~2 where Rl0 = methyl, and R1l and R12 - trifluoromethyl:
F3C _~_____" CF3 lOH C ,N~ ~ CH C - ~ y2Rl IDm Cl y3R2 - the compounds IDn.~30 - IDn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C_C-and R5 is the heterocycle ~2 where Rl~ - methyl, and Rll and R12 = trifluoromethyl:
C ~ C -- C - ' - Y2R1 IDn Cl y3R2 - the compounds IEa.l - IEa.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that R5 is the heterocycle ~3 where Y4 2 oxygen, and Rl3 and Rl4 together = a tetramethylene chain:
(~': 0~~
~ ~ CH2 CH2- 1 - Y2Rl IEa Cl y3R2 40 - the compounds IEb.l - IEb.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~3 where Y4 - oxygen, and R13 and Rl4 together = a tetramethylene chain:
1~ Cl yl IEb ~ ~--CH2--CH P--Y2R
Cl y3R2 10 - the compounds IEc.l - IEc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CR2-CH(Br)- and R5 is the heterocycle ~3 where Y4 5 oxygen, and R13 and Rl4 together = a tetramethylene chain:
C ~C~--C~--r_y2~1 IEc Cl y3R2 - the compounds IEd.1 - IEd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~3 where y4 2 oxygen, and Rl3 and R14 together - a tetramethylene chain:
N\ CN yl R4~ CH2 CH - 7 - y2Rl IEd t \=~
Cl y3R2 - the compounds IEe.1 - IEe.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 together = a tetramethylene chain:
~ O
~N\ CH3 yl IEe R4~ CH2--CH--~--Y2R
~
Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 -- the compounds I~f.l - I~f.1287, which differ from the corres-~ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(COOCH3)-- and R5 is the heterocycle ~>3 where Y4 5 oxygen, and R13 and R14 together = a tetramethylene chain:
C ~ ;D OCH3 IEf R4 ~ CH2- CH - P - Y2R
Cl y3R2 - the compounds IEg.1 - IEg.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~)3 where Y4 = oxygen, and R13 and R14 together -- a tetramethylene chain:
~0 N~ -~1 IEg R4 ~ CH CH - ? _ y2Rl Cl y3R2 - the compounds IEh.1 - IEh.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~)3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ C3 = C - I - YZR~ I~h C 1 y3R2 40 - the compounds IEi.1 - IEi.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle q'3 where Y4 = oxygen, and R13 and Rl4 together = a tetramethylene chain:
OOSO/46586 CA 02245659 l998-08-06 ~ ~ C~ = C - ~ - Y~R1 IEi Cl y3R2 lO - the compounds IEj.1 - IEj.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN) - and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
15 ~
.~ ~ N CN yl IE;
~ ~CH -- C ~ Y2R
Cl y3R2 - the compounds IEk.l - IEk.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 25 -CH=C (CH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ \ CH3 yl IEk r R4--~-- CH = C ' y2 Cl y3R2 - the compounds IEm.l - IEm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ CO yl IEm R4 ~ CH = C ~ y2 Cl y3R2 OOSO/46586 CA 0224~6~9 1998-08-06 - the co...~ounds IEnl - IEn.1287, which differ from the corres-ponding c~ _~nds IAa.l - IAa.1287 only in that Eth is -C_C-and R5 iS the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 together 5 a tetramethylene chain:
~ O
N
Il \ yl IEn R4 ~ C C _ y2Rl Cl y3R2 - the compounds IFa.l - IFa.1287, which differ from the corres-ponding compounds IAa.l -- IAa.1287 only in that R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 - methyl:
H3C ~ o ~ N
20 H3C 11 \ yl IFa R4 - ~ CH2 CH2- ~ y2 Cl y3R2 - the compounds IFb.l - IFb.1287, which differ from the corres-ponding col--~ounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(Cl)--and RS is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 -- methyl:
H3C ~ O
~_ H3C ~ ~ ~ Cl yl IFb R4--~/ \ ~ CH2 CH ~ y Cl Y3RZ
- the compounds IFc.l - IFc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(Br)--and R5 iS the heterocycle ~P3 where Y4 = oxygen, and R13 and R14 = methyl:
~ . . . .
83 _ H3C ~ O
R4 ~ CH2 CH P _ y2R1 IFc Cl y3R2 10 - the compounds IFd.1 - IFd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2--CH(CN)--and Rs is the heterocycle q~3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ O
H3C \ CN yl IFd R4 ~ CH2 CH ~ y2 ~ y3R2 Cl - the compounds I~e.l - IFe.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(CH33-- and R5 is the heterocycle ~'3 where Y4 = oxygen, and R13 and Rl4 2 methyl:
H3C ~ O
H3C ~ ~ _ ~ CH3 yl IFe .~ R4 ~ CH2 CH ~ y2Rl Cl y3R2 - the compounds IFf.1 - IFf.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(COOCH3)-- and R5 is the heterocycle ~'3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ ~ OCH3 H3C ~ ~ CH2 CEi--P_ y2R1 IFf Cl y3R2 .
.
84 _ -- the compounds IFg.l -- IFg.1287, which differ from the corres--ponding compounds IAa.l -- IAa.1287 only in that Eth is 1,2--ethf-ne~liyl and R5 is the heterocycle ~P3 where Y4 = oxygen, and R13 and R14 = methyl:
5 H3C ~ O
H3C ~N\ yl IFg lOR4 ~ CH CH I Y2R
Cl y3R2 - the compounds IFh.l -- IFh.1287, which differ from the corres-15 pon-l;ng compounds IAa l -- IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~>3 where Y4 = oxygen, and R13 and Rl4 = methyl:
20H3C ~ffO
H3C ~~ \ Cl yl IFh 25R4~ CH -- C - P y C 1 y3R2 - the compounds IFi.l - IFi.1287, which differ from the corres--30 ponding cc,l..~ounds IAa l -- IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle tp3 where Y4 -- oxygen, and ~ R13 and R14 = methyl:
H3C ~O
H3C ~N~ Br -1 IFi R4 ~ CH - C " y Cl y3R2 - the compounds IFj.l -- IFj.1287, which differ from the corres--ponding compounds IAa.l -- IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ~I~3 where Y4 = oxygen, and 45 R13 and R14 = methyl:
.
_ H3C ~ O
~ N
H3C --1~ \ CN yl IF;
R4 ~ CH C ~ - Y2R
Cl y3R2 lO - the compounds IFk.l - IFk.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 iS the heterocycle ~3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ O
.~ - H3C ~ N CH3 yl IFk R4 ~ CH l - ~ - y2Rl ~
Cl y3R2 - the compounds IFm.1 - IFm.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 iS the heterocycle ~tp3 where Y4 = oxygen, and Rl3 and Rl4 3 methyl:
H3C ~ O OCH3 ~ N
H3C ~ CO yl IFm .. _ R4 ~ CH C - P y2 Cl y3R2 - the co.--~ounds IFn.1 - IFn.1287, which differ from the corres-ponding compounds IAa.l -- IAa~ 1287 only in that Eth is --C_C--and R5 is the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 e methyl:
H3C l~ ~ -11 IFn 45R4 ~ C _ C y2 C1 y3R2 0050/46586 CA 0224~6~9 l998-08-06 - the compounds IGa.1 - IGa.1287, which differ from the corres-ponding col--~ounds IAa.1 - IAa.1287 only in that R5 is the heterocycle ~4 where Rl5 and R16 together z tetramethylene chain and Rl7 = chlorine:
~ N
Cl \A yl IGa R4 ~ / \ ~ CH2 CH2- ~ - Y2R
~
Cl y3R2 - the compounds IGb.1 - IGb.1287, which differ from the corres-15 ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CR(Cl)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~ Cl \ Cl yl R4 ~ CH2 CH - ~- y2Rl IGb C 1 y3R2 - the compounds IGc.1 - IGc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
__ ~ N
~N~ Br yl Cl ~ CH2 CH _ y2Rl IGc Cl y3R2 40 - the compounds IGd.l - IGd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and RS is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
0050/46586CA 0224~6~9 l998-08-06 -~'~'~___N
N
~ CN yl R4 ~ -CH2 CH - P y2Rl IGd Cl y3R2 lO - the compounds IGe.1 - IGe.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
~'--~7___N
~ N
R4 ~ CH2 - C~ - ~ - y2Rl IGe Cl y3R2 - the compounds IGf.1 - IGf.1287, which differ from the corres-pbnding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
~ N l~cCo~3 yl Cl ~ CH2 - CH - I - Y2Rl IGf Cl y3R2 - the co...~ounds IGg.1 - IGg.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethene~;yl and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chsin and Rl7 = chlorine:
~ N
~ CH = C~ - ~ - Y~RI IGg Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 - the compounds IGh.l - IGh.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~~~ __N
~ Cl yl R4 ~ CH C - y2Rl IGh Cl y3R2 - the compounds IGi.l - IGi.1287, which differ from the corres-ponding co,..~ounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and R17 ~ chlorine:
~ N
~ N Br yl R4 ~ CH = C - P - YZRI IGi Cl y3R2 - the compounds IGj.l - IGj.1287, which differ from the corres-ponding co---~ounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
N
N
Cl \r-~ CN ~~1 IGj R4 ~ CH = C - ~ - y Cl y3R2 40 - the compounds IGk.l - IGk.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~i where Rl5 and R16 together = tetramethylene chain and R17 = chlorine:
~~~____N
~ ~, Cl ~I _ I _ y2Rl }Gk Cl y3R2 lO - the compounds IGm1 - IGm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~~~ __N OCH3 ~ N CO yl CH - C YZRl IGm Cl y3R2 - the compounds IGn.1 - IGn.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~4 where R15 and R16 together =
tetramethylene chain and Rl7 - chlorine:
N
N yl C C ~ y2Rl IGn Cl y3R2 - the compounds IHa.1 - IHa.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
0050/46~86 F2HC\ Cl N ~ /
H3C ~ \ l ~-1 IHa R4~ CH2 CH2 ? y2 Cl y3R2 - the compounds IHb.l - IHb.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~5 where Rl3 = chlorine, Rl9 - difluoromethyl and R20 8 methyl:
F2HC Cl H3C ~ \ ~ Cl -.1 \ I IHb R4~ CH2--CH ~ y2 Cl y3R2 - the compounds IHc.l - IHc.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~5 where R18 = chlorine, Rl9 s difluoromethyl and R20 - methyl:
~~ - F2HC\ Cl ~1 /
H3C ~ \ ¦ \ Br ~-1 R4 - ~ CH2 - CH ~ y2Rl IHc Cl y3R2 - the compounds IHd.l - IHd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and Rs is the he~erocycle ~5 where Rl3 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC\ Cl H3C~
N ~ CN ~1 IHd R4 ~ CH2 - CH ~ y Cl y3R2 - the compounds IHe.1 - IHe.1287, which differ from the corresponding ~ r~ounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
\ ~/
20 H3C ~ \ ~ CH3 ~rl IHe R4 ~ CH2 - CH - ' - Y2R
Cl y3R2 - the co..~ounds IHf.l - IHf.1287, which differ from the corresponding col..~o~nds IAa1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~5 where R18 =
chlorine, Rl9 = difluoromethyl and R20 = methyl:
--- F2HC Cl N ~ OCH3 H3C~,\ ~ CO ~rl IHf R4 ~ CH2 CH - ' YZR
Cl y3R2 - the compounds IHg.l - IHg.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~5 where Rl8 =
chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC Cl H3C ~ \ ~ yl ~ I IHg R4 ~ / \ ~ CH CH - ~ - y2R1 C 1 y3R2 - the compounds IHh.1 - IHh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~5 where R18 = chlorine, 15 R19 3 difluoromethyl and R20 = methyl:
F2HC Cl \ /
20 H3C ~ \ 3 Cl yl R4 ~ CH C- ~ - y2Rl IHh C 1 y3R2 - the compounds IHi.1 - IHi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth i~
-CH=C(Br)- and R5 is the heterocycle ~5 where R13 3 chlorine, R19 = difluoromethyl and R20 = methyl:
F2HC Cl H3C ~ \ ~ Br -rl IHi R4 ~ / \ ~ CH - C - ~ - y2Rl C 1 y3R2 - the compounds IHj.1 - IHj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 - difluoromethyl and R20 = methyl:
0050/46586 CA 0224~6~9 1998-08-06 ~. .
-N
H3C~
N- CN yl R4 _ ~ CH = C - ~ y2Rl IHj Cl y3R2 - the compounds IHkl - IHk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC\ Cl H3C ~ \ ¦ CH3 ~1 IHk R4 _ ~ CH - C - ~ y2 Cl y3R2 - the compounds IHm.l - IHm.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~5 where R18 =
chlorine, Rl9 - difluoromethyl and R20 = methyl:
F2HC Cl \ / OCH3 N-3C ~ \ ¦ CO -~1 I IHm R4 ~ CH = C - ~ - y Cl y8R2 - the compounds IHn.l - IHn.1287, which differ from the corresponding compounds IAal - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~5 where Rl8 c chlorine, Rl9 -difluoromethyl and R20 = methyl:
F2HC\ Cl N ~
H3C~\ I ~l I~n R4 ~ C C ~ - Y2R
Cly3R2 - the compounds IKa.1 - IXa.1287, which differ from the corresponding compounds IAa.1 -- IAa.1287 only in that R5 is the heterocycle ~7 where Y7 3 oxygen, and R23 and R24 together =
tetramethylene chain:
N'~N
yl IKa R4 ~ CH2 CH2- ~ - Y2R
C 1 y3R2 - the compounds IRb.1 - IKb.1287, which differ from the correspon~;ng compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(Cl)--and R5 is the heterocycle ~>7 where Y7 ~ oxygen, and R23 and R24 together = tetramethylene chain:
N'~N
O ~ Cl ~1 IRb R4 ~ CH2 CH - ~ y2 Cl y3R2 - the compounds IKc.1 - IKc.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(Br)--and R5 is the heterocycle ~7 where Y7 = oxygen, and 4S R23 and R24 together = tetramethylene chain:
, ._ ~ N Br ~rl O I IKc R4 ~ CH2 - CH y Cl y3R2 - the compounds IXd.l - IXd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2-CH(CN)-- and R5 is the heterocycle ~7 where Y7 ~ oxygen, and R23 and R24 together - tetramethylene chain:
~N ~ N
O CN --1 IKd R4 ~ CH2 - CH- ? y2 C 1 y3R2 - the compounds IRe.1 - IRe.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(CH3)-- and R5 is the heterocycle ~>7 where y7 2 oxygen, and R23 and R24 together c tetramethylene chain:
~N ~ N
~ N CH3 --1 O \ I IXe R4 ~ CH2 - CH ? - Y2R
Cl y3R2 - the compounds IKf.1 - IKf.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CHz--CH(COOCH3)-- and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
, 96 ._ N'--~N
~ N CO yl R4 ~ CH2 CH n y2Rl IRf Cl y3R2 - the compounds IKg.1 - IKg.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethene~l;yl and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together - tetramethylene chain:
N "~N
o~N ~~l IKg R4 ~ ~ CH CH . y2 Cl y3R2 - the compounds IKh.l - IKh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~P7 where Y7 = oxygen, and R23 and R24 together -- tetramethylene chain:
N N
o ~ N Cl yl R4 ~ CH ~ C P y2Rl IRh Cl y3R2 - the compounds IKi.1 - IKi.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C(Br)--and R5 is the heterocycle q~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
~ . .
~ N
o ~ N ~ Br yl IKi R4 ~ CR C - ~ y2 Cl y3R2 - the compounds IKj.l - IRj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ''P7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
N N
0N CN yl IKj R4 ~ CH - C ~ y Cl y3R2 - the compounds IKk.l - IKk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CR=C(CH3)-- and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
1 ~ N
, ~ N CH3 yl R4 ~ CH C "--y2Rl IKk Cl y3R2 - the compounds IKm.1 - IKm.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(COOCH3)-- and Rs is the heterocycle 'P7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
98 . _ N N
~N CO ~rl \ I IKm R4 ~ CH -- C--~~ y2 Cl y3R2 - the compounds IKn.l - IRn.1287, which differ from the correspo~;ng compounds IAa.l - IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~7 where Y7 z oxygen, and R23 15 and R24 together = tetramethylene chain:
~.
N N
1 IKn R ~ ~ C C - ~ - Y2Rl ~ .
Cl y3R2 - the compounds ILa.l - ILa.1287, which differ from the corresponding c~--l~ounds IAa.1 - IAa.1287 only in that R5 is the heterocycle ~20 where R50 - methyl, R5l = trifluoromethyl and R52 = hydrogen:
(~' ~
S ~ N - CH3 3S N -rl ~ - ILa R4 ~ CH2 - CH2 - y Cl y3R2 - the compounds ILb.1 - ILb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~20 where R50 = methyl, R5l ~ trifluoromethyl and R52 ~ hydrogen:
0050/46586 CA 0224~6~9 l998-08-06 ~ 99 ~ CF3 S~N CH3 R4~CH2 C~--I'_ y2Rl ILb Cl y3R2 - the compounds ILc.l -- ILc.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CH2--CH(Br)--and R5 is the heterocycle ~20 where R50 = methyl, 15 R5l -- trifluoromethyl and R52 = hydrogen:
~, ~ .
S~N-- CH3 N Br ~,l R4 ~ CH2--CH2--~--Y2Rl ILc Cl y3R2 - the compounds ILd.l -- ILd.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle ~p20 where R50 - methyl, 30 R51 -- trifluoromethyl and R52 8 hydrogen:
~' ~f S~N CH3 N CN ~1 ILd R4 ~ CH2 CH2--? _ y2Rl C 1 y3R2 - the compounds ILe.1 -- ILe.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is - --CH2--CH(CH3)-- and R5 is the heterocycle ~I~20 where R50 = methyl, 45 R5l = trifluoromethyl and R52 = hydrogen:
100 ' -S ~ N CH3 N CH3 yl R4 ~ CH2 CH- ~ y2Rl ILe Cl y3R2 - the compounds ILf.1 - ILf.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH~COOCH3)- and R5 is the heterocycle ~20 where R50 =
methyl, R5l = trifluoromethyl and R52 = hydrogen:
~' ~
S ~ N CH3 OCH3 N CO yl R4 ~ CH2 - CH ~ y2Rl ILf Cl Y3R2 - the c~...~ounds ILg.l - ILg.1287, which differ from the correspo~;ng compounds IAa.1 - IAa.1287 only in that Eth is 1,2--e~hene~l;yl and R5 i6 the heterocycle ~20 where R50 = methyl, R5l = trifluoromethyl and R52 = hydrogen:
~' ~
S ~ N CH3 N yl R4 ~ CH CH P Y2Rl ILg Cl y3R2 - the compounds ILh.1 - ILh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~20 where R50 - methyl, R5l = trifluoromethyl and R52 = hydrogen:
.
, 0050/46586 CA 0224~6~9 1998-08-06 S~,N CH3 N ~ Cl yl ILh R4 ~ / \ ~ CH - C ~ y Cl y3R2 - the compounds ILi.l - ILi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~20 where R50 = methyl, R51 = trifluoromethyl and R52 = hydrogen:
f ~
S ~ N CH3 N Br ~1 ~ I ILi R4 ~/ \ ~ CR - C - ~ y Cl y3R2 - the compounds ILj.l - ILj.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~20 where R50 = methyl, R51 - trifluoromethyl and R52 = hydrogen:
._ ~
S ~ N CH3 N CN ~-1 ~ I ILj R4 ~ CH - C -Cl y3R2 - the compounds ILk.l - ILk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~20 where R50 = methyl, R5l = trifluoromethyl and R52 = hydrogen:
~ .
S~N-- CH3 ~ I ILk R4--(/ \~ CH C ? y2 Cl y3R2 - the compounds ILm.l -- ILm.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CHsC(COOCH3)-- and R5 is the heterocycle ~20 where R50 = methyl, 15 R51 = trifluoromethyl and R52 - hydrogen:
_ CF3 ~, ~
S~N-- CH3 oCH3 N CO yl R4~ CH CH--~--y2Rl ILm Cl y3R2 - the compounds ILn.l -- ILn.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~20 where R50 s methyl, R51 =
30 trifluoromethyl and R52 ~ hydrogen:
1~ ~ .
S~N CH3 ILn R4 ~ C C - ~--Y2R
Cl y3R2 - the compounds IMa.l -- IMa.1287, which differ from the corresponding compounds IAa.l -- IA.1287 only in that R5 is the heterocycle ~21 where Z3 and Z4 = nitrogen, and R53 and R54 45 together = tetramethylene chain:
CA 0224~6~9 1998-08-06 .
N ~/
N ~ S
~ 5 N ~rl \ - IMa R4 ~ CH2 CH2- ' - Y2R
Cl y3R2 - the compounds IMb.l - IMb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
~, /~ O
.~ ~ ~N ~/
N~ ~ S
N Cl -~1 \ I IMb R4 ~ CH2 CH - ~ y2 Cl y3R2 - the compounds I~c.1 - IMc.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2-CH(Br)-- and R5 is the heterocycle q~21 where Z3 and Z4 =
nitrogen, and Rs3 and R54 together = tetramethylene chain:
/~ o ~N ~//
N ~ S
N Br .1 \ I IMc R4 ~ CH2 CH Y2R
Cl y3R2 - the compounds IMd.l - IMd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle q~21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
oo~o/46~86 CA 02245659 1998-08-06 .
.
~ ~ .
N y S
N CN yl R4 ~ CHz CH--P _ y2R1 IMd Cl y3R2 - the compounds IMe.1 - IMe.1287, which differ from the correspon~ing compounds IAa.l - IAa.1287 only in that Eth is --CHz--CH(CH3)-- and R5 is the heterocycle ~I>21 where Z3 and Z4 z nitrogen, and R53 and R54 together = tetramethylene chain:
. . /~ O
~N ~//
N ~ S
N CH3 yl \ I i IMe R4 ~ CH2 CH y Cl y3R2 - the compounds IMf.l - IMf.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(COOCH3)- and R5 iS the heterocycle ~Zl where Z3 and Z4 =
30 nitrogen, and R53 and R54 together -- tetramethylene chain:
/~ . O
f - ~, N ~/
N ~ S OCH3 11 l N CO yl I IMf R4 ~ CH2 CH - ~ y Cl Y3RZ
- the compounds IMg.l - IMg.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is 1,2--ethenediyland R5 is the heterocycle ~21 where Z3 and Z4 nitrogen, and R53 and R54 together = tetramethylene chain:
0050/46586 CA 0224~6~9 1998-08-06 105 ~
N ~//
N ~ S
Il N ~-1 \ IMg R4 ~ ~ CH CH- ? _ y2Rl Cl y3R2 - the compounds IMh.l - IMh.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(Cl)--and R5 is the heterocycle <~>21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
/~ O
~_ ~ /N ~
N ~ S
N\ Cl ~-1 R4 ~ ~ CE~ C--~ y2Rl IMh C 1 y3R2 - the compounds IMi.l - IMi.1287, which differ from the corresponding ~.~o~nds IAa.l - IAa.1287 only in that Eth is --CH-C(Br)-and R5 is the heterocycle ~p21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
N ~/
-- N ~ S
N Br yl R4 ~ CH C--~--y2Rl IMi Cl y3R2 - the compounds IMj.l - IMj.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(CN)-and R5 is the heterocycle tp21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
~ 0050/46586 CA 02245659 1998-08-06 .
'' 106 --/~ O
/ ~
N ~ S
N CN yl IMj R4 ~ CH - C ' y2 Cl y3R2 - the compounds IMk.l - IMk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(CH3)-- and R5 is the heterocycle ~>21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
/~ O
~N ~/~
N ~ S
N CH3 ~1 ~ I IMk R4 ~ CH C - ? _ y2 Cl y3R2 - the co",~ounds I~l - IM~1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle q~21 where Z3 and Z4 30 nitrogen, and R53 and R54 together = tetramethylene chain:
N ~
~ I
I IMm R4--~ ~ CH C - ? y2 Cl y3R2 - the compounds IMn.l - IMn.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -C_C- and R5 iS the heterocycle ~>21 where Z3 and Z4 = nitrogen, and R53 and R54 together = tetramethylene chain:
CA 02245659 l998-08-06 N //~
N ~ S
N -rl \ IMn R4 ~ C -- C --n y2Rl Cl y3R2 - the cGl..~ounds INa.1 - INa.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that R5 iS the heterocycle ~22 where R55 and R56 together = 2,2-dimethyl-propane-1,3-diyl chain:
H3C ~ N ~ S
N ~rl ~ INa R4 ~ ~ CH2--CH2-- '_ Y2R
Cl y3R2 - the compounds INb.1 - INb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
C H3C ~ N ~ ~N
N Cl yl R4 ~ C~2 CH - ~ y2Rl INb Cl y3R2 - the compounds INc.1 - INc.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
~ 0050/46586 CA 02245659 1998-08-06 ~ , 108 ~~
H3C ~ N ~ S
N Br --1 R4 ~ CH2 CH ; y2Rl INc Cl y3R2 - the ~ o~nds INd.l - INd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle ,~p22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ r==~N
N CN ~-1 R4 ~ CH2 CH - ~ y2Rl INd Cl y3R2 - the compounds INe.l - INe.1287, which differ from the corresponding co~l~ounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle <~22 where R55 and R56 together - 2,2-dimethylpropane-1,3-diyl chain:
_ H3C ~ N ~ S
~ CH3 ~~1 R4 ~ CH2 CH y2Rl INe Cl y3R2 - the compounds INf.l - INf.1287, which differ from the corresponding col-l~ounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(COOCH3)-- and R5 is the heterocycle ~p22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
.
H3C ~ ~N fCH3 \ I INf R4 ~ CH2 - CH2- ~ y Cl y3R2 - the compounds INg.1 - INg.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~22 where Rs5 and R56 together z 2,2-dimethylpropane-1,3-diyl chain:
~0~ -~1 INg R4 ~ CH - CH ~ y2 25Cl y3R2 - the col-,~ounds INh.1 - INh.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
~- H3C ~ N ~ ~N
35N Cl yl \ I I INh R4 ~ CH C - ~ y2 Cl y3R2 - the compounds INi.l - INi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
0050/46586 CA 02245659 l998-08-06 110 ' - ' 3C ~ N ~r R4 ~ CH - C _ y2R1 Cl y3R2 - the compound5 INj.1 - INj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~22 where R55 and Rs6 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ r--_N
H3C I N ~ S
N Br vl R4 ~ CH - C - ~ _ y2Rl INj Cl y3R2 - the compounds INk.l - INk.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ N
H3C I N ~ S
N\ CH3 i~l INk R4 ~ CH C ~ - y2 Cl y3R2 - the compounds INm.1 - INm.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
E33C ~ N ~ 5 oc~3 N CO '1 INm R4 ~ CH- C - ~ y2Rl C 1 y3R2 - the compounds INn.1 - INn.1287, which differ from the corresponding co...~ounds IAa.1 - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ N
~3C N S
~
N yl R4 ~ CC ' y2Rl INn Cl y3R2 The substituted aromatic phosphonic acid derivatives of the for-30 mula I are ob~;n~hle by a variety of routes, in particular byone of the following processes:
~- A) linkage of the phosphonyl group to the aromatic ring 35 A.l) by dia~otizing anilines II and reacting the resulting dia-zonium salts with vinyl- or alkynylphosphonic acid deriva-tives III by the Meerwein method {cf, for example, Org.
Reactions 11 (1960), chapter 3, pp. 189-260 and Kogyo Kagaku Zasshi 67(12) (1964), 2093-2095}:
-CA 0224~6~9 1998-08-06 Cl/Br diazotization ArNH2 yl ~ Ar--CH2 CH P--y + ~2C = CH - ~ Y2R1 ~salt ) y3R2 ~ Eth=CH2CHCl, CH2CHBr~
IIIa y3R2 Cl/Br yl --r I
ArNH2 diazotization 3 Ar - CH = C P - y2R1 + HC 3C LY2R1 G~) Y3R2 ¦ ~a J I~Eth=CH = CCl, CH - CBr 15IIIb y3R2 ~
_. / \
Ar ~ R4 ~
\ R3 /
In this method, the aniline of the formula II, which i8 either known from the literature or can be synthesized s;m;l~rly to An;l;nes known from the literature, is first converted into the corresponding diazonium cation in a ~-nner known per se, and this is then reacted completely with IIIa or IIIb in the presence of a copper salt.
The diazonium salt is generally obt~;n~ by reacting the C ~n; 1; ne II with a nitrite, such as sodium nitrite and potassium nitrite, in an aqueous acid solution, e.g. in aqueous hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid or tetrafluoroboric acid. The nitrite is normally employed in approximately equimolar amounts or in an excess of up to approximately five times the molar amount based on the amount of ~n; ~; ne II.
The resulting solution of the diazonium salt, or the diazo-nium salt isolated therefrom, is then reacted with a sol-ution or suspension of the vinyl- or alkynylphosphonic acid derivative IIIa/IIIb in the presence of a copper salt, such as copper(I) bromide~ copper(II) bromide copper( I ) chlor-ide and copper(II) chloride.
- 0050/46586 CA 0224~6~9 1998-08-06 .
Examples of suitable solvents are water, acetonitrile, ke-tones such as acetone, diethyl ketone and methyl ethyl ke-tone, ethers such as diethyl ether and tetrahydrofuran, and furth~-~ore alcohols such as methanol or ethanol.
The vinyl- or alkynylphosphonic acid derivatives IIIa/IIIb and the copper hA 1; ~e are normally used in approximately equimolar amounts or in an excess of up to approximately 30 times the molar amount based on the ~n;l;ne II. However, it is possible to employ a lesser or catalytic amount of the copper halide.
As a rule, the diazotization and the reaction of the diazo-nium salt with IIIa/IIIb are carried out at from (-100) to 50~C, preferably (-20) to +30~C.
One process variant consists in an addition to a solution or suspension of the aniline II, of the vinyl or alkynyl-phosphonic acid derivative IIIa/IIIb and of the copper halide in an anhydrous system, e.g. in glAc;~l acetic acid~
chlorohydrocarbon, absolute methanol or ethanol, in an ether such as tetrahydrofuran and dioxane or in aceto-nitrile or acetone, a nitrous ester such as tert-butyl ni-trite and isopentyl nitrite. What has been said above re-garding the reaction temperature and the ratios of the re-actants also applies here.
A.2) by means of a Heck reaction (see, for example, B. A. Buri-ni, S. Cacchi, P. Pace, B.R. Pietroni, Synlett 1995, 677):
Ra yl Ra yl ~5 Ar - ~Br +H2~=l , _ y2Rl bcaaSte~ Ar- CH = C P y2Rl y3R2 y3R2 IV V I~Ra = H, CN, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, ( Cl-C4-alkoxy )--carbonyl, di(Cl-C4-alkyl)-amino - 0050/46586 CA 0224~6~9 1998-08-06 ~s ,, As regards the definition of Ar, see Process A.1);
cat. is a transition-metal catalyst, preferably a palla-dium(II) compound such as palladium acetate.
As a rule, the reaction is carried out in an inert organic solvent, in particular in dimethylformamide or tetrahy-drofuran.
~xamples of suitable bases are carbonates such as potassium carbonate, acetates such as sodium acetate and tertiary amines such as triethyl A~; ne .
The reaction is generally carried out at from 0~C to the boiling point of the reaction mixture, preferably at 50 to 100~C.
~.
A.3) by means of Rnoevenagel condensation of aromatic aldehydes VIa or ketones VIb with phosphonic acid derivatives VII:
Ar- CHO (VIa) ~ + Rb_CH2 ,l_y2Rl~cat.
Ar- CO-(Cl-C4-alkyl) VIb ~ y3R2 VII H/Cl-C4-alkyl Ar c=f--P y2Rl Rb y3R2 ~~- As regards the definition of Ar, see process A.1);
b iS cyano, Cl-C4-alkoxy or (Cl-C4-alkoxy)carbonyl (VIIa ~ VII where Rb - CN; VIIb = VII where Rb = alkoxy);
cat. is a catalyst, e.g. piperidine/acetic acid, sodium methanolate, sodium ethanolate, titanium tetrachlo-ride/N-methylmorpholine, or chlorotri(isopropoxy)ti-tanium/triethyl A~i n~ .
The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a lower alcohol such as methanol and ethanol, or in a chlor-inated hydrocarbon such as dichloromethane.
- , 0050/46586 CA 0224~6~9 l998-08-06 115 _ The reaction temperature is generally at from 0~C to the boiling point of the reaction mixture.
If desired, the water which is freed during the reaction can be LeLI~ved by means of azeotropic distillation. In this case, the process is preferably carried out in an aromatic hydrocarbon such as ben7ene, toluene and the xylenes at the respective boiling point of the reaction mixture. {See, for example, S. Ab'lAllAh-El Ayoubi, F. Texier-Boullet, J. Hame-lin, Synthesis 1994, 258; D. Danion, R. Carrie, Tetrahedron Lett. 1968, 453?; F. Texier-Boullet, A. Foucaud, Tetrahe-dron Lett. 21 (1980), 2161; S. Patai, A. Schwartz, J. Org.
Chem. 25 (1960), 1232; J.M. McIntosh, R.A. Sieler, Can. J.
Chem. 56 (1978), 226; M.T. Reetz, R. Peter, M. v. Itzstein, - Chem. Ber. 120 (1987) 121; R.A. Petrov, V.A. Chauzov, S.V.
Agafonov, N.V. Pazhitnova, J. Gen. Chem. USSR 50 (1980), 1225}.
Those aromatic aldehydes VIa or ketones VIb which are not already known can be prepared in a manner known per se.
A.4) by means of Wittig-Horner olefination {cf., for example, B.M.G.T. Lowen, M.R. Almond, J. Org. Chem 59 (1994) 4548;
P. Teulade, P. Savignac, E.E. Aboujaoude, S. Lietge, N.
Collignon, J. Org~nt -L. Chem. 304 (1986), 283; G.M. Par-ratt, J. Chem. Soc., Perkin Trans. 1 (1986), 1417; B.
Costisella, I. Reitel H. Gross, Tetrahedron 37 (1981), 1227}:
Ar CHO (VIa) C- - ~- y VIb R~ y3R2 /
VIII
H/Cl--C~l yl I Ar - C = C y RC y3R2 - As regards the definition of Ar, see process A.1);
RC is hydrogen, halogen, Cl-C4-alkyl or di(Cl-C4-alkyl)amino (VIIIa = VIII where Rc = H;
VIIIb = VIII where Rc = halogen; VIIIc = VIII where Rc = alkyl).
-, 0050/46586 CA 0224~6~9 l998-08-06 The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a halogenated hydrocarbon such as dichloromethane or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
The anion VIII can be obtained, for example, by deprotonat-ing the corresponding methanediphosphonic acid derivative with a strong base such as lithium diisopropyl ~m j ~ ~ sodium hydride and n-butyllithium.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at lS from (-78) to +30~C.
- A.S) by means of Wittig olefination {see, in this context, for example GB-A 12 43 214~:
Ar - CH0 (VIa) ' + Ph3P = CH - y Ar - C0 - (C1-C4-alkyl) VIb J -~3R2 H/Cl-C4-alkyl V
~-Ar C = CH y I y3R2 As regards the definition of Ar, see process A.l);
Ph is the phenyl group.
The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a halogenated hydrocarbon such as dichloromethane or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from 20 to 60~C. -- ~ OO~O/46586 CA 02245659 1998-08-06 A.6) by means of Peterson olefination {see, in this context, for example O.I. Kolodyazhnyi, D.B. Golokhov, J. Gen. Chem.
USSR 57 (1987), 2353; F.A. Carey, A.S. Court, J. Org. Chem.
37 (1972), 939}:
Ar-CHO (VIa) H ~ -alkyl Ar_CO _ alkyl*) (VIb) ¦
10 Ar_ CO - haloalkyl~) (VIc) ~CR2 ~--Y2R
Ar- CO - dialkyl~)amino (VId) X y3R2 strong base, ~ (C~3)3SiCl ._~
R/Cl-C4-alkyl I y Ar - C = C - P y y3R2 ~)each Cl-C4 Htalkyl~) haloalkyl~) I
dialkyl*)amino The process is norr-lly carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
Examples of suitable strong bases are lithium diisopropyla-mide, sodium hydride or butyllithium.
In general, the reaction is carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from (-70) to +30~C.
Preferably, X is ~irst reacted with chlorotrimethylsilane in the presence of a strong base, and only then is the reaction product treated with a compound VIa to VId. As a 4S rule, the base is used in an excess, approximately 2 to 5 times, in particular approximately 2 times, the molar amount based on the amount of X. Chlorotrimethylsilane is . ~ 0050/46586 CA 0224~6~9 l998-08-06 :
expediently employed in an approximately equimolar amount based on the amount of X.
Those aromatic aldehydes VIa, ketones VIb and VIc and the N,N-dialkylbenz~m;~es VId which are not already known can be prepared in a m~nner known per se.
A.7) by means of subjecting a styryl h~l ;Ae XI to a coupling reaction with a trialkyl phosphite XII or a dialkyl phos-phite XIII {cf. in this context, for example, R.S. Gross, S. Mehdi, J.R. McCarthy, Tetrahedron Lett. 34 (1993), 7197;
G. Axelrad, S. Laosooksathit, R. Engel, J. Org. Chem. 46 (1981), 5200}:
-- PtO(C1-C4-alkyl)]3 Br XII
Ar C = C - I
1 1 ~ or Rd Re Hpoto(cl-c4-alkyl)]2 XI
,XIII ~ \
~1 o Ar C = C - P O(C1-C4-alkyl) ld le O( Cl--C4--alkyl ) I (y1~y2~y3 = o) c As regards the definition of Ar, see process A.1);
Rd and Re are hydrogen, halogen or Cl-C4-alkyl.
The process is nor~-lly carried out in an inert organic solvent, preferably in an aromatic hydrocarbon such as toluene or an ether such as tetrahydrofuran.
The reaction of XI with a trialkyl phosphite XII is advan-tageously carried out in the presence of copper(I) b or copper(I) chloride.
~ 0050/46586 CA 0224~6~9 l998-08-06 The reaction of XI with a dialkyl phosphite XIII is advan-tageously carried out in the presence of a transition-metal catalyst, preferably a palladium(II) compound, such as dichlorobis(triphenylphosphine)palladium, and, if desired, in the presence of a base, e.g. triethylamine.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at approximately +25~C.
Those styryl h~ es XI and phosphorus compounds XII and XIII which are not already known can be prepared in a ~-nner known per se.
A.8) by reacting a phenylacetylene XIV
- with a trialkyl phosphite XII or - in succession with phosphorus pentachloride and an alcohol, mercaptan or amine (HY2Rl/HY3R2) in the pres-ence of a base ~cf. in this context, for example, C.E. Griffin, T.D.
Mitchell, J. Org. Chem. 30 (1965), 1935; A. Meisters, J.M.
Swan, Aust. J. Chem. 18 (1965), 155; L. Maier, Synth.
Inorg. Met. Org. Chem. 3 (1973), 329; A.A. Petrov, J. Gen.
Chem. USSR 41 (1971) 1670}:
~ or XII or Ar - C-C - ~cl-c4-alkyl 1) PCl5 2) RY
XIV or HY3R2 ~ H/Cl P(O~ -O(Cl-C4-alkyl)l ~ ' - J 2' 35Ar - C = C P(O)(Y2Rl)(y3R2) I ~ ~ I Eth= ethenediyl, I chloroethene-H/C1-C4-alkyl diyl As regards the definition of Ar, see process A.1).
XIV is preferably reacted with XII in the absence of a sol-vent at from 20~C to the boiling point of the trialkyl phosphite XII, in particular at the boiling point of the reaction mixture.
. ~ 0050/46586 CA 0224~6~9 l998-08-06 Suitable bases for reacting the phenylacetylene XIV with PCl5 and (HY2Rl/HY3R2) are, in particular, tertiary ~mine~
such as pyridine and triethyl~mi ne.
XIV is preferably reacted with PCls at from 50 to 200~C, in contrast to the subsequent reaction with (HY2Rl/HY3R2), where the reaction temp~rature is from (-100)~C to the boiling point of the reaction mixture.
Those phenylacetylenes XIV and the alcohols, mercaptans and ~ineS (HY2Rl/HY3R2) which are not already known can be pre-pared in a ~Anner known per se.
15 A.9) by reacting benzyli~enetriphenylphosphoranes XV with a per-fluoroAlk~necarboxylic anhydride and subsequently with a lithium dialkyl phosphite in a ~onner known per se {cf. in ~- this context, for example, Y. Shen, Q. Liao, W. Qiu, J.
Chem. Soc., Perkin Trans l, 695 (l990)}:
20 P(Ph)3 (F3C-C02)0~ lithium dialkyl-)~ H or (F3C-CF2-C0)20 phosphit \
Ar ~Cl-C4-alkyl XV H/Cl-C4-alkyl 0 Ar C = IC P O(Cl-C4-alkyl) o ( cl-c4-alkyl, I ~yl~y2~y3 = o~ CF3/C2F5 As regards the definition of Ar, see process A.1);
Ph is the phenyl group.
Suitable solvents~diluents for XV are, in particular, aro-matic hydrocarbons, such as toluene and ethers such as tetrahydrofuran.
The reaction can generally be carried out at ~rom ~-100)~C
to the boiling point of the reaction mixture, preferably at from (-78) to +25~C.
Those benzylidenetriphenylphosphoranes XV which are not already known can be prepared in a ~onne~ known per se.
. ~ 0050/46586 CA 0224~6~9 1998-08-06 A.10) by alkylating a phosphonic acid derivative XVI with a 3-pyridylbenzyl h~ e XVII in a mAnn~r known per se in the presence of a strong base {cf. in this context, for example, G.M. Blackburn, M.J. Parratt, J. Chem. Soc., Per-kin Trans 1 (1986), 1425; G.M. Rosolapoff, J.S. Powell, J.
Am. Chem. Soc. 72 (1950), 4198; R.M. Keenan et al., J. Med.
Chem. 3S (1992), 3858; H. Ahlbrecht, W. Farnung, Synthesis 336 (1977); E. D'Incan, J. Seyden-Penne, Synthesis, 516 (1975); S. Hanessian, Y.L. Benn~ni~ D. Delorme, Tetrahedron Lett. 31 (1990), 6461}:
~-1 Ar - CH2 ~Br + Rf - CH2 - " y2Rl strong (I base _ XVII XVI y3R2 Rf yl I~X ehtlhane Y C CY4 aikyl-, Ar CH2 - 1H - ~_ Y2R1 (Cl-C4-alkoxy)carbonyl- or di-(Cl-C4-alkyl)amino- y3R2 subst. ethanediyl~
As regards the definition of Ar, see process A.l;
Rf is hydrogen, cyano, halogen, Cl-C4-alkyl, (Cl-C4-alkoxy)carbonyl or di(Cl-C4-alkyl)amino (XVIa = XVI where Rf - CN; XVIb = XVI where Rf = alkyl).
Examples of suitable strong bases are sodium hydroxide, - butyllithium and lithium diisopropylamide.
The process is usually carried out in an inert organic sol-vent, preferably in an aromatic hydrocarbon such as toluene or a cyclic ether such as tetrahydrofuran.
The process is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably from (-78)~C to 25~C.
Those phosphonic acid derivatives XVI and benzyl halides XVII which are not already known can be prepared in a ~nner known per se.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 A.ll) by reacting phenylacetaldehydes XVIII with dialkyl phos-phites XIII, if desired in the presence of ammonia or of a primary or secondary amine {cf. in this context, for example, M.E. Ch~lm~rs, G.M. Kosolapoff, J. Am. Chem. Soc.
75 (1953), 5278; C. Li, C. Yuan, Tetrahedron Lett. 34 (1993), 1515}:
OH O
10 Ar - CH2 CHO 3 Ar - CH2 1H - - O ( C1-C4_a1kY1 ) (XVIII) O(Cl-C4-alkyl) I ~ Eth = hydroxyethylene; yl~y2~y3 =
,~ O
XVIII +XIIINH3(c C( alk4yl) Y~ Ar CH~ 7H 7 - O(Cl-C4-alkyl) (H/Cl-C4-alkyl)2N O(Cl-C4-alkyl) ( Eth = -CH2-CH(NH2)-~ ) I ~ -CH2-CH[NH(Cl-C4-alkyl)~
~ -CH2-CH [ N(Cl-C4-alkyl) 2 ~ _; yl, Y2, y3 = O>
As regards the definition of Ar, see process A.l).
Examples of suitable solvents are water, the lower alcohols such as methanol, ethers such as tetrahydrofuran and die-thyl ether, and pyridine.
The process is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably from 20 to 50~C.
Those phenylacetaldehydes XVIII which are not already known can be prepared in a m~nn~r known per se.
A.12) by reacting alkyl h~ es XIX with trialkyl phosphites XII
in a l'nn~r known per se following Arbuzov's method {see in this context, for example, A.Y. Garner, E.C. Chapin, P.M.
Scanlon, J. Org. Chem. 24 (1959), 532}:
- ~ 0050/46S86 CA 0224~6~9 1998-08-06 .
Ar - CR CH2 ~3r + XII
IJ
O
H/Cl-C4--alkyl Ar CH CH2 - ~'- O(Cl-C4-alkyl XIX
~_ O(Cl-C4-alkyl) H/Cl-C4-alkyl I ~ Eth = -cH2-cH2 -cH(cl-c4-alkyl)-cH2-; yl~y2~y3 =
, As regards the definition of Ar, see process A.1).
The reaction is preferably carried out in the absence of a solvent, suitable reaction t~reratures being from 0~C to the boiling point of the trialkyl phosphite XII, preferably from 20 to 150~C.
Those alkyl hA 1; ~S XIX which are not already known can be prepared in a m~nnPr known per se.
A.13) by reacting an aldehyde VIa with a trichloromethanephos-phonic acid derivative XXVI in the presence of an alkyl-lithium compound XXVII
yl ll (Cl-C4-alkyl)-Li Ar- CH0 + C13C p__ Y2Rl ~ I~X = -CH=C(Cl)-~
VIa I XXVII
y3R2 XXVI
As regards the definition of Ar, see process A.1).
Normally, the trichloromethanephosphonic acid derivative XXVI is first reacted with the alkyllithium compound XXVII
in an inert organic solvent, for example an ether such as tetrahydrofuran or a hydrocarbon such as n-hexane. The process is generally carried out between the melting point - ~ 0050/46586 CA 0224~6~9 1998-08-06 .
and the boiling point of the reaction mixture, preferably at from (-80) to (-50)~C.
The reaction product is then reacted with the aldehyde VIa - preferably without prior work-up -, the reaction temperature preferably being raised to approximately +20~C.
B) Derivatization of substituted aromatic phosphoric acid derivatives of the formnl~ I
As regards the reaction procedure and the ratios of the reactants, reference may be made, for example, to Houben-Weyl, Methoden der Organischen Chemie tMethods in Organic Ch~-ictry]~ Georg Thieme Verlag, Stuttgart, Vol. 12/1, 4th Edition 1963, p. 387 et seq., 407 et seq. and 557 et seq.;
~r Vol. E2 1982, p. 300 et seq. and 419 et seq.
B.l) Hydrogenation of substituted aromatic phosphonic acid derivatives I where Eth is ethene-1,2-diyl or a halogen-substituted ethane-1,2-diyl bridge {cf., for example, C.N.
Robinson, P.K. Li. J.F. Addison, J. Org. Chem. 37 (1972), 2939; G.T. Lowen, M.R. Almo~, J. Org. Chem. 59 (1994), 4548}:
I~Eth= unsubst. or subst. 1,2- I{Eth=unsubst. or eth~ne~iyl or chlorine-, subst.
bromine- or io~i ne - 1,2-ethane-substituted 1,2-ethane ' ~ ' diyl}
diyl, to which further subst. may be attached if desired~
'~' ' As regards the definition of Ar, see process A.1).
The hydrogenation is carried out either using hydrogen in the presence of a catalyst customary for this purpose, such as palladium or platinum on active charcoal or Raney nickel, at from 0 to 150~C and a hydrogen pressure of approximately 1 to 200 bar, or using a metal hydride such as sodium borohydride and lithium alu~in-lm hydride, at from 0~C to the boiling point of the reaction mixture.
Examples of solvents which are suitable for the hydrogena-tion using hydrogen are water, the lower alcohols, such as methanol and ethanol, ethers such as diethyl ether and tetrahydrofuran or esters such as ethyl acetate.
0050/46586 CA 0224~6~9 1998-08-06 . 125 When reacting the starting compound with a metal hydride, ~ the process is preferably carried out in an inert organic solvent, in particular an ether such as diethyl ether and tetrahydrofuran.
B.2) Hydrolysis of substituted aromatic phosphonic acid deriva-tives I, conversion of the process products into phosphonyl halides, and reaction thereof with nucleophiles:
O
hydro- ¦
Ar- Eth- ORl i~ Ar- Eth- o~ 3 Ar- Eth- ~-Cl-~ -I{Y1=O}
oR2 OH Cl lS I {yl,y2,Y3 = O} I {Yl,Y2,Y3=o;Rl,R2=H} XXIVa C hydrolysis ~
O
Ar- Eth-.'- oRl Ar - Eth - ~--oR1 ~ I {yl,y2=O}
OH Cl I {yl,y2,Y3=O; R2=H} XXVa ~,S S
Ar- Eth- ~- Cl- ~- XXIVa-~ -Ar- Eth-. ORl ~ Ar - X -.'-30Cl OH Cl XXIVb I {Y=S;Y2,Y3=o;R2=H} XXVb ~ ~
I {Yl=S} I {Yl=S; y2=o}
40As regards the definition of Ar, see process A.l).
.
In this process, the substituted aromatic phosphonic acidderivatives I are first cleaved hydrolytically (acidic or basic) or, in the event that Rl and/or R2 is a benzyl or allyl radical, also hydrogenolytically to give phosphonic acids and phosphonic monoesters I. If desired, the cleavage can also be carried out by means of reaction with a . ~ 0050/46586 CA 0224~6~9 1998-08-06 .
tri(Cl-C4-alkyl)silyl halide, such as chlorotrimethyl-silane, iodotrimethylsilane, or a mixture of chlorotri-methylsilane and an alkali metal iodide.
The cleaved products can then be converted into the corre-sponding phosphonylmono- or -dichlorides XXIVa and XXVa by reacting them with a halogenating agent such as oxalyl chloride, thionyl chloride or phosphorus pentachloride.
If desired, the phosphonyl dichlorides XXIVa can be sulfur-ized in a ~nner known per se using a sulfurizing agent, such as phosphorus(V) sulfide and 2,4-bis(4-methoxyphe-nyl)-1,3,2,4-di~h;~;rhosphetane-2,4-dithione ("Lawesson~s reagent") to give thionophosphonyl dichlorides XXIVb. As regards suitable solvents, t~mr~rature and ratios, mention may be made of what has been said in DE-A 19 504 188 under process D).
~Finally, other substituted aromatic phosphonic acid deriva-tives I are accessible by reacting XXIV and XXV with nucleophiles HY2Rl or HY3R2.
The phosphonic acid monoester chlorides XXVa can be con-verted into the thionophosphonic acid monoesters XXVb, for ex_mple by reaction with sodium hydrogen sulfide.
B.3) El;~;nAtion of hydrogen halide from compounds I where Eth = -CH2-CH(halogen)- or -CH=C(halogen)-:
C I {Eth z -CH2-CH(halogen)-} i I {Eth = -CH=CH-}
I {Eth 5 -CH=C(halogen)-} base I {Eth = -C~C-}
The process is normally carried out in water or an inert organic solvent, e.g. an alcohol such as ethanol, an ether such as diethyl ether, tetrahydrofuran and dioxane, or an aprotic solvent such as acetonitrile, dimethylformamide and dimethyl sulfoxide.
Examples of suitable bases are A lk~l; metal hydroxides, alkali metal carbonates, alkali metal hydrides, alkyllithium compounds such as butyllithium, or organic amines such as triethylamine, . ~ 0050/46586 CA 0224~6~9 l998-08-06 1,4-diazabicyclot2.2.2.]-octane (DABC0) and 1,8-diazabicyclor5.4Ø]undec-7-ene (DBU).
As a rule, the reaction is carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from 20 to 100~C.
C) Synthesis of the heterocycles Rs:
10 C.1) Synthesis of the triazolopyridine ring ~ NH H2N - ~H yl 15 R24 - N + R4 ~ Eth - P - y - o - (Cl-C4-alkyl) R3 Y3R2 XXIX XXVIII
N ~\ ~ base y o NH yl (Cl-C4-alkyl) R4 ~ Eth - p - y2Rl XXX
acid C
I (R~ = ~7 In this process, an amidine of the formula XXIX or an acid addition salt thereof (for example the hydrochloride, hydrobromide or hydrogen sulfate thereof) is reacted with a phenylhydrazine of the formula XXVIII or an acid addition salt thereof (for example the hydrochloride, hydrobromide or hydrogen sulfate thereof) in the presence of a base, for example an A1k~li metal acetate, alkali metal hydrogen carbonate, alkali metal carbonate or alkali metal hydroxide or a tertiary amine such as triethylamine.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 As a rule, the reaction is carried out in an inert organic solvent, e.g. an ether such as tetrahydrofuran, an alcohol such as ethanol, or an aprotic solvent such as dimethylformamide, acetonitrile or dimethyl sulfoxide.
As a rule, the reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 50~C.
The reaction product XXX is then cyclized in an inert organic solvent! e.g. a hydrocarbon such as toluene or n-hexane, an ether such as tetrahydrofuran, an alcohol such as ethanol, a carboxylic acid such as acetic acid, or an aprotic solvent such as dimethylform~m;~, acetonitrile or dimethyl sulfoxide, in the presence of an acid, for example acetic or hydrochloric acid.
. . .
Again, the cyclization is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
C.l.l)Preparation of the phenylhydrazines XXVIII from Anilines of the formula XXXI:
E~2N yl ~ ll 1) diazotization R4 ~ / \ ~ Eth - P - Y2R1 3 XXVIII
~ 1 2) reduction 30 \ y3R2 R
C XXXI
In this process, the aniline XXXI is first diazotized. In this context, reference may be made to the information given above for A.1).
The resulting diazonium salt is reacted with a reducing agent, for example a tin(II) compound such as tin(II) chloride in an inert solvent/diluent, e.g. a hydrocarbon such as toluene or n-he~ne, an ether such as tetrahydrofuran, an alcohol such as ethanol, an acid such as acetic acid and hydrochloric acid, an aprotic solvent such as dimethylforr-~;de, acetonitrile and dimethyl - sulfoxide, or in water. The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 Especially preferred phenylhydrazines of the form~ XXVIII
are listed in Table 2 below.
Table 2 H2N NH yl R4 ~ Eth P y2Rl XXVIII
No. R3 R4 -Eth-P(=yl)(y2Rl)(y3R2) XXVIII.l Cl H -CH2-CH2-P(=O)(OCH3k XXVIII.2 Cl Cl -CH2-CH2-P(=0)(0CH3)z XXVIII.3 Cl F --CH2-CH2--P(=0)(0CH3k XXVIII.4 Cl H -CH2-CH2-P(=O)(OC2Hs)2 XXVIII.5 Cl Cl -CH2-CH2-P(=O)(Oc2Hs)2 XXVIII.6 Cl F -CH2-CH2-P(=O)(OC2Hs)2 XXVIII.7 Cl H -CH2-CH(Cl)--P(=O)(OCH3)2 2 5 xxvm.8 Cl Cl -CH2-CH(Cl)--P(=O)(OCH3)2 XXVIII.9 Cl F --CH2-CH(Cl)--P(=O)(OCH3)2 XXVIII.10 Cl H -CH2-CH(Cl)--P(=o)(oc2Hs)2 XXVIII.ll Cl Cl -CH2-CH(Cl)--P(=O)(OC2Hs)2 XXVm.12 Cl F --CH2--CH(Cl)--P(=O)(OC2Hs)2 XXVIII.13 Cl H -CH2-CH(Br)-P(=O)(OCH3)2 C ~VIII.14 Cl Cl -CH2-CH(13r)-P(=O)(OCH3)2 XXVIII.lS Cl F -CH2-CH(Br)-P(=O)(OCH3)2 3 5 XXVIII. 16 Cl H -cH2--cH(Br)-p(=o)(oc2Hs)2 XXVIII.17 Cl Cl -CH2-CH(I3r)-P(=O)(OC2Hs)2 XXVIII. 18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2 XXVIII.l9 Cl H -CH2-CH(CN)-P(=O)(OCH3)2 XXVIII.20 Cl Cl --CH2-CH(CN)-P(=O)(OCH3)2 XXVIII.21 Cl F -CH2-CH(CN)--P(=O)(OCH3)2 XXVIII.22 Cl H --CH2-CH(CN)--P(=O)(Oc2Hs) ~VIII.23 Cl Cl -CH2-CH(CN)-P(=O)(OC2Hs) XXVIII.24 Cl F -CH2-CH(CN)-P~=O)(OC2Hs) XXVIII.25 Cl H --CH=CH-P(=O)(OC~)2 XXVIII.26 Cl Cl -CH=CH-P(=O)(OCH3)2 - ~0050/46586 CA 02245659 l998-08-06 .
No. R3 R4 -E~-P(=yl)(y2Rl)(y3R2)~X~II.27 Cl F -cH=cH-p(=o)(ocH3)2 ~X~II.28 Cl H -CH=CH--P(=o)(oc2Hs)2 5~XVIII.29 Cl Cl -CH=CH - P(=O)(OC2Hs)2 ~X~II.30 Cl F -CH=CH--P(=O)(OC2Hs)2 ~XVI~.31 Cl H -CH=C(CI)-P(=O)(OCH3)2 ~X~nlI.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 10~X~II.33 Cl F -CH=C(CI)-P(=O)(OCH3)2 II.34 Cl H -CH=C(CI)-P(=O)(OC2Hs)2 ~VD~.35 Cl Cl -CH=C(Cl)--P(=o)(oc2Hs)2 ~Y~II.36 Cl F -CH=C(Cl)--P(=O)(OC2Hs)2 15~X~II.37 Cl H -CH=C~Br)-P(=O)(OCH3)2 ~VI~.38 Cl Cl -CH=C~Br)-P(=O)(OCH3)2 ~XVIU.39 Cl F -cH=c~Br)-p(=o)(ocH3)2 ~XV~II.40 Cl H- -CH=C~Br)-P(=O)(OC2H5)2 20~XVIII.41 Cl Cl -CH=C~Br)-P(=O)(OC2Hs)2 ~XVI~.42 Cl F -cH=c~Br)-p(=o)(oc2Hs)2 ~XVIII.43 Cl H -CHSC(CN~-P(=0)(OCH3)2 ~XVD~.44 Cl Cl --CH=C(CN~-P(=O)(OCH3)2 25~XVD~.45 Cl F -CH=C(CN~--P(=O)(OCH3)2 ~XVIL46 Cl H -CH=C(CN~--P(=o)(oc2Hs)2 ~XVI~.47 Cl Cl -CH=C(CN~-P(=O)(OC2Hs)2 ~YVI~.48 Cl F -CH=C(CN~-P(=O)(OC2Hs)2 30 C.1.2)Preparation of the ~n;l;nes XXXI by reducing nitrobenzene derivatives XXXII:
.
~'_.- 02N yl ~ ll reduction 35 R4 ~ / \ ~ Eth P Y2R1 3 XXXI
\=~ I
XXXII
The reduction can be carried out with a metal such as iron, zinc or tin under acidic reaction conditions, or with a complex hydride such as lithiumaluminum hydride and sodium borohydride, examples of solvents being water, alcohols such as methanol, ethanol and isopropanol, or ethers such as diethyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran and ethylene glycol dimethyl ether, depending on the chosen reducing agent.
- , 0050/46586 CA 0224~6~9 1998-08-06 If the reduction is carried out with a metal, this is preferably performed in the absence of a solvent in an inorganic acid, in particular in concentrated or dilute hydrochloric acid, or in an organic acid such as acetic acid. However, it is also possible to admix an inert solvent, e.g. one of those mentioned above, with the acid.
The amount of acid is not critical. In order to reduce the starting compound as completely as possible, it is expedient to use at least an equivalent amount of acid.
The reaction temperature is generally at from (-30) to 200~C, preferably at 0 to 80~C.
The nitro group of the compounds XXXII may also be ~~ hydrogenated catalytically using hydrogen. Examples of - catalysts which are suitable for this purpose are Raney nickel, p~ ;um-on-charcoal~ palladium oxide, platinum and platinum oxide, an amount of catalyst of from 0.05 to 10.0 mol% based on the compound to be reduced generally being sufficient.
The process is either carried out in the absence of a solvent or in an inert solvent or diluent, e.g. in acetic acid, a mixture of acetic acid and water, ethyl acetate, ethanol, or in toluene.
After the catalyst has been ~ ,ved, the reaction solution can be worked up as usual to give the product.
~' The hydrogenation can be carried out under atmospheric pressure or under elevated pressure.
Especially preferred ~n; lines XXXI are listed in Table 3 below.
Table 3 H2N yl R4 _ ~ Eth - P - y2Rl XXXI
R3 y3R2 No. R3R4 -Eth-p(=yl)(y2Rl)(y3R2) X~.l Cl H -CH2-CH2--P(=O)(OCH3)z X~I.2 Cl Cl -CH2-CH2--P(=O)(OCH3)2 X~I.3 Cl F -CH2-CH2-P(=O)(OCH3)2 X~I.4 Cl H -CH2-CH2--P(=~)(~C2Hs)2 X~I.S Cl Cl -CH2-CH2-P(=O)(Oc2Hs)2 X~.6 . Cl F -cH2-cH2-p(=o)(oc2Hs)2 X~.7 Cl H -CH2-CH(Cl)--P(=O)(OCH3)2 X~I.8 Cl Cl -CH2-CH(Cl)-P(=O)(0CH3)2 X~.9 Cl F -CH2-CH(Cl)-P(=O)(0C~3)2 X~I.10 Cl H -CH2-CH(Cl)--P(=O)(OC2Hs)2 XXXI.ll Cl Cl -CH2-CH(Cl)--P(=o)(oc2Hs)2 X~.12 Cl F -cH2-cH(cl)-p(=o)(oc2H5)2 f X~I.13 Cl H -CH2-CH(Br)-P(=O)(OCH3)2 X~.14 Cl Cl -cH2-cH(Br)-p(=o)(ocH3)2 XXXI.lS Cl F -CH2-CH(Br)-P(=O)(OCH3)2 X~I.16 Cl H -cH2-cH(Br)-p(=o)(oc2Hs)2 X~. 17 Cl Cl -cH2-cH(Br)-p(=o)(oc2Hs)2 X~I.18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2 XXXI.l9 Cl H -CH2--CH(CN)-P(=O)(OCH3)2 X~.20 Cl Cl -CH2--CH(CN)-P(=O)(OCE~)2 X~I.21 Cl F -CH2-CH(CN)-P(=O)(OCH3)2 X~.22 Cl H -CH2--CH(CN)-P(=O)(OC2Hs)2 X~.23 Cl Cl -CH2-CH(CN)-P(=O)(OC2Hs)2 X~I.24 Cl F -cH2-cH(cN)-p(=o)(oc2H5)2 ~- X~.25 Cl H -CH=CH-P(=O)(OCE~3)2 X~.26 Cl Cl -CH=CH-P(=O)(OCH3)2 X~.27 Cl F --CH=CH-P(=O)(OC~3)2 X~I.28 Cl H -CH=CH-P(=O)(OC2Hs)2 X~.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~I.30 Cl F -CH=CH--P(=o)(oc2Hs)2 X~.31 Cl H -CH=C(Cl)-P(=O)(OC~3)2 XX~.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 X~.33 Cl F -CH=C(Cl)--P(=O)(OCH3)2 X~.34 Cl H -CH=C(Cl)-P(=O)(OC2Hs~2 X~I.35 Cl Cl -CH=C(Cl)-P(=O)(OC2Hs)2 X~I.36 Cl F -CH=C(Cl)-P(=O)(OC2Hs)2 XXXI.37 Cl H -cH=c(Br)-p(=o)(ocH3)2 - ~ 0050/46586 CA 0224~6~9 1998-08-06 No. R3 R4 -Eth-P(=Yl)(Y2Rl)(Y3R2) X~I.38 Cl Cl -cH=c(Br)-p(=o)(oc~3)2 X~.39 Cl F -CH=C(13r)-P(=O)(OC~)2 XXXI.40 Cl H -cH=c(Br)-p(=o)(oc2Hs)2 X~.41 Cl Cl -CH=C(Br)-P(=O)(OC2Hs)2 X~I.42 Cl F -CH=C(Br)-P(=O)(OC2Hs)2 ~.43 Cl H -CH=C(CN)--P(=O)(OC~)2 ~.44 Cl Cl -CH=C(CN)-P(=O)(OC~)2 X~I.45 Cl F -CH=C(CN)-P(=O)(Oc~)2 X~I.46 Cl H -CH=C(CN)--P(=O)(OC2H~)2 X~.47 Cl Cl -CH=C(CN)-P(=O)(OC2H5)2 X~.48 Cl F -CH=C(CN)-P(=O)(OC2Hs)2 ( C.1.3)Preparation of the nitrobenzene derivatives XXXII:
yl ll nitration R4 ~ Eth P y2R1 3 XXXII
\=< I .
~XXlll Examples of suitable nitrating reagents are nitric acid in various concentrations, also concentrated and fuming nitric acid, mixtures of sulfuric acid and nitric acid, acetyl nitrates and alkyl nitrates.
The reaction can be carried out either in the absence of a C solvent in an excess of the nitrating reagent or in an inert solvent or diluent, suitable examples being water, mineral acids, organic acids, halohydrocarbons such as methylene chloride, anhydrides such as acetic anhydride, and mixtures of these solvents.
Starting compound XXXIII and nitrating reagent are expediently employed in approximately equimolar amounts;
however, to optimize conversion of the starting compound it may be advantageous to use the nitrating reagent in an excess of up to approximately 10 times the molar amount. If the reaction is carried out without solvent in the nitrating reagent, the latter is present in an even larger excess.
- ~ 0050/46586 CA 02245659 l998-08-06 The reaction t~mrerature is norm~lly at from (-100) to 200~C, preferably (-30) to +50~C.
Especially preferred nitro compounds of the formula XXXII
are listed in Table 4 below.
Table 4 ~2~ yl R4 ~ Eth P y2Rl XXXII
f- No. R3 R4 -E~-P(=y~)~2Rl)~3R2) ~ ~XXII.1 Cl H -cH2-cH2-p(=o)(ocH3)2 ~XXII.2 Cl Cl -CH2-CH2-P(=O)(OCH3)2 20~ .3 Cl F -CH2--CH2--P(=O)(OCH3)2 ~YXII.4 Cl H -cH2-cH2-p(=o)(oc2Hs)2 ~X~I.5 Cl Cl -CH2-CH2-P(=O)(OC2Hs)2 X~U.6 Cl F -cH2-cH2-p(=o)(oc2H5)2 25X~YU.7 Cl H --CH2--CH(Cl)-P(=O)(OCH3)2 X~YU.8 Cl Cl -CH2-CH(Cl)-P(-O)(OCH3)2 9 Cl F --CH2--CH(Cl)-P(=O)(OCH3)2 ~ L10 Cl H -cH2-cH(cl)-p(=o)(oc2Hs)2 30~YXII.11 Cl . Cl -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~U.12 Cl F -CH2-CH(Cl)-P(=O)(OC2Hs)2 U.13 Cl H -CHz-CH~Br)-P(=O)(OCH3)2 ~ .14 Cl Cl -CH2-CH ~r~p(=o)(ocH3)2 35~ .15 Cl F -CH2-CH ~r)-P(=O)(OCH3)2 X~ .16 Cl H -CH2-CH ~r)-P(=O)(OC2Hs)2 ~XXII.17 Cl Cl -cH2-cH~Br)-p(=o)(oc2Hs)2 ~XXII.18 Cl F -cH2-cH~Br)-p(=o)(oc2Hs)2 40~ .19 Cl H -CH2-CH(C ~ -P(=O)(OCH3)2 .20 Cl Cl -CH2-CH(CN~-P(=O)(OcH3)2 ~XXII.21 Cl F --CH2-CH(CN~-P(=0)(OCH3)2 , ~XXII.22 Cl H -CH2-CH(CN~-P(=O)(OC2Hs)2 45~XII.23 Cl Cl -CH2-CH(C ~-P(=O)(OC2H5)2 ~XXII.24 Cl F -CH2-CH(CN~-P(=0)(OC2Hs)2 - ~ 0050/46586 CA 02245659 lgs8-08-06 No. R3 R4 -Eth-p(=yl)(y2Rl)(y3R2) X~I.25 Cl H -CH=CH-P(=O)(OCH3)2.
X~II.26 Cl Cl -CH=CH-P(=O)(0CH3)2 X~I.27 Cl F -CH=CH-P(=0)(0CH3)2 X~II.28 Cl H -CH=CH-P(=0)(0C2H5)2 X~I.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~I.30 Cl F -CH=CH-P(=O)(OC2H5)2 X~.31 Cl H -CH=C(Cl)-P(=0)(0CH3)2 ~II.32 . Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 X~II.33 Cl F -CH=C(Cl)--P(=O)(OCH3)2 X~.34 Cl H -CH=C(Cl)--P(=O)(OC2H5)2 X~I.35 Cl Cl -CH=C(Cl)-P(=O)(OC2H5)2 X~II.36 Cl F -CH=C(Cl)-P(=0)(0C2H5)2 X~I.37 Cl H -CH=C(Br)-P(=O)(OCH3)2 X~I.38 Cl Cl -CH=C(Br)-P(=O)(OCH3)2 X~I.39 Cl F -CH=C(Br)-P(=O)(OCH3)2 X~I.40 Cl H -cH=c(Br)-p(=o)(oc2H5)2 X~I.41 Cl Cl -CH=C(Br)-P(=O)(OC2H5)2 X~II.42 Cl F -cH=c(Br)-p(=o)(oc2H5)2 X~.43 Cl H -CH=C(CN)-P(=O)(OCH3)2 ~II.44 Cl Cl -CH=C(CN)-P(=O)(OCH3)2 X~.45 Cl F --CH=C(CN)-P(=O)(OCH3)2 XX~I.46 Cl H --CH=C(CN)-P(=O)(OC2H5)2 ~I.47 Cl Cl --CH=C(CN)--P(=o)(oc2Hs)2 X~II.48 Cl F -CH=C(CN)-P(=0)(0C2H5)2 C C.1.4)Preparation of the aromatic phosphonic acid derivatives XXXIII where Eth is -CH=C(Cl)-:
yl Il (Cl-C4-alkyl)-Li R4 ~ CH0 + C13C - P Y2R3 i XXXIII
~ I XXVII
R3 y3R2 XXXIV XXVI
As regards this reaction, reference may be made to the information given above under A.13).
- 0050/46586 CA 02245659 l998-08-06 Especially preferred aromatic phosphonic acid derivatives of the for~ XXXIIIa (= XXXIII where R4 ; R4 = halogen) are listed in Table 5 below.
Table 5 yl R4~ ~ Eth - P y2Rl xxxTTTa No. R3 R4 -Eth--p(=yl)(y2Rl)(y3R2) 15X~.l Cl Cl -CH2--CH2--P(=o)(ocH3)2 x~m.2 Cl F -CH2--CH2--P(=O)(OCH3)2 f X~III.3 Cl Cl . -CH2--CH2-P(=O)(OC2Hs)2 x~m.4 Cl F --CH2--CH2--P(=O)(OC2H5)2 X~III.5 Cl Cl --CH2--CH(Cl)--P(=O)(OCH3)2 20.6 Cl F --CH2--CH(Cl)--P(=O)(OCH3)2 x~m-7 Cl Cl --CH2-CH(Cl)--P(=o)(oc2Hs)2 X~III.8 Cl F -cH2--CH(cl)-P(=O)(Oc2Hs)2 X~I.9 Cl Cl -cH2-cH(Br)-p(=o)(ocH3)2 25.10 Cl F -cH2-cH(Br)-p(=o)(ocH3)2 X~II.ll Cl Cl -CH2-CH(Br)-P(=O)(oc2Hs)2 X~III.12 Cl F -CH2--cH(Br)-p(=o)(oc2Hs)2 X~II.13 Cl Cl -CH2--CH(CN)-P(=O)(OCH3)z X~III.14 Cl F -cH2--CH(CN)--P(=O)(OCH3)2 X~.15 Cl Cl -CH2--CH(CN)-P(=O)(OC2Hs)2 C X~III.16 Cl F -CH2--CH(CN)-P(=O)(OC2Hs)2 X~III.17 Cl Cl -CH=CH-P(=O)(OCH3)2 X~m.18 Cl F -CH=CH-P(=O)(OCH3)2 X~III.l9 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~.20 Cl F --CH=CH-P(=O)(OC2Hs)2 X~II.21 Cl Cl -CH=C(Cl)--P(=O)(OCH3)2 X~III.22 Cl F -CH=C(Cl)-P(=O)(OCH3)2 X~III.23 Cl Cl -CH=C(Cl)--P(=O)(OC2Hs)2 X~II.24 Cl F --CH=C(Cl)-P(=O)(OC2Hs)2 X~II.25 Cl Cl --CH=C(Br)-P(=O)(OCH3)2 45XXXIII.26 Cl F -CH=C(Br)-P(=O)(OCH3)2 X~.27 Cl Cl -cH=c(Br)-p(=o)(oc2Hs)2 CA 02245659 l998-08-06 137 _ No. R3 R4 -Eth-P(=yl)(y2Rl)(y3R2) x~m.28 Cl F --CH=C(Br)--P(=O)(OC2Hs)2 ~II.29 Cl Cl -CH=C(CN)-P(=O)(OC~3)2 X~II.30 Cl F --CH=C(CN)-P(=O)(OC~3)2 X~II.31 Cl Cl --CH=C(CN)--P(=O)(OC2Hs)2 X~III.32 Cl F --cH=c(cN)-P(=O)(Oc2Hs)2 10 C.2) Synthesis of the thiazole ring S~ f N R50 O HN yl I R5l R4 ~ / \ ~ Eth P - y f~ ~ ~ I
- Cl/Br/I / \ \R3 Y3R2 XXXVI / \ XXXV
~ Rsl / base S N- R50 r N yl I ~ R5 = ~20 ~ 11 ~
R4~ Eth - p - y2Rl \= ~ 3 2 dehydration - XXXVII
In this process, a thiourea derivative of the formula XXXV
is reacted with a ketone of the formula XXXVI in the presence of a base, for example an alkali metal acetate, alkali metal hydrogen carbonate, ~lkAl; metal carbonate, A 1 k5~1i metal hydroxide or a tertiary amine such as triethylamine.
The process is normally carried out in an inert solvent/
diluent, e.g. in a hydrocarbon such as toluene and n-hexane, an ether such as tetrahydrofuran, or in an aprotic solvent such as dimethylfor~-m;~, acetonitrile and dimethyl sulfoxide.
CA 0224~659 1998-08-06 The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 1-50~C.
This process results in the direct formation of either the compounds of the formula I where R5 = ~20 or alcohols of the formula 2~15.X.Vll which can be dehydrated in the customary manner to give I, for example by azeotropic distillation with a suitable entraining agent, e.g. toluene or xylene, or by reaction with catalytic amounts of a strong acid such as hydrochloric acid, sulfuric acid and toluenesulfonic acid, or by esterification with a carboxylic acid chloride, sulfonic acid chloride, carboxylic anhydride or sulfonic anhydride and treatment with a base, for example an ~lk~li metal acetate, ~lk~l; metal hydrogen carbonate, Alki~l;
metal carbonate, alkali metal hydroxide or a tertiary amine f such as triethyl~m; ne and pyridine.
C.2.1)Preparation of the thiourea derivatives XXXV by reaction of isocyanates XXXVIII with ~n; 1 ;nes XXXI:
H2N yl SCN Rso ~ R4 ~ Eth - p Y2Rl ~ XXXV
~
xxxvllI \ y3R2 R
XXXI
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n- h~ne, halogenated hydlocarbons such as dichloromethane, ethers such as tetrahydrofuran, alcohols such as ethanol, aprotic solvents such as dimethylfor~- i~e, acetonitrile and dimethyl sulfoxide.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
Especially preferred thiourea derivatives of the formula XXXV are iisted in Table 6 below.
- ~ 0050/46586 CA 02245659 l998-08-06 Table 6 H
S~f N R50 HN yl R4~ Eth- F Y R
y3R2 No. R3 R4 Rso -Eth-P(=Yl)(Y2Rl)(Y3R2) X~V.l Cl H CH3 -CH2-CH2-P(=O)(OcH3)2 X~V.2 Cl Cl CH3 -CH2-CH2-P(=O)(OcH3)2 X~V.3 Cl F CH3 -CH2-CH2-P(=O)(OCH3)2 X~V.4 Cl H CH3 -CH2-CH2-P(=O)(OC2H5)2 X~V.S Cl Cl CH3 -CH2--CH2-P(=O)(OC2Hs)2 X~V.6 Cl F CH3 -CH2-CH2-P(=O)(OC2H5)2 XXXV.7 Cl H CH3 -CH2-CH(Cl)-P(=O)(OcH3)2 XX~V.8 Cl Cl CH3 -CH2-CH(Cl)--P(=O)(OCH3)2 X~V.9 Cl F CH3 -CH2-CH(Cl)-P(=O)(OCH3)2 X~V.10 Cl H CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V. 11 Cl Cl CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V.12 Cl F CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V.13 Cl H CH3 -CH2-CH(Br)-P(=O)(OCH3)2 ~V.14 Cl Cl CH3 -cH2-cH(Br)-p(=o)(ocH3)2 X~V.15 Cl F CH3 -CH2-CH(Br)-P(=O)(OCH3)2 ~- XXXV.16 Cl H CH3 -cH2-cH(Br)-p(=o)(oG2H5)2 XXXV.17 Cl Cl CH3 -CH2-CH(Br)-P(=O)(OC2Hs)2 35 X~V.18 Cl F CH3 -CH2-CH(Br)-P(=O)(Oc2Hs)2 XXXV 19 Cl H CH3 -cH2-cH(cN)-p(=o)(ocH3)2 X~V20 Cl Cl CH3 -CH2-CH(CN)-P(=O)(OCH3)2 X~V.21 Cl F CH3 -CH2-CH(CN)-P(=O)(OcH3)2 40 X~V22 Cl H CH3 -CH2--CH(CN)-P(=O)(OC2Hs)2 XXXV 23 Cl Cl CH3 -CH2-CH(CN)-P(=O)(OC2Hs)2 X~V.24 Cl F CH3 -CH2--CH(CN)-P(=O)(OC2Hs)2 X~V.25 Cl H CH3 --CH=CH--P(=O)(OC~3)2 45 X~V.26 Cl Cl . CH3 -CH=CH-P(=O)(OCH3)2 XXXV.27 Cl F CH3 -CH=CH-P(=O)(OCH3)2 - ,0050/46586 CA 022456~9 lss8-08-06 .
No. R3 R4 Rso -Eth-P(=Yl)(Y2Rl)(Y3R2) XXXV.28 Cl H CH3 -CH=CH-P(=O)(OC2Hs)2 X~V.29 Cl Cl CH3 -cH=cH-p(=o)(oc2Hs)2 5 X~V.30 Cl F CH3 -CH=CH-P(=O)(OC2Hs)2 X~V.31 Cl H CH3 --CH=C(Cl)--P(=O)(OCH3)z XXXV.32 Cl Cl CH3 -CH=C(Cl)-P(=O)(Oc~3)2 X~V.33 Cl F . CH3 -CH=C(Cl)--P(=O)(ocH3)2 lo XXXV34 Cl H CH3 --CH=C(Cl)--P(=O)(Oc2Hs) ~V.35 Cl Cl CH3 -CH=C(Cl)-P(=O)(OG2Hs) X~V.36 Cl F CH3 -CH=C(Cl)--P(=O)(Oc2Hs) X~V.37 Cl H CH3 -CH=C(Br)-P(=O)(OCH3)2 15 XXX~.38 Cl Cl CH3 -cH=c(Br)-p(=o)(ocH3)2 XX~V.39 Cl F CH3 -CH=C(13r)-P(=O)(Oc~3)2 f XXXV.40 Cl H CH3 -CH=C(13r)-P(=O)(OC2Hs) X~V.41 Cl Cl CH3 -CH=C(Br)-P(=O)(OG2Hs) 20 XXXV.42 Cl F CH3 -CH=C(Br)-P(=O)(OC2Hs) XX~V.43 Cl H CH3 -CH=C(cN)-P(=O)(OcH3) X~V.44 Cl Cl CH3 --CH=C(CN)-P(=O)(OCH3) X~V.45 Cl F CH3 -CH=C(CN)-P(=O)(OCH3) 25 XXXV.46 Cl H CH3 --CH=C(CN)--P(=O)(OC2Hs) XXXV.47 Cl Cl CH3 -CH=C(CN)-P(=O)(OC2Hs) X~V.48 Cl F CH3 --CH=C(CN)-P(=O)(OC2Hs)2 30 C.3) Synthesis of the ~h;A~olopyridazine ring NH
~, coc12 R54'~ N ~
ClCOOCCl3 ~ ~ HN yl (C13C0)2CO ~ \>
R4 ~ ~ \~ Eth P y R
XXXIX
base I ~ R5 = ~21; Z3, z4 2 N}
- ~ 0050/46586 CA 0224~6~9 1998-08-06 .
In this process, a thiosemicarbazide derivative of the formula XXXIX is reacted with phosgene, diphosgene or triphosgene in the presence of a base - for example an A 1 kA 1; metal hydrogen carbonate, ~lk~l; metal carbonate, ~lk~l; metal hydroxide or a tertiary amine such as triethyl ~m; ne or pyridine.
The process is nor~l ly carried out in an inert solvent/
diluent, e.g. in a hydrocarbon such as toluene or n-he~ne, a halogenated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran, or in an aprotic solvent such as dimethylform~m;~, acetonitrile and dimethyl sulfoxide.
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at f from 0 to 150~.
C.3.1)Preparation of the thios~m;c~bazide derivatives XXXIX by reacting hydrazines XLI with isothiocyanates XL:
\ N yl ¦ + R4 ~ Eth - P Y2Rl ~ XXXIX
NH ~
/ R3 y3R2 XLI XL
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n-heY~ne, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran, alcohols such as ethanol or aprotic solvents such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
Especially preferred thiosemicarbazide derivatives of the formula XXXIX are listed in Table 7 below.
Table 7 - . OOSO/46586 CA 02245659 1998-08-06 .
142 _ N l~ S
5HN yl R4~ Eth p_ y2Rl XXXIX ~ RS3, R54 S ~ CH2 ~4 y3R2 lOR3 No. R3 R4 --Eth-P(=Yl)(Y2Rl)(Y3R2) - X~lX.l Cl H -CH2-CH2-P(=O)(OCH3)2 15.2 Cl Cl -CH2--CH2-P(=0)(0CH3)2 X~X.3 Cl F --CHz--CH2-P(=O)(OCH3)2 X~4 Cl H --CH2-cH2--P(=o)(oc2H5)2 X~IX.5 Cl Cl --CH2-CH2--P(=O)(OC2Hs)2 20XXXIX.6 Cl F --CH2--CH2--P(=o)(oc2Hs)2 X~IX.7 Cl H -CH2-CH(Cl)--P(=O)(OC~3)2X~X.8 Cl Cl -CH2-CH(Cl)--P(=O)(0CH3)2X~X.9 Cl F -CH2--CH(Cl)-P(=O)(0CH3)225XXXIX.10 Cl H -CH2-CH(Cl)--P(=o)(oc2Hs)2 X~X.ll Cl Cl -CH2-CH(Cl)-P(=0)(0C2Hs)2X~IX.12 Cl F -cH2-cH(cl)-p(=o)(oc2H5)2X~X.13 Cl H -CH2-CH(13r)-P(=O)(OCE~3)2 30X~X.14 Cl Cl -CH2-CH(Br)-P(=O)(OC~3)2 X~IX.15 Cl F -CH2-CH(Br)-P(=O)(OCH3)2 X~X.16 Cl H -CH2-CH(Br)--P(=O)(Oc2Hs)2 X~WX.17 Cl Cl -cH2-cH(Br)-p(=o)(oc2H5)235X~x.18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2X~IX.l9 Cl H -CH2-CH(C~)--P(=O)(0CE~3)2 X~X.20 Cl Cl -CH2-CH(CN)-P(=O)(OC~)2 X~.21 Cl F -CH2-CH(CN)-P(=O)(OCH3)2 40X~X.22 Cl H -cH2-cH(cN)-p(=o)(oc2Hs)2 X~X.23 Cl Cl -CH2-CH(CN)--P(=O)(OC2Hs)2 ~X.24 Cl F --CH2--CH(CN)--P(=O)(OC2Hs)2 ~X.25 Cl H -CH=CH--P(=O)(OCH3)2 45X~X.26 Cl Cl -CH=CH--P(=O)(OCH3)2 ~WX.27 Cl F -CH=CH--P(=O)(OCH3)2 - , 0050~46586 CA02245659 1998-08-06 No. R3 R4 --Eth--P(=Yl)(Y2Rl)~y3R2) X~X.28 Cl H --CH=CH-P(=O)(OC2Hs)2 X~.29 Cl Cl -CH=CH-P(=O)(Oc2Hs)2 5X~IX.30 Cl F --CH=CH-P(=O)(OC2H5)2 X~X.3 1 Cl H --CH=C(CI)--P(=O)(OC~3)2 X~X.32 Cl Cl --CH=C(Cl)-P(=O)(OCEO2 - X~lX.33 Cl F --CH=C(Cl)-P(=O)(OCH3)2 10X~IX.34 Cl H -CH=C(CI)-P(=O)(OC2Hs)2 ~X.35 Cl Cl --CH=C(Cl)-P(=O)(OC2Hs)2 X~X.36 Cl F --CH=C(Cl)-P(=O)(OC2Hs)2 X~X.37 Cl H -CH=C(Br)-P(=O)(OCH3)2 15X~IX.38 Cl Cl -cH=c(Br)-p(=o)(oc~)2 X~IX.39 Cl F -CH=C(Br)-P(=O)(OC~)2 f X~X.40 Cl H -cH=c(Br)-p(=o)(oc2Hs)2 X~.41 Cl Cl -CH=C(13r)-P(=O)(OC2Hs)2 zo~X.42 Cl F -CH=C(Br)-P(=O)(OC2Hs)2 X~X.43 Cl H -CH=C(CN)-P(=O)(OCE~)2 X~.44 Cl Cl -CH=C(CN)--P(=O)(OCH3)2 X~IX.45 Cl F -CH=C(CN)-P(=O)(OCH3)2 25.46 Cl H --CH=C(CN)--P(=o)(oc2Hs)2 X~X.47 Cl Cl -CH=C~CN)--P(=O)(OC2Hs)2 X~.48 Cl F -CH=C(CN)--P(=o)(oc2Hs)2 30 C.3.2)Preparation of the isothiocyanates XL by reacting ~nil;nes of the form~ XXXI with thiophosgene in the presence of a base:
.' H2N yl csc12 + R4 ~ Eth p Y2Rl ~ XL
XXXI
Examples of suitable diluents/solvents are hydrocarbons such as toluene and n-hex~ne, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran, or aprotic solvents such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 Suitable bases are mainly the alkali metal acetates, ~lk~l;
metal hydrogen carbonates, A 1 k~l; metal carbonates, alkali metal hydro~;~s or tertiary amines such as triethyl~; n~
and pyridine.
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
Especially preferred isothiocyanates of the fo 1 A XL are listed in Table 8 below.
Table 8S
. C
N yl R4 ~ Eth p y2Rl XL
y3R2 No. R3 R4 -E~-P(=Y1)CY2R1)~3R2) 2S ~.1 Cl H -cH2-cH2-p(=o)(ocH3)z .2 Cl Cl -CH2-CH2-P(=0)(0cH3)2 .3 Cl F -cH2-cH2-p(=o)(ocH3)2 .4 Cl H -cH2-cH2-p(=o)(oc2Hs)2 ~-5 Cl Cl -CH2-CH2-P(=O)(0c2Hs)2 .6 Cl F -CH2-CH2-P(=0)(0C2Hs)2 ~DL.7 Cl H -CH2-CH(Cl)-P(=0)(0CH3)2 ~.8 Cl Cl -CH2-CH(Cl)-P(=0)(0CH3)2 35 ~.9 . Cl F -cH2-cH(cl)-p(=o)(ocH3)2 .10 Cl H -cH2-cH(cl)-p(=o)(oc2Hs)2 .11 Cl Cl -CH2-CH(Cl)-P~=O)(OC2Hs)2 ~.12 Cl F -cH2-cH(cl)-p(=o)(oc2Hs)2 40~.13 Cl H -CH2-CH ~r)-P(=O)(OCH3)2 .14 Cl Cl -cH2-cH~Br)-p(=o)(ocH3)2 .15 Cl F -CH2-CH~Br)-P(=O)(OCH3)2 ~.16 Cl H -CH2-CH~Br)-P(=O)~OC2Hs)2 4S~.17 Cl Cl -CH2-CH ~r)-p(=o)(oc2Hs)2 ~.18 Cl F -CH2-CH~r)-P(=0)(OC2Hs)2 - '0050/46586 CA 02245659 1998-08-06 .
No. R3 R4 -Eth-P(=Yl)CY2Rl)CY3R2) L.l9 Cl H -CH2-CH(CN~-P(=O)(OC~3)2 ~DL.20 Cl Cl --CH2-CH(CN~--P(=O)(OCH3)2 5 ~DL.21 Cl F -CH2--CH(CN~-P(=O)(OCH3)Z
L.22 Cl H -cH2-cH(cN~-p(=o)(oc2Hs)2 ~DL.23 Cl Cl -CH2-CH(CN~-P(=O)(OC2Hs)2 ~nL.24 Cl F --CH2-CH(CN~-P(=O)(OC2Hs)2 10 ~nL.25 Cl H --CH=CH--P(=O)(OCH3)2 ~DL.26 Cl Cl -CH=CH-P(=O)(OcH3)z L.27 Cl F -CH=CH-P(=O)(OcH3)2 ~L.28 Cl H -CH=CH-P(=O)(Oc2H5)2 15 ~3L.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 ~nL.30 Cl F -CH=CH-P(=O)(Oc2Hs)2 f ~DL.31 Cl H --CH=C(Cl)--P(=O)(OCH3)2 ~nL.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 20 ~DL.33 Cl F -CH=C(Cl)-P(=O)(OCH3)2 ~L.34 Cl H --CH=C(Cl)-P(=O)(OC2Hs)2 ~L.35 Cl Cl --CH=C(Cl)-P(=O)(Oc2Hs~
~DL.36 Cl F --CH=C(Cl)--P(=o)(oc2Hs)2 25 ~nL.37 Cl H -CH=C~Br)-P(=O)(OCHO2 L.38 Cl Cl -cH=c~Br)-p(=o)(oc~3)2 L.39 Cl F -cH=c~Br)-p(=o)(oc~3)2 ~L.40 Cl H -cH=c~Br)-p(=o)(oc2Hs)2 ~L.41 Cl Cl -cH=c~Br)-p(=o)(oc2Hs)2 ~DL.42 Cl F -CH=C~Br)-P(=O)(OC2Hs)2 - ~DL.43 Cl H -CH=C(CN~-P(=O)(OCH3)2~- ~DL.44 Cl Cl -CH=C(CN~-P(=O)(OCH~)2~DL 45 Cl F - CH=C(C~9-P(=O)(OCH3)2 ~DL 46 Cl H --CH=C(CN~--P(=o)(oc2Hs)2 .47 Cl Cl -CH=C(CN~-P(=O)(Oc2Hs)2 ~L.48 Cl F -CH=C(CN9-P(=O)(OC2Hs)2 ~ 0050/46586 CA 0224~659 1998-08-06 ~ - 146 ~
C.4) Synthesis of the pyrrolothiadiazole ring 5Rss NH(-HX) R55 NH2( HX) N +XL
,,NH or ~ ~
~ R56 i --~
HN yl R4 ~ Eth- 1I y2Rl oxidation 5 XLIV
X is the anion of the acid, preferably a chloride, bromide, hydrogen sulfate or 1/2 sulfate ion.
In this process, an isothiocyanate of the formula XL is reacted with an ~m; ~; ne of the fo 1~ XLII or XLIII.
he process is nor~-l ly carried out in an inert solvent/
diluent, e.g. in a h~dLocarbon such as toluene and n-he~ne, a halogenated hydrocarbon such as dichlol~...eLhane, an ether such as tetrahydrofuran, an alcohol such as ethanol, or in an aprotic solvent such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
Alternatively, XL can also be reacted with an acid addition salt of the Am; ~; ne XLII or XLIII ( for example with hydrochloric or sulfuric acid). In this case, the process is carried out in the presence of a base, for example an ~lk~l; metal acetate, ~1k~1 i metal hydrogen carbonate, 4S A 1 k~li metal carbonate, alkali metal hydroxide or a tertiary amine such as triethylamine or pyridine.
. ~ 0050/46586 CA 022456~9 1998-08-06 .
The reaction products of the formula XLIV are then oxidized in one of the solvents mentioned for the preparation of XLIV, preferably using a halogen such as chlorine or bromine.
Both the conversion of XL into XLIV and the oxidation of XLIV are generally carried out between the melting point and the boiling point of the reaction mixture in question, preferably at from 0 to 150~C.
C.5) Synthesis of the uracil ring by reacting an isocyanate of the forml~l A XLV with an aminoacrylic acid derivative oi~ the for~l~ XLVI in the presence of a strong base:
O
C
~ o_ ( Cl-C4-alkyl ~ + R4~ Eth--E~ y2Rl ~ base XLVI XLV
I ~R5 = ~1 ~
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n-heYAne~ halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran or aprotic solvents such as dimethylfor--m;~e, acetonitrile . and dimethyl sulfoxide.
-Suitable bases are mainly the alkali metal hydrides, ~1 kA 1 i metal alkoxides, A lk~l; metal amides, alkali metal hydroY~es or alkyllithium cG...~o~nds such as butyllithium.
The reaction is generaliy carried out bet-wêen the mêltirlg point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
Those process products I where R5 is ~1 and R8 is hydrogen can subsequently be alkylated or aminated in the presence of a base:
. 45 - ~ 0050/46586 CA 0224~6~9 l998-08-06 I ~ R5 ~ ~1; R8 = EI~ + Cl--C4--alkyl--La I ~ R5 ~>
baseR3 = C1-C4-alkyl ~ Cl-C4-haloalkyl-La R5 = ~l I ~ R5 = ~1; R8 _ ~ ~ I' R8 = Cl-C4_ , base haloalkyl J
I ~ R5 = ~1 ; R8 = H } ; ~ R5 = ~1 ; R8 = NH2}
La is a customary leaving group, in particular h~l;~, triflate, tosylate or mesylate;
Lb is a customary leaving group, in particular ~
hydrogen sulfate, mono- or dinitroph~oxy, i.e., for example, chloro ine~ hydroxylr ;ne-O-sulfuric acid or 2,4-dinitrophenoxyamine.
The solvents mentioned for the synthesis of the uracil ring are likewise suitable here.
Examples of useful bases are the ~lk~l; metal acetates, ~l kA 1; metal hydrogen carbonates, alkali metal carbonates and ~1 k~ 1; metal hydroxides, and tertiary ~;nes such as triethylamine and pyridine.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from O to 150~C.
C.5.1)Preparation of the isocyanates XLV by reacting ~nil;nes of the formula XXXI with phosgene, diphosgene or triphosgene in the presence of a base:
E~2N yl COCl2 ~ 1I base ClCOOCCl3 ~ + R4 ~ Eth -- p Y2R1 3 XLV
~ (C13CO)2CO y3R2 XXXI
Examples of suitable solvents~diluents are hydrocarbons such as toluene and n-hexane, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran and ~ 0050/46586 CA 0224S6~9 1998-08-06 ~ .
aprotic solvents such as dim~ethylform~m;~e, acetonitrile and dimethyl sulfoxide.
Suitable bases are mainly the A 1 kA 1; metal acetates, alkali metal hydrogen carbonates, A l kA l; metal carbonates, alkali metal hydro~;~es or tertiary Am;nes such as triethyl Am; ne and pyridine.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from O to lSO~C.
C.6) Synthesis of a cyclic imide ring by reacting an ~n;line of the formula XXXI with an anhydride of the formula XLVII or XLVIII in the presence of an acid:
R13 o acid / ; I ~ R5 = ~3; y4 = o R14 ~,~~ H2N ' yl 20 o + R4 ~ Eth p--R21 o XXXI
\Z~
2Z - Z2 o ~ I R5 = ~6 ; y5,y6 = o;
acid ~, Zl and/or Il ~ Z2 = CH
XLVIII
Examples of suitable acids are mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, carboxylic acids such as acetic acid or sulfonic acids such as benzene- and toluenesulfonic acid.
The process is no -l~y carried out in an inel~ solvel..~
diluent, for example in a hydrocarbon such as toluene or n-h~YAne, a halogenated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran, an alcohol such as ethanol, a carboxylic acid such as acetic acid, or in an aprotic solvent such as dimethylform~m;~e, acetonitrile or dimethyl sulfoxide.
- 0050/46586 CA 0224~6~9 1998-08-06 .
150 -~
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
5 Unless otherwise specified, all processes described above are ex-pediently carried out under atmospheric pressure or under the in-herent autogeneous pressure of the reaction mixture in question.
In general, the reactants are employed in a molar ratio of from 0.95:1 to 5:1.
As a rule, the reaction mixtures are worked up by methods known per se, for example by diluting the reaction solution with water followed by isolation of the product by means of filtration, 15 crystallization or solvent extraction, or by 1 ~ving the solvent, partitioning the residue in a mixture of ~ water and a suitable organic solvent and working up the organic f phase to give the product.
20 The substituted aromatic phosphonic acid derivatives I can be ob-t~;ne~ from their preparation as isomer mixtures which, however, can be separated into the pure isomers, if desired, by the methods customary for this purpose, such as crystallization or chromatography, also on an opt;cA~ly active adsorbate. Pure op-25 tically active isomers can be prepared advantageously from suit-able optically active starting materials.
Agriculturally useful salts of the cG...~ounds I can be formed by reaction with a base of the cation in question, preferably an al-30 kali metal hydroxide or alkali metal hydride, or by reaction withan acid of the anion in question, preferably of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or nitric - acid.
Salts of I whose metal ion is not an alkali metal ion can also be prepared in the customary m~nne~ by double decomposition of the alkali metal salt in question, and ammonium, phosphonium, sulfo-nium and sulfoxonium salts using ammonia, phosphonium hydroxide, 40 sulfonium hydroxide or sulfoxonium hydroxide.
The compounds I and their agriculturally useful salts, both as isomer mixtures and in the form of the pure isomers, are suitable as herbicides. The herbicidal compositions comprising I are ca-45 pable of effecting very good vegetation control on non-crop areas, especially at high rates of application. In crops such as wheat, rice, maize, soybeans and cotton, they are active against ~ 0050/46586 CA 0224~6~9 1998-08-06 .
broad-leaved weeds and grass weeds without damaging the crop plants to a substantial extent. This effect is observed especial-ly at low rates of application.
5 Depending on the application method in ~uestion, the compounds I, or the herbicidal compositions comprising them, can also be employed in a further nl~mb~ of crop plants for el ;m; n~ting unde-sirable plants. Suitable crops are for example the following:
10 Allium cepa, AnAn~ comosus, Arachis hypogaea, Asparagus offici-- nalis, Beta vulgaris spec. altissima, Beta vulgaris spec. rapa, - srassica napus var. napus, Brassica napus var. nApobrassica~
srassica rapa var. silvestris, Camellia sinensis, Carth~mlla tinc-torius, Carya ill;noinensis, Citrus limon, Citrus sinensis, Cof-15 fea arabica (Coffea canephora, Coffea liberica), Cucumis satiw s,Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgare, Humulus lupulus, Ipomoea ba-20 tatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycop-ersicon lycopersicum, Malus spec., M~n;hot esculenta, Medicago sativa, Musa spec., Nicotiana tabacum (N. rustica), Olea euro-paea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus spec., Pisum sativum, Prunus avium, Prunus persica, 25 Pyrus cn~ n; ~, ~ibes sylvestre, Ricinus c~ ni~ Saccharum officinarum, Secale cereale, Solanum tuberosum, Sorghum bicolor (S. w lgare), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera and Zea mays.
In addition, the compounds I can also be used in crops which tol-erate the action of herbicides as a result of breeding, including genetic engineering methods.
35 Moreover, the substituted aromatic phosphonic acid derivatives I
are also suitable for desiccating and/or defoliating plants.
As desiccants, they are especially suitable for desiccating the aerial parts of crop plants such as potatoes, oilseed rape, sun-40 flowers and soybeans. This allows completely mechanical harvest-ing of these important crop plants.
Also of economic interest is to facilitate harvesting, which is 45 made possible by concentrating, over a period of time, dehis-cence, or reducing the adherence to the tree, in citrus fruit, olives or other species of pomaceous fruit, stone fruit and nuts.
The same mech~n; fi~, i.e. promotion of the formation of abscission 0050/46586 CA 0224~6~9 l998-08-06 tissue between fruit or leaf and shoot of the plants, is also im-portant for readily controllable defoliation of useful plants, in particular cotton.
5 ~oreover, shortening the period within which the individual cot-ton plants mature results in an improved fiber quality after harvesting.
10 The compounds I or the compositions comprising them can be used for example in the form of directly sprayable aqueous solutions, powders, suspensions, also highly concentrated aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, materials for spreading or granules, by means or 1~ spraying, atomizing, dusting, spreading or pouring. The use forms depend on the int~n~e~ aims; in any case, they should guarantee the finest possible distribution of the active ingredients ac-f~ cording to the invention.
zo Suitable inert a~ ries are mainly: mineral oil fractions ofmedium to high boiling point, such as kerosene and diesel oil, furthermore coal tar oils and oils of vegetable or ~nim~l origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. paraffins, te-trahydronaphthalene, alkylated naphthalenes and their deriva-25 tives, alkylated benzenes and their derivatives, alcohols such asmethanol, ethanol, propanol, butanol and cycloh~x~nol, ketones such as cycloh~none, strongly polar solvents, e.g. amines, such as N-methylpyrrolidone, and water.
30 Aqueous use forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible gran-ules by adding water. To prepare emulsions, pastes or oil disper-sions, the substrates, as such or dissolved in an oil or solvent, can be homogenized in water by means of a wetting agent, tack-35 ifier, dispersant or emulsifier. Alternatively, it is possible toprepare concentrates comprising active substance, wetting agent, t~ck;fier, dispersant or emulsifier and, if desired, solvent or oil, which are suitable for dilution with water.
40 Suitable surfactants are the alkali metal salts, alkaline earth metal salts and ammonium salts of aromatic sulfonic acids, e.g.
ligno-, phenol-, naphthalene- and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- and alkylarylsulfonates, of alkyl sulfates, lauryl ethyl sulfates and fatty alcohol sulfates, 45 and the salts of sulfated hexa-, hepta- and octadecanols and of fatty alcohol glycol ethers; condensates of sulfonated naphtha-lene and its derivatives with formaldehyde, condensates of naph-0050/46586 CA 0224~6~9 1998-08-06 .
153 _ thalene or o~ the naphthalenesulfonic acids with phenol and for-maldehyde, polyoxyethylene octylp~enol ether, ethoxylated isooc-tyl-, octyl- or nonylphenol~ alkylphenyl polyglycol ether, tribu-tylphenyl polyglycol ether, alkylaryl polyether alcohols, iso-5 tridecyl alcohol, fatty alcohol/ethyleneoxide condensates,ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxy-propylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin-sulfite waste liquors or methylcellulose.
10 Powders, materials for spreading and dusts can be prepared by mixing or grinding together the active substances with a solid carrier .
15 Granules, e.g. coated granules, impregnated granules and homo-geneous granules, can be prepared by binding the active ingredi-ents to solid carriers. Solid carriers are mineral earths, such as silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loss, clay, dolomite, diatomaceous earth, cal-20 cium sulfate, magnesium sulfate, magnesium oxide, ground syn-thetic materials, fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, and products of vegetable origin, such as cereal meal, tree bark meal, wood meal and nut-shell meal, cellulose powders or other solid carriers.
The concentrations of the active ingredients I in the ready-to-use prQducts can be varied within wide ranges. In general, the formulations comprise approximately from 0.001 to 98 % by weight, preferably 0.01 to 95 % by weight, of at least one active in-30 gredient. The active ingredients are employed in a purity of from 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
,, _, ~_ The formulation examples which follow illustrate the preparation of such products:
I. 20 parts by weight of the compound No. IAh.432 are dis-solved in a mixture composed of 80 parts by weight of alky-lated benzene, 10 parts by weight of the adduct of 8 to 10 mol of ethylene oxide to 1 mol of oleic acid N-monoethano-lAmi~e, 5 parts by weight of calcium dodecylbenzenesulfo-nate and 5 parts by weight of the adduct of 40 mol of eth-ylene oxide to 1 mol of castor oil. Pouring the solution into 100,000 parts by weight of water and finely distribut-ing it therein gives an aqueous dispersion which comprises 0.02 % by weight of the active ingredient.
.
. ~ OOSO/46586 CA 022456~9 1998-08-06 .
II. 20 parts by weight of the compound No. IAh.861 are dis-solved in a mixture comrosed of 40 parts by weight of cy-cloheYAnnne, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 7 mol of ethylene oxide to 1 mol of S isooctylphenol and 10 parts by weight of the adduct of 40 mol of ethylene oxide to 1 mol of castor oil. Pouring the solution into 100,000 parts by weight of water and finely distributing it therein gives an aqueous dispersion which comprises 0.02 % by weight of the active ingredient.
III. 20 parts by weight of the active ingredient No. IBg.861 are dissolved in a mixture composed of 25 parts by weight of cyclohe~none, 65 parts by weight of a mineral oil fraction of boiling point 210 to 280~C and 10 parts by weight of the adduct of 40 mol of ethylene oxide to 1 mol of castor oil.
Pouring the solution into 100,000 parts by weight of water and finely distributing it therein gives an aqueous disper-sion which comprises 0.02 % by weight of the active ingre-dient.
IV. 20 parts by weight of the active ingredient No. ICh.860 are mixed thoroughly with 3 parts by weight of sodium diisobu-tylnaphthalene-~-sulfonate, 17 parts by weight of the so-dium salt of a lignosulfonic acid from a sulfite waste liq-uor and 60 parts by weight of pulverulent silica gel and the mixture is ground in a hA~?r mill. Finely distributing the mixture in 20,000 parts by weight of water gives a spray mixture which comprises 0.1 % by weight of the active ingredient~
V. 3 parts by weight of the active ingredient No. ICh.llS4 are mixed with 97 parts by weight of finely divided kaolin.
This gives a dust which comprises 3 ~ by weight of the active ingredient.
VI. 20 parts by weight of the active ingredient No. Ish.860 are mixed intimately with 2 parts by weight of calcium dodecylbenzenesulfonate, 8 parts by weight of fatty alcohol polyglycol ether, 2 parts by weight of sodium salt of a phenol/urea/formaldehyde condensate and 68 parts by weight of a paraffinic mineral oil. This gives a stable oily dis-persion.
45 VII. 1 part by weight of the compound No. IBh.861 is dissolved in a mixture composed of 70 parts by weight of cyclohexa-none, 20 parts by weight of ethoxylated isooctylphenol and CA 0224~6~9 l998-08-06 .
155 _ 10 parts by weight of ethoxylated castor oil. The resulting mixture can then be diluted with water to the desired con-centration of active ingredient. This gives a stable emul-sion concentrate.
s VIII. 1 part by weight of the c~ und No. IBh.1154 is dissolved in a mixture composed of 80 parts by weight of cyclohexa-none and 20 parts by weight of Wettol~ E~ 31 (= nonionic emulsifier based on ethoxylated castor oil; BASF AG). The resulting mixture can then be diluted with water to the desired concentration of active ingredient. This gives a stable emulsion concentrate.
15 The active ingredients I or the herbicidal compositions can be applied pre- or post-emergence. If the active ingredients are less well tolerated by certain crop plants, application tech-niques may be used in which the herbicidal compositions are sprayed, with the aid of the spraying apparatus, in such a way 20 that they come into as little contact, if any, with the leaves of the sensitive crop plants, while the active ingredients reach the leaves of undesirable plants which grow underneath, or the bare soil sur~ace (post-directed~ lay-by).
25 Depending on the aim of control, the season, the target plants and the growth stage, the application rates of active ingredient I are from 0.001 to 3.0, preferably 0.01 to 1.0, kg of active substance (a.s.) per ha.
30 To widen the spectrum of action and to achieve synergistic ef-fects, the substituted aromatic phosphonic acid derivatives I may be mixed with a large number of representatives of other herbici-dal or growth-regulating active ingredients and applied jointly.
Suitable examples of components in mixtures are 1,2,4-th;A~
zoles, 1,3,4- th; AA;~zoles, amides, aminophosphoric acid and its derivatives, aminotriazoles, ~n; 1; ~es, aryloxy-/hetaryloxyalka-noic acids and their derivatives, benzoic acid and its deriva-40 tives, benzoth;~A;A~inones, 2-(hetaroyl/aroyl)-1,3-cyclohexane-diones, hetaryl-aryl-ketones, benzylisoxazolidinones, meta-CF3-phenyl derivatives, carbamates, quinol;necA~boxylic acid and its derivatives, chloroacet~n;l;des, cycloh~YAne-1,3-dione de-rivatives, diazines, dichloropropionic acid and its derivatives, 45 dihydrobenzofurans, dihydrofuran-3-ones, dinitroanilines, dini-trophenols, diphenyl ethers, dipyridyls, halocarboxylic acids and their derivatives, ureas, 3-phenyluracils, imidazoles, imidazoli-nones, N-phenyl-3,4,5,6-tetrahydrophthAl;~; AeS, o~AA;Azoles, oxi-CA 022456~9 1998-08-06 .
~anes, phenols, aryloxy- and hetaryloxyphenoxypropionic esters, phenylacetic acid and its derivatives, 2-phenylpropionic acid and its derivatives, pyrazoles, phenylpyrazoles, pyridazines, pyri-dinecarboxylic acid and its derivatives, pyrimidyl ethers, sulfo-5 n~ es, sulfonylureas, triazines, triazinones, triazolinones,triazolcarbo~A~;~s and uracils.
It may furthe~more be advantageous to apply the compounds I, alone or in com~ination with other herbicides, together with 10 further crop protection agents, for example with pesticides or with agents for controlling phytopathogenic fungi or bacteria.
Also of interest is the miscibility with mineral salt solutions, which are employed for treating nutritional and trace element deficiencies. ~on-phytotoxic oils and oil concentrates may also 15 be added~
Preparation examples 20 EXample 1 Diethyl 2-(2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-py-razol-3-yl)-4-fluorophenyl)vinylphosphonate (No. IBg.861) 1 g (3 mmol) of tetraethyl methanediphosphonate was dissolved in 25 50 ml of toluene and treated with 80 mg (3.2 mmol) of sodium hy-dride. After the evolution of gas had ceased, a solution of 1 g (2.9 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoroh~nz~ldehyde in 50 ml of toluene was added.
The reaction mixture was subsequently stirred for 16 hours at 30 room temperature and then treated with 0.15 1 of water. The prod-uct of value was extracted from the aqueous phase usiny 50 ml of toluene. Finally, the combined organic phases, in turn, were washed with water and then dried over magnesium sulfate and con-centrated. Yield: 1.1 g.
Precursor 1.1 5-(4-Chloro-2-fluoro-5-methylphenyl)-1,2-dihydro-2-methyl-3H-pyrazol-3-one 34.7 g (0.75 mol) of methylhydrazine were added to a solution of 177 g (0.68 mol) of ethyl 3-(4-chloro-2-fluoro-5-methylphe-nyl)-3-o~opl~pionate in 500 ml of diethylene glycol. After 6 hours at 100~C, the mixture was poured into 4 1 of water. The so-45 lids were subsequently removed and dried. Yield: 133 g; m.p.:155-156~C.
0050/46586 CA 0224~6~9 1998-08-06 Precursor 1.2 3-(4-Chloro-2-fluoro-5-methylphenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole Gaseous chlorodifluoromethane was passed for 2 hours into a sol-ution of 133 g (0.55 mol) of 5-(4-chloro-2-fluoro-5-methylphe-nyl)-1,2-dihydro-2-methyl-3H-pyrazol-3-one and 110 g (2.7 mol~ of sodium hydroxide in 1 1 of ~;ox~ne and 0.5 1 of water at room temperature. The reaction solution was then poured into 2 1 of-water, whereupon the aqueous phase was extracted three times using ethyl acetate. The combined organic phases were dried over magnesium sulfate and then filtered and concentrated. The residue was purified by means of column chromatography on silica gel 15 (eluent: cyclohex~ne/ethyl acetate = 9:1) followed by preparative MPLC on silica gel (identical eluent). Yield: 43 g.
NMR (250 MHz; in CDCl3): ~ tppm] = 2.37 (s,3H), 3.80 (s,3H), - 6.30 (s,lH), 6.57 (t,lH), 7.14 (d,lH), 7.82 (d,lH).
20 PrecursOr 1.3 4-Chloro-3-(4-chloro-2-fluoro-5-methylphenyl)-5-difluorome-thoxy-l-methyl-lH-pyrazole 25 22 g (0.16 mol) of sulfuryl chloride were added dropwise to a solution of 43 g (0.lS mol) of 3-(4-chloro-2-fluoro-5-methylphe-nyl)-5-difluoromethoxy-1-methyl-lH-pyrazole in 250 ml of tetrach-loromethane. After the reaction solution had subsequently been stirred for 16 hours, 200 ml of saturated aqueous sodium hydloyen 30 carbonate solution was added dropwise. The organic phase was then separated off, washed using saturated sodium chloride solution, dried over magnesium sulfate, then filtered and finally concen-trated. Yield: 46 g.
lH NMR (250 MHz; in CDCl3): ~ [ppm] = 2.37 (s,3H), 3.84 (s,3H), 35 6.71 (t,lH), 7.21 (d,lH), 7.40 (d,lH).
Precursor 1.4 4-Chloro-3-(4-chloro-5-diLLI ~thyl-2-fluorophenyl)-5-difluo-romethoxy-1-methyl-lH-pyrazole A solution of 46 g (0.14 mol) of 4-chloro-3-(4-chloro-2-fluoro-5-methylphenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole and 62.9 g (0.35 mol) of N-bromosuccin;mi~e in 2 1 of tetrachloromethane was 45 irradiated for 3.5 hours with a 1500 watt high-pressure mercury OOS0/46586 CA 0224~6~9 1998-08-06 .
lamp and a W lamp. The solids content was subsequently filtered off and washed two more times using tetrachloromethane. The com-bined filtrates were then concentrated. Yield: 68 g.
lH NMR (270 MHz; in CDCl3): a tppm] = 3.86 (s,3H), 6.72 (t,lH), 5 7.05 (s,lH), 7.19 (d,lH), 8.23 (d,lH).
Precursor 1.5 2-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyra-lO zol-3-yl)-4-fluorobenzaldehyde 68 g (0.14 mol) of 4-chloro-3-(4-chloro-5-dibLom~llethyl-2-fluoro-phenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole were dissolved in 200 ml of concentrated sulfuric acid, with ice-cooling, whereupon 15 the mixture was heated at 100~C until the evolution of gas had ceased. It was then poured into 4 1 of ice-water. The mixture was f-- subsequently extracted three times using ethyl acetate. The com-bined organic phases were washed with water, then dried over mag-nesium sulfate and finally concentrated. The crude product was 20 purified by means of silica gel column chromatography (eluent:
h~Ane/ethyl acetate = 8:1). Yield: 35 g; m.p.: 95-98 ~C.
Example 2 Diethyl l-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No.
IBh.861) 2 ml of a butyllithium solution (1.6 M in he~ne; 3.Z mmol) were 30 added in such a way to a solution, cooled at (-70)~C, of 1.63 g (6.4 mmol) of diethyl trichloromethanephosphonate in 20 ml of te-trahydrofuran that the temperature did not exceed (-65)~C. Stir-ring was subsequently continued for 1 hour at from (-65) to (-70)~C, whereupon a solution of 1 g (2.9 mmol) of 2-chlo-35 ro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorobenzaldehyde in 20 ml of tetrahydrofuran was slowly added dropwise. Stirring was continued for 30 minutes, the cooling bath was then le -~ed, and stirring was continued for a further 16 hours, during which process the temperature of the mixture 40 climbed to approximately 20~C. After 5 g of ammonium chloride had been added, the reaction mixture was poured into 50 ml of water.
The product of value was then obt~; neA from the aqueous phase by extracting it twice using in each case 50 ml of methyl tert-butyl ether. The combined organic phases were washed using saturated 45 aqueous sodium chloride solution and water, dried over magnesium sulfate and finally concentrated. The crude product was purified - , 0050/46586 CA 0224~6~9 1998-08-06 .
by means of silica gel column chromatography (eluent: he~Ane!
ethyl acetate = 4:1). Yield: 0.7 g.
Example 3 Diethyl 2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-(lH,3H)-pyr;miA;ne~;on-3-yl)phenyl]vinylphosphonate (No. IAg.861) 0.12 g (4.7 mmol) of sodium hydride was added to a solution of 10 1.5 g (5.2 mmol) of tetraethyl methanediphosphonate in 50 ml of toluene. After the evolution of gas had ceased, a solution of 1.5 g (4.3 mmol) of 2-chloro-4-fluoro-S-(l-methyl-6-trifluorome-thyl-2,4(1H,3H)-pyr;m;~;ne~;on-3-yl)benzaldehyde in 50 ml of to-luene was added. The mixture was subsequently stirred for a 15 further 16 hours at approximately 20~C. For working-up, the reac-tion mixture was treated with 0.15 1 of water. Residues of the ~- product of value which had r~m~; ne~ in the aqueous phase were ex-tracted using 50 ml of toluene. The combined organic phases were subsequently washed with water, dried over magnesium sulfate and 20 finally concentrated. Yield: 1.4 g.
Precursor 3.1 2-Chloro-4-fluoro-5-isocyanatohen7aldehyde (O-methyl)oxime 411.3 g of diphosgene (2.08 mol) were added dropwise to a sol-ution of 383 g (1.89 mol) of 5-amino-2-chloro-4-fluorobenz-aldehyde (O-methyl)oxime in 2 1 of toluene. The temperature was then slowly raised to 110 ~C in the course of approximately 30 6 hours so that the evolution of gas proceeded in a controlled ~nn~r, The mixture was subsequently refluxed for a further 5 hours. The reaction mixture was then left to cool and finally concentrated. Yield: 432 g.
The product was processed without purification.
Precursor 3.2 2-Chloro-4-fluoro-5-(6-trifluoromethyl-2,4(1H,3H)-pyr; ;~;ne-dion-3-yl)benzaldehyde (O-methyl)oxime A solution of 168.5 g (0.92 mol) of ethyl 3-amino-4,4,4-trifluo-rocrotonate in 0.1 1 of dimethylformAm;~e was added dropwise with ice-cooling to 30.4 g (1.01 mol) of 80 % by weight sodium hydride in 0.5 1 of dimethylform-m; Ae . After one hour at this tempera-45 ture, the mixture was cooled to (-30) to (-35)~C, and a solution of 210.3 g (0.92 mol) of 2-chloro-4-fluoro-5-isocyanatobenz-aldehyde (O-methyl)oxime in 0.15 1 of tetrahydrofuran was added dropwise. The reaction mixture was then stirred for 20 hours at ~ 0050/46586 CA 0224~6~9 l998-08-06 - - 160 ~
approximately 20~C, and 1.5 1 of water were subsequently added with ice-cooling. Undissolved matter in the mixture formed was removed and washed using 300 ml of water. The combined filtrates were acidified using dilute hydrochloric acid. The product of 5 value was then extracted from the solution obtained using dichlo-romethane. The extract was washed with water, dried over sodium sulfate and finally concentrated. Yield: 289 g; m.p.: 176-177~C
(diisG~lopyl ether/petroleum ether).
10 Precursor 3.3 2-Chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyri-midinedion-3-yl)benzaldehyde (O-methyl)oxime 15 First, 117.1 g (0.85 mol) of potassium carbonate were added to a solution of 281.6 g (0.77 mol) of 2-chloro-4-fluoro-5-(6-trifluo-romethyl-2,4(lH,3H)-pyrimidinedion-3-yl) hen 7~1 ~hyde (O-methyl)oxime in 0.8 1 of dimethylfor~ e, whereupon a solution of 120.2 g of methyl iodide (0.85 mol) in 0.1 l of dimethylforma-20 mide was added dropwise in the course of 1 hour. The reactionmixture was subsequently stirred for 20 hours at approximately 20~C, and 0.9 l of water was subsequently added dropwise with ice-cooling. The product of value was extracted from the resulting solution using 1 l of dichloromethane. The extract was washed 25 three times using 300 ml of water, dried over sodium sulfate and finally concentrated. Yield: 241 g; m.p.: 141-142~C (diisopropyl ether).
Precursor 3.4 30 2-Chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyri-mi~; ne~; on-3-yl)benzaldehyde 150 ml of a 30 % by weight aqueous formaldehyde solution and 150 35 ml of concentrated hydrochloric acid were added dropwise to a solution of 189.9 g (0.50 mol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimi~; ne~; on-3-yl)benzalde-hyde (O-methyl)oxime in 0.75 l of glacial acetic acid. The mix-ture was subsequently refluxed for two hours. After cooling, 0.75 40 l of water were added, whereupon the solid product of value formed was separated off and washed first with water until the reaction was neutral and then with petroleum ether. Yield: 140 g;
m.p.: 175-178~C.
. ~ 0050/46586 CA 0224~6~9 1998-08-06 .
Example 4 Diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluorome-thyl-2,4(1H,3H)-pyrimi~ine~;on-3-yl)phenyl~vinylphosphonate (No.
IAh.861) 3.2 ml of a butyllithium solution (1.5 M in hexane; 4.8 mmol) were added in such a way to a solution, cooled at (-70)~C, of 2.4 g (9.5 mmol) of diethyl trichloromethane phosphonate in 30 ml of 10 tetrahydrofuran that the temre~ature did not exceed (-65)~C. The mixture was then stirred for 1 hour at from (-65) to (-70)~C, whereupon a solution of 1.5 g (4.3 mmol) of 2-chloro-4-fluoro-5--(1--methyl-6--trifluoromethyl-2,4(1H,3H)--pyr;~;tl;ne~;on--3--yl)ben-zaldehyde in 20 ml of tetrahydrofuran was slowly added dropwise.
15 30 minutes later, the cooling bath was ~ ~-ved, and the mixture was allowed to come to room te~r~rature in the course of 16 hours. After 3.6 g of ammonium chloride had been added, the reac-tion mixture was poured into 20 ml of water. The product was ex-tracted twice from the aqueous phase using in each case 50 ml of 20 methyl tert-butyl ether. The combined organic phases were washed using saturated aqueous sodium chloride solution and water, dried over magnesium sulfate and finally concentrated. The crude prod-uct was purified by means of silica gel column chromatography (eluent: hexane/ethyl acetate - 4:1). Yield: 0.7 g.
Example 5 Dimethyl l-chloro-2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)ethylphosphonate (No. IEb.2) 30 2.8 g (10 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)~n;line were added to a solution of 31.2 g (0.23 mol) of dimethyl vinylphosphonate, 1.6 g (12 mmol) of copper(II) ~_ chloride and 1.6 g ~16 mmol) of tert-butyl nitrite in 200 ml of acetonitrile. After the reaction mixture had been stirred for 2 35 hours, 200 ml of methyl tert-butyl ether were added. The organic phase was subsequently washed twice using in each case 50 ml of water and then dried over magnesium sulfate and finally concen-trated. The crude product was purified by means of silica gel column chromatography (eluent: first cycloh~n~/methyl tert-gO butyl ether = 4:1, then ethyl acetate). Yield: 2.0 g.
.
CA 0224~6~9 1998-08-06 Example 6 Dimethyl l-chloro-2-(2-chloro-5-(5-chloro-1-difluoromethyl-2-methyl-lH-;~;~zol-4-yl)phenyl)ethylphosphonate (No. IHb.2) A solution of 42.5 g (0.26 mol) of dimethyl vinylphosphonate, 2.5 g of copper(II) chloride (19 mmol) and 1.7 g (17 mmol) of tert-butyl nitrite in 100 ml of acetonitrile was stirred for 30 min-ute~, and a solution of 3.8 g (13 mmol) of 2-chloro-5-(5-chloro-10 1-difluoromethyl-2-methyl-lH-imidazol-4-yl)~n;l;ne in 20 ml of acetonitrile was subsequently added. After 1 further hour, the mixture was concentrated, and the residue was then treated with 50 ml of water. The product was extracted from the aqueous phase using 50 ml of ethyl acetate. The organic phase was dried over 15 magnesium sulfate, filtered and finally concentrated. The crude product was purified by means of silica gel column chromatography (eluent: h~x~n~/ethyl acetate 2 4:1). Yield: 0.8 g.
Precursor 6.1 20 4(5)-(4-chlorophenyl)-2-methyl-lH-;m;~7ole 28.6 g (0.65 mol) of acetaldehyde were added dropwise with cool-ing to 320 ml of 25 % by weight aqueous ammonia solution. Then, 86.3 g (0.43 mol) of copper(II) acetate monohydrate and a sol-25 ution of 46 g (0.22 mol) of 1-(4-chlorophenyl)ethanon-2-yl acet-ate in 300 ml of dimethylform~m;de were added successively, whereupon the mixture was heated at 100~C for 30 minutes. The re-action mixture was subsequently poured into 3 1 of ice-water. The solids were filtered off and then taken up in 300 ml of ethanol.
30 Hydrogen sulfide gas was then pa~sed into this solution until sa-turation was reAche~, during which process black copper sulfide precipitated. After 5 g of active charcoal had been added, the mixture was stirred for a further 2 hours at reflux temperature, then cooled and filtered, and the filtrate was concentrated.
35 Yield: 31.5 g-1H NMR (270 MHz; in CDCl3): ~ tppm] = 2.41 (s,3H), 7.17 (s,2H),7.30 (d,2H), 7.61 (d,2H).
40 Precursor 6.2 4-(4-Chlorophenyl)-1-difluoromethyl-2-methyl-lH-imidazole 45.2 g (0.33 mol) of potassium carbonate were added to a solution of 31.5 g (0.16 mol) of 4(5)-(4-chlorophenyl)-2-methyl-lH-imida-45 zole in 150 ml of dimethylformamide. The mixture was then heatedat 90~C and chlorodifluoromethane gas was passed in for 2 hours.
The reaction mixture was subsequently poured into 300 ml of - 0050/46586 CA 022456~9 1998-08-06 .
water. The product was extracted three times from the aqueous phase using in each case 300 ml of ethyl acetate, whereupon the combined organic phases were washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate 5 and finally concentrated. Yield: 36 g.
lH NMR (270 MHz; in CDCl3): ~ lppml = 2.56 (s,3H), 7.04 (t,lH), 7.35 (m,3H), 7.68 (d,2H).
10 Precursor 6.3 5-Chloro-4-(4-chlorophenyl)-1-difluoromethyl-2-methyl-lH-Lmida-zole 26.7 g (0.19 mol) of sulfuryl chloride were added dropwise with 15 ice-cooling to a suspension of 24 g (98 mmol) of 4-(4-chlorophe-nyl)-l-difluoromethyl-2-methyl-lH-;m;~ole in 200 ml of tetrach-loromethane. After the reaction mixture had been stirred for 2 hours, an excess of saturated aqueous sodium hydrogen carbonate solution was added dropwise (still with ice-cooling). The solids 20 were subsequently filtered off. The organic phase was washed with water until neutral, dried over magnesium sulfate and concen-trated. The crude product was purified by means of silica gel column chromatography (eluent: hexA~e/ethyl acetate = 8:1).
Yield: 7.4 g.
25 lH NMR (270 MHz; in CDCl3): ~ tppm] ~ 2.60 (s,3H), 7.14 (t,lH), 7.38 (d,2H), 7.84 (d,2H).
Precursor 6.4 30 5-Chloro-4-(4-chloro-3-nitrophenyl)-1-difluoromethyl-2-methyl-lH-imidazole , . . .
- Cl-C4-alkylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, l-methylethylsulfinyl, n-butylsulfinyl, l-methylpropylsulfi-nyl, 2-methylpropylsulfinyl or l,l-dimethylethylsulfinyl, preferably methylsulfinyl, for example methylsulfinylmethyl or 2-methylsulfinylethyl;
45 - Cl-C4-haloalkylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl as men-tioned above which has attached to it a Cl-C4-alkylsulfinyl group which is partially or fully substituted by fluorine, ~ 0050/46586 CA 0224~6~9 1998-08-06 chlorine and/or bromine, e.g. difluoromethylsulfinyl, tri-fluoromethylsulfinyl, chlorodifluoromethylsulfinyl, bromodi-fluoromethylsulfinyl, 2-fluoroethylsulfinyl, 2-chloroethyl-sulfinyl, 2-bromoethylsulfinyl, 2-iodoethylsulfinyl, 2,2-di-fluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl, 2,2,2-trichloroethylsulfinyl, 2-chloro-2-fluoroethylsulfinyl, 2-chloro-2,2-difluoroethylsulfinyl, 2,2-dichloro-2-fluoro-ethylsulfinyl, pentafluoroethylsulfinyl, 2-fluoropropylsulfi-nyl, 3-fluoropropylsulfinyl, 2-chloropropylsulfinyl, 3-chlo-ropropylsulfinyl, 2-bromopropylsulfinyl, 3-bromopropylsulfi-nyl, 2,2-difluolopLopylsulfinyl, 2,3-difluoropropylsulfinyl, 2,3-dichloropropylsulfinyl, 3,3,3-trifluoropropylsulfinyl, 3,3,3-trichloropropylsulfinyl, 2,2,3,3,3-pentafluoropropyl-sulfinyl, heptafluoro~lopylsulfinyl, l-(fluoromethyl)-2-fluo-roethylsulfinyl, 1-(chloromethyl)-2-chloroethylsulfinyl, - 1-(bl~"lor"eLhyl)-2-bromoethylsulfinyl, 4-fluorobutylsulfinyl, 4-chlorobutylsulfinyl or 4-bromobutylsulfinyl, for example difluoromethylsulfinylmethyl;
20 _ Cl-C4-alkylsulfonyl is: S02-CH3, S02-C2H5, n-propylsulfonyl, S02-CH(CH3)2, n-butylsulfonyl, l-methylpropylsulfonyl, 2-methylpropylsulfonyl or S02-C(CH3), in particular S02-CH3 or S02-C2H5;
- C1-C4-alkylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by Cl-C4-alkylsulfonyl as mentioned above, preferably methylsulfonyl, for example methylsulfonylmethyl or 2-methyl-sulfonylethyl;
- Cl-C4-haloalkylsulfohyl-Cl-C4-alkyl is: Cl-C4-alkyl as men-'- tioned above which has attached to it a Cl-C4-alkylsulfonyl ' group which is partially or fully substituted by fluorine, chlorine and/or bromine, e.g. difluoromethylsulfonyl, tri-fluoromethylsulfonyl, chlorodifluoromethylsulfonyl, bl~
fluoromethylsulfonyl, 2-fluoroethylsulfonyl, 2-chloroethyl-sulfonyl, 2-bromoethylsulfonyl, 2-iodoethylsulfonyl, 2,2-di-fluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, 2,2,2-trichloroethylsulfonyl, 2-chloro-2-fluoroethylsulfonyl, 2-chloro-2,2-difluoroethylsulfonyl, 2,2-dichloro-2-fluoro-ethylsulfonyl, pentafluoroethylsulfonyl, 2-fluoropropylsulfo-nyl, 3-fluoropropylsulfonyl, 2-chloropropylsulfonyl, 3-chlo-ropropylsulfonyl, 2-bromopropylsulfonyl, 3-bromopropylsulfo-nyl, 2,2-difluoropropylsulfonyl, 2,3-difluoropropylsulfonyl, 2,3-dichloropropylsulfonyl, 3,3,3-trifluoropropylsulfonyl, 3,3,3-trichloropropylsulfonyl, 2,2,3,3,3-pentafluoropropyl-sulfonyl, heptafluoropropylsulfonyl, l-(fluoromethyl)-2-fluo-0050/46586 CA 0224~6~9 l998-08-06 ~ . .
. 20 ~-roethylsulfonyl, l-(chloromethyl)-2-chloroethylsulfonyl, l-(b~ -Lhyl)-2-bromoethylsulfonyl, 4-fluorobutylsulfonyl, 4-chlorobutylsulfonyl or 4-bromobutylsulfonyl, for example 2-chloroethylsulfonyl;
- C3-C6-alkenyl is: e.g. prop-2-en-1-yl, n-buten-4-yl, l-methyl-prop-2-en-1-yl, 2-methylprop-2-en-1-yl, 2-buten-1-yl, n-penten-3-yl, n-penten-4-yl, 1-methylbut-2-en-1-yl, 2-me-thylbut-2-en-1-yl, 3-methylbut-2-en-l-yl, l-methyl-but-3-en-1-yl, 2-methylbut-3-en-1-yl, 3-methylbut-3-en-1-yl, 1,1-dimethylprop-2-en-l-yl, 1,2-dimethylprop-2-en-1-yl, 1-ethylprop-2-en-1-yl, n-hex-3-en-1-yl, n-hex-4-en-l-yl, n-hex-5-en-1-yl, 1-methylpent-3-en-1-yl, 2-methyl-pent-3-en-1-yl, 3-methylpent-3-en-1-yl, 4-methyl-pent-3-en-1-yl, 1-methylpent-4-en-1-yl, 2-methyl-~ pent-4-en-1-yl, 3-methylpent-4-en-1-yl, 4-methyl-'- pent-4-en-1-yl, 1,1-dimethylbut-2-en-1-yl, l,l-dimethyl-but-3-en-1-yl, 1,2-dimethylbut-2-en-1-yl, 1,2-dimethyl-but-3-en-l-yl, 1,3-dimethylbut-2-en-l-yl, 1,3-dimethyl-but-3-en-l-yl, 2,2-dimethylbut-3-en-1-yl, 2,3-dimethyl-but-2-en-1-yl, 2,3-dimethylbut-3-en-1-yl, 3,3-dimethyl-but-2-en-1-yl, 1-ethylbut-2-en-1-yl, 1-ethylbut-3-en-1-yl, 2-ethylbut-2-en-1-yl, 2-ethylbut-3-en-1-yl, 1,1,2-trimethyl-prop-2-en-l-yl, 1-ethyl-1-methylprop-2-en-l-yl or 1-ethyl-2-methylprop-2-en-1-yl, in particular prop-2-en-l-yl or n-buten-4-yl;
- C3-C6-haloalkenyl is: C3-C6-alkenyl as mentioned above which is partially or fully substituted by ~luorine, chlorine and/
or bromine, e.g. 2-chloroallyl, 3-chloroallyl, 2,3-dichlo-f_~ roallyl, 3,3-dichloroallyl, 2,3,3-trichloroallyl, 2,3-dichlo-robut-2-enyl, 2-bromoallyl, 3-bl~ ~allyl, 2,3-dibl~ ~allyl, 3,3-dibromoallyl, 2,3,3-tribromoallyl or 2,3-dibromo-but-2-enyl, in particular 2-chloroallyl or 3,3-dichloroallyl;
- cyano-C3-C6-alkenyl is: e.g. 3-cyanoallyl, 4-cyanobut-2-enyl, 4-cyanobut-3-enyl or 5-cyanopent-4-enyl, preferably 3-cya-noallyl or 4-cyanobut-2-enyl, in particular 3-cyanoallyl;
- C3-C4-alkenyloxy-C1-C4-alkyl is: C1-C4-alkyl which is substi-tuted by C3-C4-alkenyloxy, such as prop-2-enyloxy, n-but-2-enyloxy, n-but-3-enyloxy, 1-methylprop-2-enyloxy or 2-methylprop-2-enyloxy, preferably allyloxy, 2-methyl-. 45 prop-2-en-1-yloxy, but-1-en-3-yloxy, but-1-en-4-yloxy or 0050/46586 CA 0224~6~9 l998-08-06 .
but-2-en-1-yloxy, for example allyloxymethyl, 2-allyloxyethyl or but-l-en-4-ylo~y -Lhyl;
- C3-C4-alkenylthio-Cl-C4-alkyl is: Cl-C4-alkyl which is sub-stituted by C3-C4-alkenylthio, such as prop-2-enylthio, n-but-2-enylthio, n-but-3-enylthio, 1-methylprop-2-enylthio or 2-methylprop-2-enylthio, preferably allylthio, 2-methyl-prop-2-en-1-ylthio, but-1-en-3-ylthio, but-1-en-4-ylthio or but-2-en-1-ylthio, for example allylthiomethyl, 2-allylthio-ethyl or but-1-en-4-ylthiomethyl;
- C3-C4-alkenylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkenylsulfinyl, such as prop-2-enyl-sulfinyl, n-but-2-enylsulfinyl, n-but-3-enylsulfinyl, l-me-thylprop-2-enylsulfinyl or 2-methylprop-2-enylsulfinyl, pre-ferably allylsulfinyl, 2-methylprop-2-en-1-ylsulfinyl, but-l-en-3-ylsulfinyl, but-1-en-4-ylsulfinyl or but-2-en-1-ylsulfinyl, for example allylsulfinylmethyl, 2-allylsulfinylethyl or but-1-en-4-ylsulfinylmethyl;
- C3-C4-alkenylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkenylsulfonyl, such as prop-2-enylsul-fonyl, n-but-2-enylsulfonyl, n-but-3-enylsulfonyl, 1-methyl-prop-2-enylsulfonyl or 2-methylprop-2-enylsulfonyl, prefera-bly allylsulfonyl, 2-methylprop-2-en-1-ylsulfonyl, but-1-en-3-ylsulfonyl, but-1-en-4-ylsulfonyl or but-2-en-1-ylsulfonyl, for example allylsulfonylmethyl, 2-allylsulfonylethyl or but-1-en-4-ylsulfonylmethyl;
- C3-C6-alkynyl is: e.g. propargyl, n-but-1-yn-3-yl, n-f but-l-yn-4-yl, n-but-2-yn-1-yl, n-pent-1-yn-3-yl, n-pent-l-yn-4-yl, n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl, 3-methylbut-l-yn-3-yl, 3-methylbut-1-yn-4-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5-yl, n-hex-1-yn-6-yl, n-hex-2-yn-l-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2-yn-6-yl, n-hex-3-yn-1-yl, n-hex-3-yn-2-yl, 3-methylpent-1-yn-3-yl, 3-methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl, 4-methyl-pent-2-yn-4-yl or 4-methylpent-2-yn-5-yl, in particular propargyl;
- C3-C6-haloalkynyl is: C3-C6-alkynyl as mentioned above which is partially or fully substituted by fluorine, chlorine and/
or bromine, e.g. 1,1-difluoroprop-2-yn-1-yl, 4-fluoro-but-2-yn-1-yl, 4-chlorobut-2-yn-1-yl, l,l-difluoro-0050~46586 CA 0224~6~9 1998-08-06 .
. .
but-2-yn-1-yl, 5-fluoropent-3-yn-1-yl or 6-fluoro-~ hex-4-yn-1-yl;
- cyano-C3-C6-alkynyl is: e.g. 3-cyanopropargyl;
S
- C3-C4-alkynyloxy-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by C3-C4-alkynyloxy, such as prop-2-ynyloxy, n-but-2-ynyloxy, n-but-3-ynyloxy or 1-methylprop-2-ynyloxy, preferably propargyloxy, but-1-yn-3-yloxy, but-1-yn-4-yloxy or but-2-yn-1-yloxy, for example propargyloxymethyl or 2-propargyloxyethyl;
- C3-C4-alkynylthio-Cl-C4-alkyl is: Cl-C4-alkyl which is substi-tuted by C3-C4-alkynylthio, such as prop-2-ynylthio, n-but-2-ynylthio, n-but-3-ynylthio or 1-methylprop-2-ynylthio, preferably propargylthio, but-1-yn-3-ylthio, but-1-yn-4-yl-thio or but-2-yn-1-ylthio, for example propargylth;o~?thyl or 2-propargylthioethyl;
- C3-C4-alkynylsulfinyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkynylsulfinyl, such as prop-2-ynyl-sulfinyl, n-but-2-ynylsulfinyl, n-but-3-ynylsulfinyl and 1-methylprop-2-ynylsulfinyl, preferably propargylsulfinyl, but-1-yn-3-ylsulfinyl, but-1-yn-4-ylsulfinyl or but-2-yn-1-ylsulfinyl, for example propargylsulfinylmethyl or 2-propargylsulfinylethyl;
- C3-C4-alkynylsulfonyl-Cl-C4-alkyl is: Cl-C4-alkyl which is substituted by C3-C4-alkynylsulfonyl, such as prop-2-ynylsul-fonyl, n-but-2-ynylsulfonyl, n-but-3-ynylsulfonyl and 1-me-f. thylprop-2-ynylsulfonyl, preferably propargylsulfonyl, but-1-yn-3-ylsulfonyl, but-1-yn-4-ylsulfonyl or but-2-yn-1-ylsulfonyl, for example propargylsulfonylmethyl or 2-propargylsulfonylethyl;
- C3-C6-cycloalkyl is: cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in particular cyclopentyl or cyclohexyl;
- C3-C8-cycloalkyl is: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, in particular cyclo-pentyl or cyclohexyl;
45 - C3-C8-cycloalkyl-Cl-C4-alkyl is: cyclopropylmethyl, cyclobu-tylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclohep-tylmethyl, cyclooctylmethyl, 1-(cyclopropyl)ethyl, 0050/46586 CA 022456~9 1998-08-06 ~ , .
1-(cyclobutyl)ethyl, 1-(cyclopentyl)ethyl, 1-(cyclohex-yl)ethyl, 1-(cycloheptyl)ethyl, 1-(cyclooctyl)ethyl, 2-(cyclopropyl)ethyl, 2-(cyclobutyl)ethyl~ 2-(cyclopen-tyl)ethyl, 2-(cyclohexyl)ethyl, 2-(cycloheptyl)ethyl, 2-(cyclooctyl)ethyl, 3-(cyclopropyl)propyl, 3-(cyclobu-tyl)propyl, 3-(cyclopentyl)propyl, 3-(cyclohexyl)propyl, 3-(cycloheptyl)propyl, 3-(cyclooctyl)propyl, 4-(cyclopro-pyl)butyl, 4-(cyclobutyl)butyl, 4-(cyclopentyl)butyl, 4-(cyclohexyl)butyl, 4-(cycloheptyl)butyl or 4-(cyclooc-tyl)butyl, in particular cyclopentylmethyl or cyclohexylme_thyl;
- C3-C8-cycloalkoxy-Cl-C4-alkyl is: cyclopropyloxymethyl, cyclobutyloxymethyl, cyclopentyloxymethyl, cyclohexyloxyme-thyl, cycloheptyloxymethyl, cyclooctyloxymethyl, 1-(cyclo-- propyloxy)ethyl, 1-(cyclobutyloxy)ethyl, 1-(cyclopentyl-'~ oxy)ethyl, 1-(cyclohexyloxy)ethyl, 1-(cycloheptyloxy)ethyl, 1-(cyclooctyloxy)ethyl, 2-(cyclopropyloxy)ethyl, 2-(cyclobu-tyloxy)ethyl, 2-(cyclopentyloxy)ethyl, 2-(cyclohexyl-oxy)ethyl, 2-(cycloheptyloxy)ethyl, 2-(cyclooctyloxy)ethyl, 3-(cyclopropyloxy)propyl, 3-(cyclobutyloxy)propyl, 3-(cyclo-pentyloxy)propyl, 3-(cyclohexyloxy)propyl, 3-(cycloheptyl-oxy)propyl, 3-(cyclooctyloxy)propyl, 4-(cyclopropyloxy)butyl, 4-(cyclobutyloxy)butyl, 4-(cyclopentyloxy)butyl, 4-(cyclo-hexyloxy)butyl, 4-(cycloheptyloxy)butyl or 4-(cycloocty-loxy)butyl, in particular cyclopentyloxy-..aLhyl, cyclohexy-loxymethyl or 2-(cyclopentyloxy)ethyl.
30 3- to 7-membered heterocyclyl is to be understood as ~A~;ng not only saturated or partially or fully unsaturated but also aro-matic heterocycles having one to three hetero atoms selected from a group consisting of - one to three nitrogen atoms, 35 - one or two oxygen and - one or two sulfur atoms.
Examples of saturated heterocycles which can contain a carbonyl or thiocarbonyl ring member are:
40 oxiranyl, thiiranyl, aziridin-1-yl, aziridin-2-yl, diaziri-din-l-yl, diaziridin-3-yl, oxetan-2-yl, oxetan-3-yl, thie-tan-2-yl, thietan-3-yl, azetidin-l-yl, azetidin-2-yl, azeti-din-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydro-thiophen-2-yl, tetrahydrothiophen-3-yl, pyrrolidin-l-yl, pyrroli-45 din-2-yl, pyrrolidin-3-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-yl, 1,3-oxathiolan-4-yl, 1,3-oxathiolan-5-yl, 1,3-oxazolidin-2-yl, 1,3-oxazolidin-3-yl, 1,3-oxazolidin-4-yl, ~ OOSO/46586 CA 0224~6~9 l998-08-06 ~ . , .
1,3-oxazolidin-5-yl, 1,2-oxazolidin-2-yl, 1,2-oxazolidin-3-yl, 1,2-oxazolidin-4-yl, 1,2-oxazolidin-5-yl, 1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrroli-din-5-yl, tetrahydropyrazol-l-yl, tetrahydropyrazol-3-yl, te-5 trahydlo~ylazol-4-yl~ tetrahydlo~ylan-2-yl, tetrahydlo~ylan-3 tetrahyd~u~yLan-4-yl~ tetrahydrothiopyran-2-yl, tetrahydloLhi ran-3-yl, tetrahydropyran-4-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1,3-dioxan-2-yl, 1,3-~;ox~n-4-yl, 1,3-dioxan-5-yl, 1,4-~; OxA n-2-yl, 1,3-oxathian-2-yl, 1,3-oxa-lO thian-4-yl, 1,3-oxathian-5-yl, 1,3-oxathian-6-yl, 1,4-oxa-thian-2-yl, 1,4-oxathian-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, hexahyaropyr;~Az;n-l-yl, hexahydropyr;~A~in-3-yl, hexahydropyr; ~A 7; n-4-yl, hexahydlu~yr;~;~in-l-yl~ hexahydropy-rimidin-2-yl, hexahydLo~ ;n-4-yl, hexahydropyrim;~;n-5-yl, 15 piperazin-l-yl, piperazin-2-yl, piperazin-3-yl, hexahy-dro-1,3,5-triazin-1-yl, hexahydro-1,3,5-triazin-2-yl, oxe-. pan-2-yl, oxepan-3-yl, oxepan-4-yl, thiepan-2-yl, thiepan-3-yl, thiepan-4-yl, 1,3-dioxepan-2-yl, 1,3-dioxepan-4-yl, 1,3-dioxe-pan-5-yl, 1,3-dioxepan-6-yl, 1,3-dithiepan-2-yl, 1,3-dithie-20 pan-2-yl, 1,3-dithiepan-2-yl, 1,3-dithiepan-2-yl, 1,4-dioxe-pan-2-yl, 1,4-dioxepan-7-yl, hexahydroazepin-l-yl, hexahydroaze-pin-2-yl, hexahydroazepin-3-yl, hexahydroazepin-4-yl, hexahy-dro-1,3-diazepin-l-yl, hexahydro-1,3-diazepin-2-yl, hexahy-dro-1,3-diazepin-4-yl, hexahydro-1,4-diazepin-l-yl and hexahy-25 dro-1,4-diazepin-2-yl;
Examples of unsaturated heterocycles which can contain a carbonyl or thiocarbonyl ring member are:
dihydrofuran-2-yl, 1,2-oxazolin-3-yl, 1,2-oxazolin-5-yl, 1,3-oxa-30 zolin-2-yl;
Amongst the heteroaromatics, the 5- and 6 :~ cred ones are pre-ferred, e.g. furyl, such as 2-furyl and 3-furyl, thienyl, such as 35 2-thienyl and 3-thienyl, pyrrolyl, such as 2-pyrrolyl and 3-pyr-rolyl, isoxazolyl, such as 3-isoxazolyl, 4-isoxazolyl and 5-iso-xazolyl, isothiazolyl, such as 3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, pyrazolyl, such as 3-pyrazolyl, 4-pyrazolyl and 5-pyrazolyl, oxazolyl, such as.2-oxazolyl, 4-oxazolyl and 5-oxa-40 zolyl, thiazolyl, such as 2-th;A~olyl, 4-thiazolyl and 5-thiazo-lyl, imidazolyl, such as 2-;m;~Azolyl and 4-imidazolyl, OX~;A~O_ lyl, such as OxA~; A ~ol-3-yl~ 1,2,4- OxA~; A ~ol-5-yl and 1,3,4-oxa-diazol-2-yl, thiadiazolyl, such as 1,2,4-th; A~;A701 - 3 - yl, 1,2,4-th; A~; A ~ol-5-yl and 1,3,4-th; A~; A ~ol-2-yl, triazolyl, such 45 as 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl and 1,2,4-triazol-4-yl, - pyridinyl, such as 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, pyridazinyl, such as 3-pyridazinyl and 4-pyridazinyl, pyrimidi-nyl, such as 2-pyrimidinyl, 4-pyr;m;~inyl and 5-pyrimidinyl, fur-~ OOSO/46586 CA 0224~6~9 1998-08-06 , ._-thermore 2-pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl, in particular pyridyl, pyrimidyl, furanyl and thienyl.
All phenyl and heterocyclic rings are preferably unsubstituted or 5 have attached to them a cyano, nitro, halogen, C1-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, (Cl-C4-alkyl)car-bonyl, (C1-C4-alkoxy)carbonyl or (Cl-C4-alkyl)carbonyloxy sub-stituent.
Preferred with a view to the use of the substituted aromatic phosphonic acid derivatives I as herbicides or for the desicca-tion/defoliation of plants are those compounds I where the sub-stituents have the following m~n;ngS~ in each case alone or in 15 combination:
Eth is -CH2-CH(halogen)-, -CH2-CH(CN)-, -CH2-CH(COOCH3)-, -CH=CH-, -CH=C(halogen)-, -CH=C(CN)-, -CH=C(CH3)-, -CH=C(COOCH3)- or -C5C-, in particular -CH2-CH(halogen)- or -CH=C(halogen)-, particularly preferably -CH=C(halogen)-;
yl is oxygen;
y2 is oxygen;
Y3 is oxygen;
R1, R2, R6, R7 independently of one another are hydrogen, C1-C6-alkyl, Cl-C6-haloalkyl, hydroxy-Cl-C4-alkyl, cyano-Cl-C4-alkyl, Cl-C4-alkoxy-Cl-C4-alkyl, di(Cl-C4-alkyl)-amino--Cl--C4--alkyl,Cl--C4--alkylthio-Cl--C4-alkyl, Cl--C4--alkyl--f~ sulfonyl-Cl-C4-alkyl, Cl-C4-haloalkylsulfonyl-Cl-C4-alkyl, ' C3-C6-alkenyl, C3-C6-haloalkenyl, C3-C6-alkynyl, hydroxy-carbonyl--Cl--C4--alkyl,(Cl--C4--alkoxy)carbonyl--Cl--C4-alkyl, aminocarbonyl-Cl-C4-alkyl, (Cl-C4-alkyl)aminocarbonyl-Cl-C4-alkyl, di(Cl-C4-alkyl)aminocarbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-Cl-C4-alkyl, phenyl, phenyl-Cl-Cg-alkyl or 3- to 7-membered heterocyclyl or heterocyclyl-Cl-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or thiocarbonyl ring member, and it being possible for all cycloalkyl, phenyl and heterocyclyl rings to be unsubstituted or to have att~che~
to them one to four substituents, in each case selected from the group consisting of halogen, nitro, amino, hydroxyl, carboxyl, Cl-C4-alkyl, Cl-C4-haloalkyl, 0050/46586 CA 0224~6~9 l998-08-06 . 26 Cl-C4-alkoxy, Cl-C4-alkylsulfonyl, (C1-C4-alkyl)carbonyl, (Cl-C4-alkoxy)carbonyl and di(Cl-C4-alkyl)amino, or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethAne~;yl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four Cl-C4-alkyl and/or one or two (C1-C4-alkoxy)carbonyl groups, R1, R2, R6, R7 are, in particular, in each case hydrogen, Cl-C6-alkyl, Cl-C6-haloalkyl, C3-C6-alkenyl, C3-C6-haloalkenyl, C3-C6-alkynyl, (C3-C4-alkoxy)carbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-Cg-cycloalkyl-C1-Cq-alkyl, ~ phenyl, phenyl-C1-C4-alkyl or 3- to 7-membered heterocyclyl ' or heterocyclyl-C1-C4-alkyl or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethanediyl or 1,3-propylene chain;
R1, R2, R6, R7 is particularly preferably in each case hydrogen, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, phenyl or phenyl-Cl-C4-alkyl, or R1 and R2 together form a 1,3-propylene chain;
R3 is cyano, halogen or C1-C4-haloalkyl, in particular halogen, particularly preferably chlorine;
R4 is h.ydrogen, fluorine or chlorine, in particular fluorine or chlorine, particularly preferably fluorine;
R5 is one of the following heterocycles ~1 to ~5, ~7, ~20, ~21 . and ~22:
. 45 ~ 0050/46586 CA 02245659 l998-08-06 .
R9 N ~ 0 ~ N~ Rl ~ N' ~ ~3 ~ _ y4 R 6 Rl7 ,r Rl9 R18 R23 R~ N
N k ' Rs3 Rs2 ,~ Rsl \
S ~ N - ~50 ~20 ! ~ S
~ R54 N~
I S ~22 Rs6~ ~ N
where R8 is methyl;
R9 is Cl-C4-haloalkyl, in particular trifluoromethyl;
45 Rlo is Cl-C4-alkyl, in particular methyl;
0050/46586 CA 0224~6~9 1998-08-06 Rll is Cl-C4-haloalkyl, in particular trifluoromethyl, or Cl-C4-halo~lko~y, in particular difluoromethoxy;
Rl2 is halogen, in particular chlorine, or Cl-C4-haloalkyl, in particular trifluoromethyl;
Y4 is oxygen;
lO Rl3 and Rl4independently of one another are Cl-C4-alkyl, in particular methyl, or Rl3 and Rl4together with the ring atoms l;nk;ng them are a 6: '~red carbocyclic ring;
Rl5 and Rl6together with the ring atoms linking them are a 6 . --h~red carbocyclic ring;
20 Rl7 is halogen, in particular chlorine;
Rl8 is chlorine or bromine, in particular chlorine;
25 Rl9 is halomethyl, in particular difluoromethyl;
R20 is Cl-C4-alkyl, in particular methyl;
R23 and R24together with the ring atoms linking them are a 6-mem-bered ring;
~_. Y7 is oxygen;
35 R50 is Cl-C4-alkyl, in particular methyl;
Rsl is Cl-C4-haloalkyl, in particular trifluoromethyl;
Rs2 is hydrogen;
R53 and R54 together with the ring atoms l;nk;ng them are a 6-mem-bered ring;
45 Z3, z4 independently of one another are nitrogen;
~ 0050/46586 CA 0224~6~9 1998-08-06 .
R55 and R56 together with the ring atoms linking them are a 5- or 6 7 cred ring which, if desired, can additionally have attached to it one or two Cl-C4-alkyl substituents;
5 R5 is especially preferably 1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyri m; ~; ne~;on-3-yl, 4-chloro-5-difluoro-methoxy-1-methyl-lH-pyrazol-3-yl, 4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl, 1-methyl-4,5-di(trifluoromethyl)-lH-pyrazol-3-yl, 1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl, 10 3,4-dimethyl-lH-pyrrol-2,5-dion-1-yl, 3-chloro-4,5,6,7-tetra-hydro-2H-indazol-2-yl, 5-chloro-1-difluoromethyl-2-methyl-lH-~ ol-4-yl, 5,6,7,8-tetrahydro-1,2,4-triazolot4,3-a]pyridin-3(2H)-on-2-yl, (3-methyl-4-trifluoromethyl-2(3H)-thiazolyli-dene)amino, (tetrahydro-3-oxo-lH,3H-[1,3,4]th;~ zolo-15 [3,4-a]pyridazin-1-yl;~e)amino or (6,7-dihydro-6,6-dimethyl-r 3H, 5H ~yLLolo [ 2 ~ l--c ] t l, 2, 4 ] th; ~ ol--3--ylidene ) amino .
~.
Very especially preferred are the compounds IAa listed in Table 1 below (~ I where R3 = chlorine; Eth 5 -CH2-CH2-; R5 = heterocycle ~1 where R3 = CH3 and R9 = CF3):
~.
.
, 0050/46586 CA 02245659 l998-os-06 ~ . .
Table 1 ~ N
~ ~=O
~ N ~,1 IAa 10 R4 ~ CH2 CH~--' y Cl y3R2 15 No. R4 -P(=Yl)(y2Rl)(y3R2) LAa.l H -P(=O)(OH)2 IAa.2 H -p(=o)(ocH3)2 LAa.3 H -P(=O)(OC2Hs)2 IA~.4 H -p(=o)[o-(n-c3H7)]2 LAa.S H -P(=O)tOCH(CH3)2]2 LAa.6 H -P(=O)[O-(n-CiHs)]2 LAa.7 H -p(=o)[ocH2-cH(cH3)2]2 IAa.8 H -P(=O)[OCH(CH3)-C2H5]2 25 IA~.9 H -P(=0)(0CH2-CF3)2 IA~.10 H -P(=O)(OCH2-CH2-OH)2 IAa.ll H -p(=o)(ocH2-cH2-cN~2 L~a.12 H -p(=o)(ocH2-cH2-ocH3)2 30 IAa.13 H -p(=o)(ocH2-cH2-oc2H5)2 IAa.14 H -p(=o)(ocH2-cH2-ocF3)2 ,~ IAa.15 H -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 IAa.16 H -P(=O)(OCH2-CH2-OCH2-C----CH)2 35 IAa.17 H -P(=O)(OCH2-CH2-0-cyclopentyl~2 IAa.18 H -p(=o)(ocH2-cH2-NH2)2 IAa.l9 H -p(=o)(ocH2-cH2-NH-cH3)2 IAa.20 H -p(=o)[ocH2-cH2-N(cH3)2]2 LAa.21 H -P(=O)(OCH2-CH2-SCH3)2 40 L~a.22 H -P(=O)(OCH2-CH2-SC2H5)2 IAa.23 H -p(=o)(ocH2-cH2-scF3)2 IAa.24 H -P(=O)(OCH2-CH2-SCH2-CH=CH2)2 IAa.25 H -P(=O)(OCH2-CH2-SCH2-C----CH)2 45 IAa.26 H -P(=O)(OCH2-CH2-SO-CH3)2 IAa.27 H -p(=o)(ocH2-cH2-so-c2H5)2 IAa.28 H -p(=o)(ocH2-so2-cH3)2 0050/46586 CA 022456s9 1998-08-06 No. R4 _p(=yl)(Y2R1)(Y3R2) IAa.29 H -p(=o)(ocH2-so2-c2Hs)z IAa.30 H -p(=o)(ocH2-cH2-so2-cH3)2 IAa.31 H -p(=o)(ocH2-cH2-so2-c2Hs)2 IAa.32 H -p(=o)(ocH2-cH=cH2)2 IAa.33 H -P(=O)(OCH2-CH=CH-C~3)2 IAa.34 H -p(=o)(ocH2-cH2-cH=cH2)2 IAa.35 H -P(=O)(OCH2-CH=CH-Cl~Q
IAa.36 H -P(=O)(OCH2-C----CH)2 IAa.37 H -P(=O)[OCH~CH3)-C--CH]2 IAa.38 H -p(=o)(ocH2-co-ocH3)2 IAa.39 H -p(=O)(OCH2-CO-OC2Hs)2 IAa.40 H -P(=O)[OCH(CH3)-CO-OCH3]2 - IAa.41 H -P(=O)[OCH(CH3)-CO-OC2Hs]2 IAa.42 H -p(=o)(ocH2-co-N~2)2 IAa.43 H -p(=o)(ocH2-co-NH-c~3)2 IAa.44 H -p(=o)[ocH2-co-N(cH3)2]2 IAa.45 H -P(=O) OCH(CH3)-CO-N~2]2 IAa.46 H -P(=O) OCH(CH3)-CO-NH-C~]2 IAa.47 H -P(=O) OCH(CH3)-CO-N(CH3)2]2 2S IAa.48 H -P(=O)(O-cyclopropyl~Q
IAa.49 H -P(=O)(O-cyclobutyl~2 IAa.50 H -P(=O)(O-cyclopentyl~z IAa.51 H --P(=O)(O-cyclohexYl~2 IAa.52 H -P(=O)(OCH2-cyclopropyl~2 LAa.53 H -p(~o)(ocH2-cyclobutyl~2 ~IAa.54 H -p(=o)(ocH2-cyclopentyl~2 '~-IAa.55 H -p(=o)(ocH2-cyclohexyl~2 IAa.56 H -p(=o)(o-phenyl~2 3 5 L~a.57 H -p(=o)(ocH2-phenyl~2 IAa.58 H -P(=O)(O-oxetan-3-yl~
IAa.59 H --P(=O)(O-tetraLyd.ùru~ -2-yl~
IAa.60 H -P(=O)(O-tetrahy~l.ofu,dll-3-yl~
~,o IAa.61 H -P(=O)(O-tetrahyd.o~,y.~n-2-yl~
IAa.62 H -P(=O)(O-tetrahydlo~y.~n-3--yl~
IAa.63 H -P(=O)(O-tetraLyd.u~.y.~n-4-yl~
IAa.64 H -P(=O)(OCH2-o~iran-2-yl~
IAa.65 H -P(=O)(OCH2-oxetan--3-yl}~
IAa.66 H -P(=O)(OCH2-tetrahydrofuran-2-yl~
IAa.67 H -P(=O)(OCH2-tetrahydrofuran-3-yl~
0050/46586 CA 0224s6ss l998-08-06 No. R4 _p(=yl)cy2Rl)(y3R2) IAa.68 H --P(=O)(OCH2-pyrrolidin-l-ylk IAa.69 H -P(=O)[OCH2-(2-pyrrolidon-l-yl)~
5 IAa.70 H --P(=O)(OCH2-tetrahy~l~o~y~an-2-yl~
IAa.71 H -P(=O)(OCH2-tetral ylLo~y~an-3-yl~
IAa.72 H --P(=O)(OCH2-tetrally~1lo~-4-yl~2 IAa.73 H --P(=O)(OCH2-piperidin-l-yl~
IAa.74 H --P(=O)(OCH2--morpholin.-4-yl~
IAa.75 H -P(=O)(OH)(OCH3) IAa.76 H -P(=O)(OH)(OC2Hs) IAa.77 H --P(=O)(OH)[O-[n-C3H7)]
IAa.78 H -P(=O)(OH)[OCH(CH3)2]
15 IAa.79 H -P(=O)(OH)[O-(n-CiHg)]
~~IAa.80 H --P(=O)(OH)[OCH2-CH(CH3)2]
IAa.81 H -P(=O)(OH)[OCH(CH3)-c2Hs]
IAa.82 H -P(=O)(OH)(OCH2-CF3) 20 IAa.83 H -P(=O)(OH)(OCH2-CH2-OH) IAa.84 H -P(=O)(OH)(OCH2-CH2-CN) IAa.85 H -P(=O)(OH)(OCH2-CH2-OCH3) IAa.86 H -P(=O)(OH)(OCH2-CH2-OC2Hs) 25 IAa.87 H -P(=O)(OH)(OCH2-CH2-OCF3) IAa.88 H -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) LAa89 H -P(=O)(OH)(OCH2-CH2-OCH2-C-- CH~
LAa.90 H -P(=O)(OH)(OCH2-CH2-O-cyclopentyl) L~a.91 H -P(=O)(OH~(OCH2-CH2-NH2) IAa.92 H -P(=O)(OH)(OCH2-CH2-NH-CH3) IAa.93 H -P(=O)(OH)[OCH2-CH2-N(cH3)2]
IAa.94 H -P(=O)(OH)(OCH2-CH2-SCH3) IAa.95 H -P(=O)(OH9(0CH2-CH2-SC2Hs) 35 IAa.96 H -P(=O)(OH)(OCH2-CH2-SCF3) IAa.97 H -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.98 H -P(=O)(OH)(OCH2-CH2-SCH2-C_ CH) IAa.99 H -P(=O)(OH)(OCH2-CH2-SO-CH3) 40 IAa.100 H -P(=O)(OH)(OCH2-CH2-SO-C2Hs) IAa.101 H -P(=O)(OH)(OCH2-SO2-CH3) LAa.102 H -P(=O)(OH)(OCH2-SO2-C2Hs) IAa.103 H -P(=O)(OH)(OCH2-CH2-SO2-CH3) IAa.104 H -P(=O)(OH)(OCH2-CH2-SO2-C2Hs) IAa.105 H -P(=O)(OH9(0CH2-CH=CH2) IAa.106 H -P(=O)(OH)(OCH2-CH=CH-CH3) 0050/46586 CA 0224~6~9 l998-08-06 No. R4 -P(=yl)(y2Rl)(y3R2) L~a.107 H -P(=O)(OH)(OCH2-CH2-CH=CH2) L~a.108 H -P(=O)(OH)(OCH2-CH=CH-Cl) IAa.109 H -P(=O)(OH)(OCH2-C= CH) IAa.110 H -P(=O)(OH)[OCH(CH3)-C--CH]
LAa.111 H -P(=O)(OH)(OCH2-CO-OCH3) IAa.112 H -P(=O)(OH)(OCH2-CO-OC2Hs) L~a.113 H -P(=O)(OH)[OCH(CH3)-CO-OCH3]
IAa114 H ~p(=o)(oH)[ocH(cH3)-co-oc2Hs]
IAa.115 H -p(=o)(oH)(ocH2-co-NEI2) IAa.116 H -P(=O)(OH)(OCH2-CO-NH-CEO
IAa.117 H _p(=o)(oH)[ocH2-co-N(cH3)2]
IAa.118 H -P(=O)(OH)[OCH(CH3)-CO-NH2]
IAa.119 H -P(=O)(OH)[OCH(CH3)-CO-NH-C~]
IAa.120 H -P(=O)(OH)[OCH(CH3)-CO-N(CH3)2]
L~a.121 H -P(=O)(OH)(O-cyclopropyl) IAa.122 H -P(=O)(OH)(O-cyclobutyl) IAa.123 H -P(=O)(OH)(O-cyclopentyl) IAa.124 H -P(=O)(OH)(O-cyclohexyl) IAa.125 H -P(=O)(OH)(OCH2-cyclop}opyl) IAa.126 H -P(=O)(OH)(OCH2-cyclobutyl) IAa.127 H -P(=O)(OH)(OCH2-cyclopentyl) IAa.128 H -P(=O)(OH)(OCH2-cyclohe~cyl) IAa.129 H -P(=O)(OH)(O-phenyl) IAa.130 H -P(=O)(OH)(OCH2-phenyl) IAa.131 H -P(=O)(OH)(O-oxetan-3-yl) IAa.132 H -P(=O)(O~(O-tetrahyd.uru.dn-2-yl) IAa.133 H -P(=O)(OH)(O-tetrahylLoru~ -3-yl) IAa.134 H -P(=O)(OH)(O-tetral yd.u~gldn-2-yl) IAa.135 H -P(=O)(OH)(O-tetrahg~Lo~.an-3-yl) IAa.136 H -P(=O)(OH)(O-tetraLg~o~,g.dll-4-yl) IAa.137 H -P(=O)(OH)(OCH2-oxiran-2-yl) IAa.138 H -P(=O)(OH)(OCH2-o~etan--3--yl) IAa.139 H -P(=O)(OH)(OCH2-tetrahydrofuran-2-yl) IAa.140 H -P(=O)(OH)(OCH2-tetrahydrofuran-3-yl) IAa.141 H -P(=O)(OH)(OCH2-pyrrolidin-1-yl) IAa.142 H -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
IAa.143 H -P(=O)(OH)(OCH2-tetrahydropyran-2-yl) IAa.144 H -P(=O)(OH)(OCH2-tetrahyd.u~g.an-3-yl) IAa.145 H -P(=O)(OH)(OCH2-tetrahyd.o~y.dn-4-yl) 0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=yl)cy2Rl)~y3R2) IAa.146 H -P(=O)(OH)(OCH2-piperidin-l-yl) IAa.147 H -P(=O)(OH)(OCH2-morpholin-4-yl) IAa.148 H -p(=o)(ocH3)(oc2Hs) IAa.149 H -p(=o)(ocH3)[o-(n-c3H7)]
IAa.150 H -P(=Q)(0CH3)[0CH(CH3)2]
IAa.151 H -P(=O)(OCH3)[0-(n--C J,Hg)]
IAa.152 H -P(=0)(0CH3)[0CH2-CH(CH3)2]
IAa.153 H -P(=0)(0CH3)[0CH(CH3)-C2H5]
L~a.154 H -P(=O)(OCH3)(0CH2-CF3) IAa.155 H -P(=O)(OCH3)(0CH2-CH2-OH) L~a.156 H -P(=O)(OCH3)(0CH2-CH2-CN) 15 IAa.157 H -P(=O)(OCH3)(0CH2-CH2-OCH3) ~- IAa.158 H -P(=O)(OCH3)(0CH2-CH2-0C2Hs) IAa.159 H -P(=O)(OCH3)(0CH2-CH2-OCF3) L~a.160 H -P(=O)(OCH3)(0CH2-CH2-0CH2-cH=cH2) 20 IAa.161 H -P(=0)(0CH3)(0CH2-CH2-OCH2-C5 CH) IAa.162 H -P(=O)(OCH3)(0CH2-CH2-0-cyclopentyl) IAa.163 H -P(=0)(0CH3)(0CH2-CH2-NH2) IAa.164 H -P(=O)(OCH3)(0CH2-CH2-NH-CE0 25 IAa.165 H -P(=0)(0CH3)[0CH2-CH2-N(CH3)2]
IAa.166 H -P(=O)(OCH3)(0CH2-CH2-SCH3) IAa.167 H -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.168 H -P(=O)(OCH3)(0CH2-CH2-SCF3) IAa.169 H -p(=o)(ocH3)(ocH2-cH2-scH2-cH=cH2) IAa.170 H -P(=O)(OCH3)(0CH2-CH2-SCH2-C5 CH) f~ L~a.171 H -P(=O)(OCH3)(0CH2-CH2-SO-CH3) ~-; IAa.172 H -P(=0)(0CH3)(0CH2-CH2-S0-C2H5) IAa.173 H -P(=O)(OCH3)(OCH2-SO2-CH3) 35 IAa.174 H -P(=0)(0CH3)(0CH2-S02-C2Hs) IAa.175 H -P(=O)(OCH3)(0CH2-CH2-S02-CH3) IAa.176 H -P(=0)(0CH3)(0CH2-CH2-S02-C2H5) IAa.177 H -P(=O)(OCH3)(OCH2-CH=CH2) 40 IAa.l78 H -P(=O)(OCH3)(0CH2-CH=CH-CH3) IAa.179 H -P(=0)(0CH3)(0CH2-CH2-CH=CH2) IAa.180 H -P(=O)(OCH3)(OCH2-CH=CH-Cl) IAa.181 H -P(=O)(OCH3)(0CH2-C5 CH) IAa.182 H -p(=o)(ocH3)[ocH(cH3)-ce CH]
IAa.183 H -P(=O)(OCH3)(0CH2-C0-OCH3) IAa.184 H -P(=O)(OCH3)(OCH2-CO-OC2Hs) 0050~46586 CA 0224~6~9 l998-08-06 ~ . .
No. R4 -p(=yl)cy2Rl)cy3R2) IAa.185 H -P(=O)(OCH3) OCH(CH3)-CO-OCH3]
IAa.186 H -P(=O)(OCH3) OCH(CH3)-CO-OC2Hs]
IAa.187 H -P(=O)(OCH3)(0CH2-CO-NH2) IAa.188 H -P(=O)(OCH3)(0CH2-CO-NH-CH~) IAa.189 H -p(=o)(ocH3)[ocH2-co-N(c~l3)2]
IAa.l90 H -p(=o)(ocH3)tocH(cH3)-co-N~2]
IAa.l91 H -P(=O)(OCH3)[0CH(CH3)--CO-NH-C~]
IAa.192 H -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.193 H --P(=O)(OCH3)(0-cyclopropyl) IAa.194 H -P(=O)(OCH3)(0-cydobutyl) IAa.l95 H -P(=O)(OCH3)(0-cyclopentyl) IAa.196 H -P(=O)(OCH3)(0-cyclohe~yl) ~ IAa.197 H -P(=O)(OCH3)(0CH2-cyclopropyl) IAa.198 H -P(=O)(OCH3)(0CH2-cyclobutyl) IAa.l99 H -P(=O)(OCH3)~0CH2-cyclopentyl) IAa.200 H -P(=O)(OCH3)(0CH2-cydohe~yl) IAa.201 H -P(=O)(OCH3)(0-phenyl) IAa.202 H -P(=O)(OCH3)(0CH2-phenyl) IAa.203 H -P(=O)(OCH3)(0-oxetan-3-yl) IAa.204 H -P(=O)(OCH3)(0-tetral y.lloru.all-2-yl) IAa.205 H -P(=O)(OCH3)(0-tetraLy-i.orulan-3-yl) IAa.206 H -P(=O)(OCH3)(0-tetrahyd o~y.an-2-yl) IAa.207 H -P(=O)(OCH3)(0-tetrahyd~opy~àn-3-yl) IAa.208 H -P(=O)(OCH3)(0-tetraLyd.o~ylan-4--yl) IAa.209 H -P(=O)(OCH3)(0CH2-o~ciran-2-yl) ,~ IAa.210 H -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.211 H -P(=O)(OCH3)(0CH2-tetrahyd.vru.all-2-yl) IAa.212 H --P(=O)(OCH3)(0CH2--tetrahyd.vru.an-3-yl) IAa.213 H -P(=O)(OCH3)(0CH2-pyrrolidin-1-yl) IAa.214 H -P(=O)(OCH3)[0CH2-(2--pyrrolidon-l-yl)]
IAa.215 H -P(=O)(OCH3)(0CH2-tetrahy~vl,y.an-2-yl) IAa.216 H -P(=O)(OCH3)(0CH2-tetrahydlopylan-3-yl) IAa.217 H -P(=O)(OCH3)(0CH2-tetrahydlv~ylan~-yl) IAa.218 H -P(=O)(OCH3)(0CH2-piperidin-1-yl) IAa.219 H -P(=O)(OCH3)(0CH2-morpholin-4-yl) IAa.220 H -P(=o)(oc2Hs) O-(n-C3H7)]
IAa.221 H --P(=O)(OC2Hs) OCH(CH3)2]
IAa.222 H -P(=O)(OC2Hs) O-(n-(~Hs)]
IAa.223 H -P(=O)(OC2Hs) 0CH2-CH(CH3)2]
0050~46586 CA 0224~6~9 l998-08-06 No. R4 P(=Yl)CY2Rl)(y3Rz) LA~.224 H -p(=o)(oc2Hs)locH(cH3)-c2Hs]
LAa.225 H -P(=O)(OC2Hs)(OCH2-CF3) LA a.226 H -P(=O)(OC2H5)(0CH2-CH2-OH) LAa.227 H -P(=O)(OC2Hs)(OCH2-CH2-C~
LA~.228 H -P(=O)(OC2H5)(0CH2-CH2-OCH3) LAa.229 H -P(=O)(OC2Hs)(OCH2-CH2-OC2H5) LAa.230 H -P(=O)(OC2H5)(0CH2-CH2-OCF3) LAa.231 H -p(=o)(oc2H5)(ocH2-cH2-ocH2-cH=cH2) I~.232 H -P(=O)(OC2H5)(OCH2-CH2-OCH2-Ca CH) LAa.233 H -P(=O)(OC2H5)(0CH2-CH2-O-cyclopen~l) I~a.234 H -P(=O)(OC2H5)(0CH2-CH2-NH2) L9a.235 H -P(=O)(OC2H5)(0CH2-CH2--NH-CH3) LAa.236 H -P(=O)(OC2H5)[ocH2-cH2-N(cH3)2]
LAa.237 H -P(=O)(OC2H5)(0CH2-CH2-SCH3) LA~.238 H -P(=O)(OC2H5)(0CH2-CH2--SC2H5) I~.239 H -P(=O)(OC2H5)(OCH2-CH2-SCF3) LAa.240 H -P(=O)(OC2H5)(0CH2-CH2-SCH2-CH=CH2) LAa.241 H --P(=O)(OC2Hs)(OCH2--CH2--SCH2-Ca CH) LAa.242 H -P(=O)(OC2Hs)(OCH2-CH2--SO-CH3) I~.243 H -P(=O)(OC2H5)(OCHz-CH2 - SO-C2H5) LAa.244 H -P(=o)(oc2H5)(ocHz-so2-cH3) LAa.245 H -P(=O)(OC2H5)(0CH2-SOz-C2Hs) LAa.246 H -P(=O)(OC2H5)(0CH2--CH2-SO2-CH3) LAa.247 H -P(=O)(OC2H5)(ocH2-cH2 - SO2-C2H5) I~a.248 H -P(=O)(OC2Hs)(OCH2-CH=CHz) LAa.249 H -P(=O)(OC2Hs)(OCH2-CH=CH-CH3) ~_ LAa.250 H -p(=o)(oc2Hs)(ocH2-cH2-cH=cH2) I~a.251 H -P(=O)(OC2Hs)(OCH2-CH=CH-CI) LAa.252 H -P(=O)(OC2Hs)(OCH2-C - CH) I~a.253 H -P(=O)(OC2Hs)[oCH(CH3) - Ca CH]
I~.254 H -P(=O)(OC2H5)(OCH2-CO-OC~O
LAa.255 H -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~a.256 H -P(=O)(OC2H5)[0CH(CH3)-CO-OCH3]
I~.257 H -P(=O)(OC2H5)[OCH(CH3)-CO-OC2H5]
IAa.258 H -P(=O)(OC2H5)(0CH2-CO-NH2) LAa.259 H -P(=O)(OC2H5)(OCH2-CO-NH-CHO
LAa.260 H -p(=o)(oc2H5)[ocH2-co-N(c~3)2]
- IAa.261 H -P(=O)(OC2H5) OCH(CH3)-CO-NH2]
I~a.262 H -P(-O)(OC2H5) OCH(CH3)-CO-NH-CH3]
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)(y2R1)~3R2) IAa.263 H -p(=o)(oc2Hs)[ocH(cH3)-co-N(cH3)2]
IAa.264 H -P(=O)(OC2Hs)(O-cyclopropyl) 5 IAa.265 H -P(=O)(OC2Hs)(O-cyclobutyl) IAa.266 H -P(=O)(OC2Hs)(O-cyclopentyl) IAa.267 H ~P(=o)(oc2Hs)(o-cyclohexyl) IAa.268 H --P(=O)(OC2Hs)(OCH2-cyclop.. ,l,yl) IAa.269 H -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.270 H -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa271 H ~P(=o)(oc2Hs)(ocH2-cyclohe~yl) IAa.272 H -P(=O)(OC2Hs)(O-phenyl) IAa.273 H ~P(=o)(oc2Hs)(ocH2-phenyl) IAa.274 H --P(=O)(OC2Hs)(O-oxetan-3-yl) ,~ IAa.275 H --P(=O)(OC2Hs)(O-tetrahydloru.dn-2--yl) IAa.276 H -p(=o)(oc2Hs)(o-tetraLy~Loruldn-3-yl) IAa.277 H -P(=O)(OC2Hs)(O-tetrahy ~ o~y. an-2-yl) IAa.278 H -P(=O)(OC2Hs)(O--tetra~ydl~yldn--3-yl) IAa.279 H -P(=O)(OC2Hs)(O-tetrahyd.o~y.d.l-4-yl) IAa.280 H -P(=O)(OC2Hs)(OCH2-oxiran-2-yl) IAa.281 H ~P(=O)(oc2Hs)(ocH2-oxetan-3-yl) 2 5 IAa.282 H -P(=O)(OC2Hs)(OCH2-tetrahydrofuran--2-yl) IAa.283 H -P(=O)(OC2Hs)(OCH2-tetrahyd.c,ru~dn-3--yl) IAa.284 H ~P(=o)(oc2Hs)(ocHz-pyrrolidin-l--yl) IAa.285 H --P(=O)(OC2Hs)tOCH2-(2-pyrrolidon--1-yl)]
IAa.286 H -P(=O)(OC2Hs)(OCH2-tetrahyLo~,y.all-2-yl) IAa.287 H -P(=O)(OC2Hs)(OCH2-tetrahy&o~y.an-3-yl) IAa.288 H -P(=O)(OC2Hs)(OCH2-tetrahy~.opy.dn-4-yl) IAa.289 H --P(=O)(OC2Hs)(OCH2--pir~ri~lin--1--yl) IAa.290 H --P(=O)(OC2Hs)(OCH2-morpholin-4--yl) IAa.291 H -P(=0)(1,2-phenylenedio~y) IAa.292 H -P(=O)(O-CH2-CH2-O) IAa.293 H --P(=O) O--CH(CH3)--CH2-o]
IAa.294 H -P(=O) O-CH(CE~3)-CH(CH3)-O]
IAa.295 H -P(=O) O-CH(COOCH3)-CH(COOCH3)-O]
IAa.296 H -P(=O)~ O-C~2-CH2-CH2-O) IAa.297 H --P(=O)[O-CH-C(CH3)2-CH2--O]
IAa.298 H -P(=O)(O-C~2-CH2-CH2-CH2-O) 45 IAa.299 H -P(-S)(OH)2 IAa.300 H -P(=S)(OCH3)2 IAa.301 H --P(=S)(OC2Hs)2 -~ 38 -No. R4 -P(=yl)(y2Rl)(y3R2) IAa.302 H -P(=S)~O-(n-C3H7)]2 IAa.303 H -p(=s)[o-(n-~,H9)]2 S LAa.304 H -P(=s)(o-c~2-cH2-cH2-o) IAa.305 H -p(=o)(NH2)2 IAa.306 H -P(=O)(NH-CH3)2 IAa.307 H -p(=o)~N(cH3)2]2 L9a.308 H -p(=o)(NH-c2Hs)2 IAa.309 H -p(=o)[N(c2Hs)2]2 IAa.310 H -P(=O)(NH-CH2-CH=CH2)2 IAa.311 H -P(=O)(NH-CH2-C--CH)2 IAa.312 H -P(=O)(NH-cyclopropyl)2 IAa.313 H -p(=o)(NH-cE~2-cyclopentyl)2 C IAa.314 H --P(=O)(NH-phenylk IAa.315 H -p(=o)(NH-cH2-phenyl~2 IAa.316 H --P(=O)(pyrrolidin-1--yl~
IAa.317 H -P(=0)(2-meth~y~l,ol.ylyy.. olidin-1-yl~
IAa.318 H -P(=O)(NH-CH2-CO-OC~3)2 IAa.319 H --P(=O)[N(CH3)-CH2-CO-OCH3]2 IAa.320 H -p(=o)(NH-cK2-co-oc2Hs)2 2 5 IAa.321 H --P(=O)[N(CH3)-CH2-CO-Oc2Hs]2 IAa.322 H -P(=O)~NH-CH(CH33-CO-OCH3]2 IAa.323 H -P(=O)(OH)(NH2) IAa.324 H -P(=O)(OH)(NH-CH3) IAa.325 H -P(=O)(OH)rN(CH3)2]
IAa.326 H -P(=O)(OH)(NH-C2Hs) C IAa.327 H -P(=O)(OH)[N(C2Hs)2]
IAa.328 H -P(=O)(OH)(NH-CH2-CH=CH2) IAa.329 H -P(=O)(OH)(NH-CH2-C_ CH) 3 5 IAa.330 H -P(=O)(OH)(NH-cyclopropyl) L~a.331 H -P(=O)(OH)(NH-CH2-cyclopentyl) IAa.332 H -P(=O)(OH)(NH-phenyl) IAa.333 H -p(=o)(oH)(NH-cH2-phenyl) 40 IAa.334 H -P(=O)(OH)(pyrrolidin-1-yl) IAa.335 H -P(=O)(OH)(2-methoxyca-l,o~yl~,.olidin-1-yl) IAa.336 H -P(=O)(OH)(NH-CH2-CO-OCH3) IAa.337 H -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
45 IAa.338 H -P(=O)(OH)(NH-CE~z-CO-OC2Hs) IAa.339 H -P(=O)(OH) N(CH3)-CH2-CO-OC2Hs]
L~a.340 H -P(=O)(OH)-NH-CH(C~3)-CO-OC~3]
0050/46586CA 0224~6~9 l998-08-06 39 _ No.R4 _p(=yl)~Y2Rl)(Y3R2) IAa.341 H -P(=O)(OCH3)(NH2) IAa.342 H -P(=O)(OCH3)(NH-CH3) 5 IAa.343 H -P(=O)(OCH3)[N(CH3)2]
IAa.344 H -P(-O)(OCH3)(NH-C2Hs) IAa.345 H -P(=O)(OCH3)[N(C2Hs)2]
IAa.346 H -P(=O)(OCH3)~NH-CH2-CH=CH2) IAa.347 H -P(=O)(OCH3)~NH-CH2-CeCH) IAa.348 H -P(=O)(OCH3)~H-cyclopropyl) IAa.349 H -P(=O)(OCH3)~NH-CH2-cyclopentyl) IAa.350 H --P(=O)(OCH3)(NH-phenyl) IAa.351 H -P(=O)(OCH3)~NH-CH2-phenyl) 15 IAa.352 H -P(=O)(OCH3)(pyrrolidin-l-yl) f;IAa.353 H -P(=O)(OCH3)(2-metho~yc~l,ollyl~ olidirl-l-yl) IAa.354 H -P(=O)(OCH3)~#H-CH2-CO-OCH3) IAa.355 H -P(=O)(OCH3)~N(CH3)-CH2-CO-OCH3]
20 IAa.356 H -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.357 H -p(=o)(ocH3)[N(cH3)-cH2-co-oc2Hs]
IAa.358 H -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
IAa.359 H -p(=o)(oc2Hs)~NH2) 25 IAa.360 H -P(=O)(OC2Hs)(NH-CH3) IAa.361 H -p(=o)(oc2Hs)[N(cH3)2]
IAa.362 H -P(=O)(OC2Hs)(NH-C2Hs) IAa.363 H -p(=o)(oc2Hs)[N(c2Hs)2]
IAa.364 H -P(=O)(OC2Hs)(NH-CH2-CH=CH2) IAa.365 H -P(=O)(OC2Hs)(NH-CH2-C--CH~
IAa.366 H -P(=O)(OC2Hs)(NH-cyclopropyl) CIAa.367 H -P(=O)(OC2Hs)~NH-CH2-cyclopentyl) IAa.368 H ~P(=o)(oc2Hs)(NH-phenyl) 35 IAa.369 H -P(=O)(OC2Hs)(NH-CH2-phenyl) L~a.370 H -P(=O)(OC2Hs)(pyrrolidin-l-yl) IAa.371 H -P(=O)(OC2Hs)(2-metho~.l)ollyl~Jyl.olidin-l-yl) IAa.372 H -P(=O)(OC2Hs)(NH-CH2-CO-OC~3) 40 IAa.373 H -P(=O)(OC2Hs)[N(CH3)-CH2-CO-OCH3]
IAa.374 H -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.375 H -P(=O)(OC2Hs) N(CH3)-CH2-CO-OC2Hs]
IAa.376 H -P(=O)(OC2Hs) NH-CH(CH3)-CO-OCH3]
45 IAa.377 H - P(=O) N(CH3)2](0cH3) IAa.378 H -P(=O) N(CH3)2](0C2Hs) IAa.379 H --P(=O) N(CH3)2][0-(n-C3H?)]
0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=yl)(y2Rl)~y3R2) IAa.380 H --P(=O)[N(CH3)2][0CH(CH3)2]
IAa.381 H -P(=o)[N(cH3)2][o-(n-ciHs)]
IAa.382 H -P(=O)[N(CH3)2](0CH2-CH=CH2) IAa.383 H --P(=O)[N(CH3)2 (OCH2-Ca CH) IAa.384 H -P(=O)[N(CH3)2 (O-cyclohe~yl) IAa.385 H -P(=O)[N(CH3)2 (OCH2-cyclohe~yl) IAa.386 H -P(=O)[N(CH3)2 (O-phenyl) IAa.387 H -P(=O)[N(CH3)2 (OCH2-phenyl) IAa.388 H -P(=O)[N(CH3)2 (O-tetrahy~L. ruldn-2-yl) IAa.389 H ~p(=o)[N(cH3)2](ocH2-o~e IAa.390 H -P(=O)[N(CH3)2](0CH2-CF3) IAa.391 H -P(=O)[N(CH3)2](0CH2-CO-OCH3) ~- IAa.392 H -P(=O)[N(CH3)2](0CH2-CO-OC2H5) IAa.393 H -P(=O)(NH-CH2-CH2-O) IAa.394 H -P(=O)(NH-CH2-CH2-NH) IAa.395 H -P(=O)[N(CH3)-CH2-CH2-N(CH3)]
IAa.396 H -P(=O)(NH-CH2-CH2-CH2-O) IAa.397 H -P(=O)(NH-CH2-CH2-CH2-NH) IAa.398 H -P(=O)[N(CH3)-CH2-CH2-CH2-N(CH3)]
25 IAa.399 H -P(=O)[O-CH2-CH(CH3)-cH2-O]
IAa.400 H -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.401 H -P(=O) N(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.402 H -P(=O) NH-CEI2-CH2-CH2-CH2-O]
IAa.403 H -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.404 H -P(=S)~NH2)2 IAa.405 H -P(-S)~NH-CH3)2 CIAa.406 H -P(=S)~N(CH3)2]2 IAa.407 H -P(=S)~NH-C2Hs)2 35 IAa.408 H -P(=S)[N(C2Hs)2]2 IAa.409 H -P(=S)(NH-CH2-CH2-CH2-O) IAa.410 H -P(=S)(NH-CE~2-CH2-CH2-NH) IAa.411 H -P(=S)[N(CH3)-CH2-CH2-CH2-N(CH3)]
40 IAa.412 H -P(=O)(SCH3)2 IAa.413 H -P(=O)(SC2Hs)2 IAa.414 H -P(=O) S-(n-C3H7)]2 IAa.415 H --P(=O) SCH(CH3)2]2 IAa.416 H -P(=O) S-(n-~Hs)]2 IAa.417 H -P(=O)(SCH2-CH=CH2)2 LAa.418 H -P(=O)(S-phenyl~2 0050/46~86 CA 0224~6~9 l998-08-06 .
No. R4 P(=Yl)(Y2Rl)(Y3RZ) LAa.419 H -P(=O)(ScH2-phenyl~2 IAa.420 H -p(=o)(scH2-co-ocH3)2 5 LAa.421 H -p(=o)(scH2-co-oc2Hs)2 LAa.422 H -p(=o)(s-cH2-cH2-cH2-s) IAa.423 H -P(=O)(S-CHz-CH2-CH2-O) IAa.424 H -P(=S)(SCH3)2 IAa.425 H -P(=S)(SCzHs)2 IAa.426 H -P(=S)[S-(n-CaH7)]2 IAa.427 H -P(=S)~S-n-~Hs)]2 LAa.428 H -P(=S)(S-CH2-CH2-CH2-S) IAa.429 H -P(=S)(S-CHz-CH2-CH2-O) 15 IAa.430 Cl _p(=o)(oH)2 -~ IAa.431 Cl _p(=O)(OCH3)2 ~IAa.432 Cl -P(=o)(oc2Hs)2 IAa.433 Cl _p(=O)[O-(n-~H7)]2 20 IAa.434 Cl _p(=O)[OCH(CH3)2]2 IAa.435 Cl _p(=o) ~-(n-~Hs)]2 LAa.436 Cl -P(=O) OCH2-CH(CH3)2]2 LAa.437 Cl -P(=O) OCH(CH3)-C2H5]2 25 IAa.438 Cl _p(=O)(OCH2-CF3)2 LAa.439 Cl -P(=O)(OCH2-CH2-OH~2 IAa.440 Cl _p(=O)(OCH2-CH2-CN~2 IAa.441 Cl -P(=O)(OCH2-CH2-OCH3)2 IAa.442 Cl -P(=O)(OCH2-CH2-OC2H5)2 30 IAa.443 Cl -P(=O)(OCH2-CH2-OCF3)2 f~ IA~.444 Cl -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 ~- IAa.445 Cl -P(=O)(OCH2-CH2-OCH2-C----CH)2 IAa.446 Cl -P(=O)(OCH2-CH2-O-cyclopentyl~
35 L~a.447 Cl -p(=o)(ocH2-cH2-NH2)2 IAa.448 Cl -P(=O)(OCH2-CH2-NH-CH3)2 LAa.449 Cl -P(=O)[OCH2-CH2-N(CH3)2]2 IAa.450 Cl _p(=o)(ocH2-cH2-scH3)2 40 L~a.451 Cl -P(=O)(OCH2-CH2-SC2H5)2 IAa.452 Cl -P(=O)(OCH2-CH2-SCF3)2 IAa.453 Cl -P(=O)(OCH2-CH2-SCH2-CH=CH2)2 IAa.454 Cl -P(=O)(OCH2-CH2-SCH2-C----CH)2 45 IAa.455 Cl -P(=O)(OCH2-CH2-SO-CH3)2 -IAa.456 Cl -P(=O)(OCH2-CH2-SO-C2H5)2 IAa.457 Cl _p(=O)(OCH2-SO2-CH3)2 0050/46586 CA 02245659 l998-08-06 No. R4 --p(=yl)(Y2R1)(Y3R2) LAa.458 Cl -P(=O)(OCH2-SO2-C2Hs)2 IAa.459 Cl -P(=O)(OCH2-CH2-S02-CH3)2 LAa.460 Cl -P(=O)(OCH2-CH2-S02-C2Hs)2 LAa.461 Cl -P(=O)(OCH2-CH=CH2)2 IAa.462 Cl -P(=O)(OCH2-CH=CH-CH3)2 IAa.463 Cl --P(=O)(OCH2-CH2-CH=CH2)2 IAa.464 Cl -P(=O)(OCH2-CH=CH-Cl~Q
IAa.465 Cl -P(=O)(OCH2-C--CH)2 IAa.466 Cl _p(=o)[ocH(cH3)-c--CH]2 IAa.467 Cl -P(=O)(OCH2-CO-OCH3)2 IAa.468 Cl -P(=O)(OCH2-CO-OC2H5)2 IAa.469 Cl -P(=O) OCH(CH3)-CO-OCH3]2 ,~ IAa.470 Cl -P(=O) OCH(CH3)-CO-OC2H5]2 IAa.471 Cl _p(=O)(OCH2-CO-N~2)2 IAa.472 Cl --P(=O)(OCH2-CO-NH-C~3)2 IAa.473 Cl --P(=O)[OCH2-CO-N(CE~3)2]2 IAa.474 Cl -P(=O)[OCH(CH3)-CO-N~2]2 IAa.475 Cl --P(=O) OcH(cH3)-co-NH-cE~]2 IAa.476 Cl -P(=O) OCH(CH3)-CO-N(CH3)2]2 25 IAa.477 Cl -P(=O)(O-cyclopropyl~e IAa.478 Cl -P(=O)(O-cyclobutyl~z IAa.479 Cl -P(=O)(O-cyclopentyl~e IAa.480 Cl --P(=O)(O-cyclohe~yl~2 IAa.481 Cl -p(=o)(ocH2-cyclopropyl)2 IAa.482 Cl -P(=O)(OCH2--cyclobutYl)2 r.IAa.483 Cl --p(=o)(ocH2-cydopentyl~2 IAa.484 Cl -p(=o)(ocH2-cyclohexyl)2 IAa.485 Cl --P(=O)(O-phenyl~Q
3 5 IAa.486 Cl --P(=O)(OCH2--phenyl)2 IAa.487 Cl -P(=O)(O-oxetan-3-yl~
IAa.488 Cl -P(=O)(O-tetrahyd.oru~ -2--yl~
IAa.489 Cl -P(=O)(O-tetrahydrofuran-3-yl~
40 IAa.490 Cl -P(=O)(O-tetral ydlopyldn-2-yl~
IAa.491 Cl -P(=O)(O-tetral.ydl o~y I an-3-yl~
IAa.492 Cl -P(=O)(O-tetrahydlo~.yl~l-4-yl~
IAa.493 Cl -P(=O)(OCH2-oxiran-2-yl~
IAa.494 Cl -P(=O)(OCH2-oxetan-3-yl~?
IAa.495 Cl -P(=O)(OCH2-tetrah~dlorulaJl-2-yl~
IAa.496 Cl -P(=O)(OCH2-tetrahydrofuran-3-yl~
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 -p(=yl)(y2Rl)(y3R2) IAa.497 Cl -P(=O)(OCH2-pyrrolidin-l-yl~
IAa.498 Cl -P(=O)[OCH2-(2-py~olidon-l-yl)~
5 IAa.499 Cl -P(=O)(OCH2-tetrahyd,o~y.an-2-yl~
IAa.S00 Cl -P(=O)(OCH2-tetrahy~o~yldn-3-yl~
IAa.501 Cl -p(=o)(ocH2-tetrahyd,o~y,an-4 IAa.502 Cl -P(=O)(OCH2-piperidin-l-yl~
L~a.503 Cl -P(=O)(OCH2-morpholin-4-yl~
IAa.504 Cl -P(=O)(OH)(OCH3) IAa.505 Cl -P(=O)(OH)(OC2Hs) IAa.506 Cl -P(=O)(OH)[O-[n-C3H7) IAa.507 Cl _P(=O)(OH) OCH(CH3)2 15 IAa.508 Cl -P(=O)(OH) O-(n-~Hs)~
.J-IAa.509 Cl -P(=O)(OH) OCH2-CH(CH3)2]
L~a.510 Cl -P(=O)(OH) OCH(CH3)-C2Hs]
IAa.511 Cl _p(=O)(OH)(OCH2-CF3) 20 IAa.512 Cl -P(=O)(OH)(OCH2-CH2-OH) IAa.513 Cl -P(=O)(OH)(OCH2-CH2-CN) IAa.514 Cl -P(=O)(OH)(OCH2-CH2-OCH3) IAa.515 Cl -P(=O)(OH)(OCH2-CH2-OC2Hs) IAa.516 Cl -P(=O)(OH)(OCH2-CH2-OCF3) IAa.517 Cl -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) IAa.518 Cl -P(=O)(OH)(OCH2-CH2-OCH2-C-- CH) IAa.Sl9 Cl -P(=O)(OH9(0CH2-CH2-O-cyclopentyl) IAa.520 Cl -P(=O)(OH)(OCH2-CH2-NH2) IAa.521 Cl -P(=O)(OH)(OCH2-CH2-NH-CH3) f_IAa.522 Cl -P(=O)(OH)~OCH2-CH2-N(CH3)2]
IAa.523 Cl -P(=O)(OH)(OCH2-CH2-SCH3) IAa.524 Cl -P(=O)(OH)(OCH2-CH2-SC2HS) 35 IAa.525 Cl -P(=o)(oH)(ocH2-cH2-scF3) IAa.526 Cl -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.527 Cl -P(=O)(OH)(OCH2-CH2-SCH2-C-- CH) IAa.528 Cl -P(=O)(OH)(OCH2-CH2-SO-CH3) 40 IAa.529 Cl -P(=O)(OH)(OCH2-CH2-SO-C2Hs) IAa.530 Cl -P(=O)(OH)(OCH2-SO2-CH3) IAa.531 Cl -P(=O)(OH)(OCH2-SO2-C2Hs) IAa.532 Cl -P(=O)(OH)(OCH2-CH2-SO2-CH3) IAa.533 Cl -P(=o)(oH)(ocH2-cH2-so2-c2Hs) IAa.534 Cl -P(=O)(OH)(OCH2-CH=CH2) IAa.535 Cl -P(=O)(OH~(OCH2-CH=CH-CH3) 0050/46586 CA 0224~6~9 1998-08-06 No. R4 _p(=y1)(Y2Rl)(Y3R2) IAa.536 Cl -P(=O)(OH)(OCH2-CH2-CH=cH2) IAa.537 Cl -P(=O)(OH)(OCH2-CH=CH-Cl) 5 IAa.538 Cl -P(=O)(OH)(OCH2-C--CH) IAa.539 Cl -P(=O)(OH)tOCH(CH3)-C_ CH]
IAa.540 Cl -P(=O)(OH)(OCH2-CO-OCH3) IAa.541 Cl --P(=O)(OH)(OCHz-CO-OC2Hs) IAa.542 Cl -P(=O)(OH)[OCH(CH3)-CO-OCH3]
IAa.543 Cl -P(=O)(OH)[OCH(CH3)-CO-OC2Hs]
IAa.544 Cl --P(=o)(oH)(ocH2-co-N~2) IAa.545 Cl -P(=O)(OH)(OCH2-CO-NH-CH3) IAa.546 Cl -P(=O)(OH)[OCH2-CO-N(CH3)2]
15 IAa.547 Cl -P(=O)(OH)[OCH(CH3)-CO-NH2]
' IAa.548 Cl -P(=O)(OH)[OCH(CH3)-CO-NH-CH3]
IAa.549 Cl _p(=O)(O~[OCH(CH3)-CO-N(CH3)2]
IAa.550 Cl --P(=O)(OEl)(O-cyclopropyl) 20 IAa.551 Cl -P(=O)(OH)(O-cyclobutyl) IAa.552 Cl --P(=O)(OH)(O-cyclopentyl) IAa.553 Cl -P(=O)(OH)(O-cyclohe~yl) IAa.554 Cl -P(=O)(OH)(OCH2-cydop}opyl) 2 5 IAa.SSS Cl -P(=O)(OH)(OCH2-cyclobutyl) LAa.556 Cl -P(=O)(OH)(OCH2-cyclopentyl) IAa.557 Cl -P(=O)(OH)(OCH2-cyclohexyl) IAa.558 Cl -P(=O)(OH)(O-phenyl) IAa.SS9 Cl -P(=O)(OH)(OCH2-phenyl) IAa.560 Cl --P(=O)(OH)(O-oxetan-3-yl) fIAa.561 Cl -P(=O)(OH)(O-tetrahy-h~/ru.all-2-yl) ;~--IAa.562 Cl -P(=O)(OH)(O-tetrahyd.oru~ -3-yl) IAa.563 Cl --P(=O)(OH)(O-tetraLyd~ol,y~a-~-2-yl) 35 IAa.564 Cl -P(=O)(OH)(O-tetrahyd.~,~ylan-3-yl) IAa.565 Cl -P(=O)(OH)(O-tetrahyd o~y-dn-4-yl) IAa.566 Cl -P(=O)(OH)(OCH~-o~iran-2-yl) IAa.567 Cl -P(=O)(OH)(OCH2-oxetan-3-yl) 40 IAa.568 Cl -P(=O)(OH)(OCH2--tetrahyd.oru.~.n-2-yl) IAa.569 Cl -P(=O)(OH)(OCH2-tetrahyd oL.an-3-yl) IAa.570 Cl --P(=O)(OH)(OCH2-pyrrolidin-1--yl) IAa.571 Cl -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
45 IAa.572 Cl -P(=O)(OH)(OCH2-tetrahyd~opy.dll-2-yl) IAa.573 Cl --P(=O)(OH)(OCH2--tetrahy~l.o~y~dn-3-yl) IAa.574 Cl --P(=O)(OH)(OCH2-tetraLy.l.o~y.an-4-yl) 0050/46586 CA 0224~6~9 1998-08-06 o No. R4 _p(=yl)cy2Rl)(y3R2) IAa.575 Cl -P(=O)(OH)(OCH2-piperidin-l-yl) LAa.576 Cl -P(=O)(OH)(OCH2-morpholin-4-yl) 5 IAa.577 Cl _p(=o)(ocH3)(oc2H5) IAa.578 Cl -p(=o)(ocH3)[o-(n-c3H7)]
IAa.579 Cl _p(=o)(OCH3)[0CH(CH3)2]
IAa.580 Cl ~P(=o)(ocH3)[o-(n-c4H9)]
IAa.581 Cl -P(=O)(OCH3)[OCH2-CH(CH3)2]
IAa.582 Cl -P(=o)(ocH3)[ocH(cH3)-c2Hs]
L~a.583 Cl _p(=o)(ocH3)(ocH2-cF3) IAa.584 Cl -P(=O)(OCH3)(OCH2-CH2-OH) IAa.585 Cl -P(=O)(OCH3)(0CH2-CH2-CN~
15 IAa.586 Ci -P(=O)(OCH3)(OCH2-CH2-OCH3) ~~IAa.587 Cl ~p(=o)(ocH3)(ocH2-cH2-oc2Hs) IAa.588 Ci -P(=O)(OCH3)(OCH2-CH2-OCF3) IAa.589 Cl -p(=o)(ocH3)(ocH2-cH2-ocH2-cH=cH2) 20 IAa.590 Ci -P(=O)(OCH3)(0CH2-CH2-OCH2-C-- CH~
IAa.591 Cl -P(=O)(OCH3)(OCH2-CH2-O-cyclopentyl) IAa.592 Cl -P(=O)(OCH3)(OCH2-CH2-NH2) IAa.593 Ci -P(=O)(OCH3)(OCH2-CH2-NH-CH3) 25 L~a594 Cl -p(=o)(ocH3)[ocH2-cH2-N(cH3)2]
IAa.S9S Ci -P(=O)(OCH3)(OCH2-CH2-SCH3) IAa.596 Ci -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.597 Ci -P(=O)(OCH3)(OCH2-CH2-SCF3) IAa.598 C~ -p(=o)(ocH3)(ocH2-cH2-scH2-cH=cH2) IAa.S99 Cl -P(=O)(OCH3)(0CH2-CH2-SCH2-C----CH) f~IAa.600 Ci -P(=O)(OCH3)(OCH2-CH2-SO-CH3) '--L~a.601 Ci -p(=o)(ocH3)(ocH2-cH2-so-c2Hs) IAa.602 Ci -P(=o)(ocH3)(ocH2-soz-cH3) 35 IAa.603 Ci -P(=O)(OCH3)(OCH2-SO2-C2Hs) IAa.604 Cl -P(=O)(OCH3)(OCH2-CH2-SO2-CH3) IAa.605 Ci -P(=O)(OCH3)(OCH2-CH2-SO2-C2Hs) IAa.606 Ci -P(=o)(ocH3)(ocH2-cH=cH2) 40 IAa.607 Ci -P(=O)(OCH3)(OCH2-CH=CH-CH3) IAa.608 Ci -P(=O)(OCH3)(OCH2-CH2-CH=CH2) IAa.609 Cl -P(=O)(OCH3)(OCH2-CH=CH-Ci) IAa.610 Ci -P(=O)(OCH3)(OCH2-C- CH) IAa.611 Ci --P(=O)(OCH3)[0CH(CH3)-C--CH]
IAa.612 Cl -P(=O)(OCH3)(OCH2-CO-OCH3) IAa.613 Ci -P(=O)(OCH3)(OCH2-CO-OC2Hs) 0050/46586 CA 0224~6~9 1998-08-06 No. R4 --p(=yl)(Y2R1)(Y3R2) L4a.614 Cl -P(=O)(OCH3)[0CH(CH3)-CO-OCH3]
IAa.615 Cl -P(=O)(OCH3)[0CH(CH3)-CO-OC2Hs]
L~a.616 Cl -p(=o)(ocH3)(ocH2-co-N~2) IAa.617 Cl -P(=O)(OCH3)(0CH2-CO-NH-C~) IAa.618 Cl -P(=O)(OCH3) 0CH2-CO-N(CH3)2]
IAa.619 Cl -P(=O)(OCH3) OCH(CH3)-CO-NEI2~
IAa.620 Cl -P(=O)(OCH3) OCH(CH3)-CO-NH-CE~]
IAa.621 Cl -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.622 Cl -P(=O)(OCH3)(0-cyclopropyl) IAa.623 Cl -P(=O)(OCH3)(0-cyclobutyl) IAa.624 Cl --P(=O)(OCH3)(0-cyclopentyl) IAa.625 Cl -P(=O)(OCH3)(0-cyclohe~yl) f: IAa.626 Cl -P(=O)(OCH3)(0CH2-cydopropyl) L4a.627 Cl -P(=O)(OCH3)(0CH2-cyclobutyl) IAa.628 Cl -P(=O)(OCH3)(0CH2-cyclopentyl) L4a.629 Cl -P(=O)(OCH3)(0CH2-cyclohexyl) IAa.630 Cl -P(=O)(OCH3)(0-phenyl) IAa.631 Cl -P(=O)(OCH3)(0CH2-phenyl) IAa.632 Cl -P(=O)(OCH3)(0-oxetan-3-yl) 2 5 IAa.633 Cl -P(=O)(OCH3)(0-tetrahylL Oru. an-2-yl) LAa.634 Cl -P(=O)(OCH3)(0-tetral yd.vrulall-3-yl) IAa.635 Cl -P(=O)(OCH3)(0-tetrallyd o~yl~-2-yl) IAa.636 Cl -P(=O)(OCH3)(0-tetrahydlv~,y.dn-3-yl) IAa.637 Cl -P(=O)(OCH3)(0-tetrahy d. ~y. dn-4--yl) IAa.638 Cl -P(=O)(OCH3)(0CH2-o~iran-2-yl) ~_ IAa.639 Cl -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.640 Cl -P(=O)(OCH3)(0CH2-tetrahydrofuran--2--yl) IAa.641 Cl -P(=O)(OCH3)(0CH2-tetrally~;Lvru.~-3-yl) 3 5 IAa.642 Cl -P(=O)(OCH3)(0CH2-pyrrolidin-1-yl) IAa.643 Cl -P(=O)(OCH3)[0CH2-(2-pyrrolidon-1-yl)]
IAa.644 Cl --P(=O)(OCH3)(0CH2-tetraLy~Lvl,y.d.l-2-yl) IAa.645 Cl -P(=O)(OCH3)(0CH2-tetrahyd.vpy.dn-3-yl) IAa.646 Cl -P(=O)(OCH3)(0CH2-tetrahy~v~.y.dll~-yl) IAa.647 Cl -P(=O)(OCH3)(0CH2-piperidin--1--yl) IAa.648 Cl -P(=O)(OCH3)(0CH2-morpholin-4-yl) IAa.649 Cl -P(=O)(oc2Hs)[o-(n-c3H7)]
IAa.650 Cl -P(=o)(oc2Hs)[ocH(cH3)2]
IAa.651 Cl --P(=~)(~C2Hs)[~-(n-ciHs)]
IAa.652 Cl -P(=o)(oc2Hs)[ocH2-cH(cH3)2]
0050/46586 CA 0224~6~9 1998-08-06 ~ . . .
No. R4 --P(=Yl)CY2Rl)~y3R2) LA a.653 Cl -P(=O)(OC2H5)[0CH(CH3)-C2H5]
5LAa.654 Cl -P(=o)(oc2Hs)(ocH2-cF3) LAa.655 Cl -P(=O)(OC2Hs)(OCH2-cH2-OH) LAa.656 Cl -P(=O)(OC2Hs)(OCH2-CH2-C~
LA~.657 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCH3) 10LAa.6$8 Cl -P(=O)(OC2Hs)(OCH2-CH2-OC2H5) LAa.659 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCF3) I~a.660 Cl --P(=O)(OC2Hs)(ocH2-cH2-ocH2-cH=cH2) I~a.661 Cl -P(=O)(OC2Hs)(OCH2-CH2-OCH2-C--CH) LAa.662 Cl -P(=O)(OC2Hs)(OCH2-CH2-O-cyclopentyl) I~a.663 Cl -P(=o)(oc2Hs)(ocH2-cH2-NH2) LAa.664 Cl -P(=O)(OC2Hs)(OCH2-CH2-NH-CH3) LAa.665 Cl -P(=o)(oc2Hs)[ocH2-cH2-N(cH3)2]
LAa.666 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH3) 20LAa.667 Cl -P(=O)(OC2H5)(0CH2-CH2-SC2H5) LAa.668 Cl -P(=O)(OC2Hs)(OCH2-CH2-SCF3) I~a.669 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH2-CH=CH2) LAa.670 Cl -P(=O)(OC2H5)(0CH2-CH2-SCH2-C----CH) 25LAa.671 c~ -P(=O)(OC2H5)(0CH2-CH2-SO-CH3) LAa.672 Cl -P(=O)(OC2Hs)(OCH2-CH2-SO-C2H5) LAa.673 Cl -P(=O)(OC2Hs)(OCH2-SO2-CH3) LAa.674 Cl --P(=O)(OC2H5)(0CH2--S02 - c2H5) 30LAa.675 Cl -P(=O)(OC2Hs)(OCH2-CH2-SO2-CH3) LAa.676 Cl -P(=O)(OC2H5)(0CH2-CH2-SO2-C2H5) -- LAa.677 Cl -p(=O)(OC2H5)(0CH2-CH=cH2) a.678 Cl -P(=O)(OC2H5)(0CH2-CH=CH-CH3) LAa.679 Cl -P(=o)(oc2H5)(ocH2-cH2-cH=cH2) 35LAa.680 Cl -P(=O)(OC2H5)(0CH2-CH=CH-Cl) LAa.681 Cl -P(=O)(OC2H5)(0CH2-C2 CH) LAa.682 Cl -P(=O)(OC2H5)[0CH(CH3)-C--CH]
LAa.683 Cl -P(=O)(OC2H5)(0CH2-CO-OCH3) 40I~a.684 Cl -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~a.685 Cl -P(=O)(OC2H5)[0CH(CH3)-CO-OCH3]
LAa.686 Cl --P(=O)(OC2H5)[0CH(CH3)--CO--OC2H5]
I~a.687 Cl -P(=O)(OC2H5)(0CH2-CO-NH2) 45I~a.688 Cl -P(=O)(OC2H5)(0CH2-CO-NH-C~) I~a.689 Cl -P(=O)(OC2H5) OcH2-co-N(cH3)2]
LAa.690 Cl --P(=O)(OC2HS) OCH(CH3)-CO--N~2]
, 48 _ No. R4 _p(=yl)(y2R1)~y3R2) IAa.691 Cl -P(=O)(OC2Hs)[OCH(CH3)-CO-NH-C~g]
L~a.692 Cl -P(=O)(OC2Hs)[OCH(CH3)-CO-N(CH3)2]
5 IAa.693 Cl -P(=O)(OC2Hs)(O-cyclopropyl) L~a.694 C~ -P(=O)(OC2Hs)(O-cyclobutyl) IAa.695 Cl -P(=O)(OC2Hs)(O-cyclopentyl) L~a.696 Cl -P(=O)(OC2Hs)(O-cyclohexyl) IAa.697 Cl -P(=o)(oc2Hs)(ocH2-cyclopropyl) IAa.698 Cl -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.699 Cl -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa.700 Cl -P(=O)(OC2Hs)(oCH2-cydohe~yl) LAa.701 - Cl ~P(=O)(~C2Hs)(O-phenyl) 15 IAa.7o2 Cl ~P(=o)(oc2Hs)(ocH2-phenyl) IAa.703 Cl -P(=O)(OC2Hs)(O-o~etan-3-yl) L~a.704 Cl -P(=O)(OC2Hs)(O-tetrahy~oruldn-2-yl) IAa.705 Cl -P(=O)(OC2Hs)(O-tetrahy~oru-d~-3-yl) 20 LAa.706 Cl -P(=O)(OC2Hs)(O-tetrahy~o~ylan-2-yl) IAa.707 Cl -p(=o)(oc2Hs)(o-tetrahy~o~ylan-3-yl) LQa.708 Cl -P(=O)(OC2Hs)(O-tetrahy~o~ylan-4-yl) LAa.709 Cl -P(=O)(OC2Hs)(OCH2-o~ran-2-yl) 25 IAa.710 Cl -P(=O)(OC2Hs)(OCH2-oxetan-3-yl) IAa.711 Cl -P(=O)(OC2Hs)(OCII2 t~tlohy~orulan-2-yl) IAa.712 Cl -P(=O)(OC2Hs)(OCH2-tetrahydrofuran-3-yl) IAa.713 Cl -P(=O)(OC~Hs)(OCH2-py~olidin-l--yl) IAa.714 Cl -P(=O)(OC2Hs)[OCH2-(2-py~olidon-1-yl)]
IAa.715 Cl -P(=O)(OC2Hs)(OCH2-tetrahy~u,uylan-2-yl) ~,IAa.716 C~ -P(=O)(OC2Hs)(OCH2-tetrahy&u~ldn-3-yl) i LAa.717 C~ -P(=O)(OC2Hs)(OCII2 t~h~hy~u~yl~n-4-yl) IAa.718 Cl -P(=O)(OC2Hs)(OCH2-piperidin-1-yl) 35 IAa.719 Cl -P(=O)(OC2Hs)(OCH2-morpholin-4-yl) IAa.720 Cl _p(=o)(l~2-phenylen~Ai~yy) IAa.721 C~ _p(=o)(o-cH2-cH2-o) IAa.722 Cl -P(=O)[O-CH(CH3)-CH2-O]
40 IAa.723 Cl -P(=O)[O-CH(CHO-CH(CH3)-O]
IAa.724 Cl -P(=O)[O-CH(COOC~O-CH(COOCH3)-O]
IAa.725 Cl -P(=O)(O-CH2-CH2-cH2-O) IAa.726 Cl -P(=O)[O-CH2-C(CH3)2-cH2-O]
45 IAa.727 Cl -P(=o)(o-cH2-cH2-cH2-cH2-o) IAa.728 Cl -P(=S)(OH~2 IAa.729 C~ -P(=S)(OCH3)2 .
49 _ No. R4 --p(=yl)(y2Rl)(y3R2) IAa.730 Cl -P(=S)(OC2H5)2 IAa.731 Cl -P(=S)lO-(n-C3H7)]2 5 IAa.732 Cl ~P(=s)[o-(n-ctHs)]2 IAa.733 Cl -P(=S)(O-CE~2-CH2-CH2-O) IAa.734 Cl _p(=O)(NH2)2 IAa.735 Cl _p(=O)(NH-CH3)2 IAa.736 Cl _P(=O)LN(CH3)2]2 IAa.737 Cl ~P(=o)(NH-c2Hs)2 IAa.738 Cl _p(=~)[N(C2H5)2]2 IAa.739 Cl -P(=O)(NH-CEI2-CH=CH2)2 IAa.740 Cl -p(=O)(NH-c~2-c----CH)2 15 IAa.741 Cl -P(=O)(NH-cyclopropyl~z ~-IAa.742 Cl -p(=o)(NH-cH2-cyclopentyl~2 IAa.743 Cl ~p(=o)(NH-phenyl~2 IAa.744 Cl -P(=O)(NH-CH2-phenyl~2 20 IAa.745 Cl -P(=O)(pyrrolidin-1-yl~
IAa.746 Cl -P(=0)(2-methu~y~l,onyl~y~olidin IAa.747 Cl -P(=O)(NH-CH2-CO-OC~)2 IAa.748 Cl -P(=O)~N(CH3)-CH2-CO-OC~]2 IAa.749 Cl -P(=O)(NH-CH2-CO-OC2Hs)2 ~a.750 Cl -P(=O) N(CH3)-CH2-CO-OC2Hs 2 IAa.751 Cl -P(=O) NH-CH(CH3)-CO-OcH3: 2 IAa.752 Cl -P(=O)(OH)(NH2) IAa.753 Cl -P(=O)(OH)(NH-CEO
IAa.754 Cl _p(=O)(OH)[N~CH3)2]
,_ IAa.755 Cl _p(=o)(oH)(NH-c2Hs) - IAa.756 Cl _p(=O)(OH)tN(c2H5)2]
IAa.757 Cl --P(=O)(OH){NH-CH2-CH=CH2) 3 5 IAa.758 Cl --P(=O)(OH)(NH-CH2-C_ CH) IAa.759 Cl --P(=O)(OH)(NH-cyclopropyl) IAa.760 Cl -P(=O)(OH)(NH-C~2-cyclopentyl) IAa.761 Cl --P(=O)(OH)(NH-phenyl) 40 IAa.762 Cl -P(=O)(OH)(NH-CH2-phenyl) IAa.763 Cl -P(=O)(OH)(pyrrolidin-1-yl) IAa.764 Cl -P(=O)(OH)(2-metho~y~.l,ol.yll,yl.ùlidin-1-yl) IAa.765 Cl -P(=O)(OH)(NH-C~2-CO-OC~3) IAa.766 Cl -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
IAa.767 Cl -P(=O)(OH)(NH-CE~-CO-OC2Hs) IAa.768 Cl -p(=o)(oH)[N(cH3)-cH2-co-oc2Hs]
0050/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)~y2Rl)(y3R2) _ IAa.769 Cl -P(=O)(OH)[NH-CH(CH3)-CO-OCE~3]
IAa.770 Cl _p(=O)(OCH3)(NH2) 5 IAa.771 Cl -P(=O)(OCH3)(NH-CH3) IAa.772 Cl _p(=O)(OCH3)[N(CH3)2]
IAa.773 Cl -P(=o)(ocH3)(NH-c2Hs) IAa.774 Cl _p(=o)(OCH3)[N(C2Hs)2]
IAa.775 Cl --P(=O)(OCH3)(NH-CH2-CH=CH2) IAa.776 Cl -P(=O)(OCH3)(NH-CH2-C--CH) IAa.777 Cl -P(=O)(OCH3)(NH-cyclopropyl) IAa.778 Cl -P(=O)(OCH3)(NH-CH2-cyclopentyl) IAa.779 Cl -P(=O)(OCH3)(NH-phenyl) 15 IAa.780 Cl -P(=O)(OCH3)(NH-CH2-phenyl) f; IAa.781 Cl -P(=O)(OCH3)(pyrrolidin-1-yl) ;~ IAa.782 Cl -P(=O)(OCH3)(2-metho~ycarbo~yl~y.. ~lidin-1-yl) IAa.783 Cl -P(=O)(OCH3)~NH-CH2-CO-OCE~3) 20 IAa.784 Cl -P(=O)(OCH3)[N(CH3)-CH2-CO-OCH3]
IAa.785 Cl -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.786 Cl -p(=o)(ocH3)[N(cH3)-cH2-co-oc2Hs]
IAa.787 Cl -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
25 IAa.788 Cl -P(=O)(OC2Hs)(NH2) IAa.789 Cl -P(=o)(oc2Hs)(NH-cH3) IAa.790 Cl -P(=O)(OC2Hs)[N(cH3)2]
IAa.791 Cl -P(=o)(oc2Hs)(NH-c2H5) IAa.792 Cl _p(=o)(oc2Hs)[N(c2Hs)2]
IAa.793 Cl -p(=o)(oc2Hs)(NH-cH2-cH=cH2) IAa.794 Cl ~P(=o)(oc2Hs)(NH-cH2-c--CH) IAa.795 Cl -P(=O)(OC2Hs)(NH-cyclopropyl) IAa.796 Cl -P(=O)(OC2Hs)(NH-CH2-cyclopentyl) 3 5 IAa.797 Cl ~P(=O)(oc2Hs)(NH-phenyl) IAa.798 Cl -P(=O)(OC2Hs)(NH-CH2-phenyl) IAa.799 Cl ~P(=o)(oc2Hs)(pyrrolidin-l-yl) IAa.800 Cl -P(=O)(OC2Hs)(2-methoxycarb~ yl~,y.. olidin-1-yl) 40 IAa~801 Cl -P(=O)(OC2Hs)(NH-CH2--CO-OCH3) IAa.802 Cl -P(-O)(OC2Hs)tN(CH3)-CH2-CO-OCH3]
IAa.803 Cl -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.804 Cl -P(=O)(OC2Hs)[N(CH3)-cH2-cO-oc2H5]
45 IAa.805 Cl -P(=O)(OC2Hs)[NH-CH(CH3)-CO-OC~I3]
IAa.806 Cl --P(=O)rN(CH3)2~(OCH3) IAa.807 Cl -P(=o)tN(cH3)2](oc2H5) CA 02245659 l998-08-06 51 _ No. R4 _p(=y1)(Y2R1)(Y3R2) IAa.808 Cl _p(=O)[N(CH3)2] ~~(n~C3H7)]
IAa.809 Cl -P(=O)[N(CH3)2] OCH(CH3)2]
IAa.810 Cl _p(=O)[N(CH3)2] O-(n-ciH9)]
IAa.811 Cl -P(=O) N(cH3)2(ocH2-cH=cH2) IAa.812 Cl -P(=O) N(CH3)2(OCH2-Ce CH) IAa.813 Cl -P(=O) N(CH3)2(O-cyclohe~yl) IAa.814 Cl -P(=O) N(CH3)2(OCH2-cyclohe~yl) IAa.815 Cl -P(=O) N(CH3)2(O-phenyl) IAa.816 Cl -P(=O) N(CH3)2(OCH2-phenyl) IAa.817 Cl -P(=O)[N(CH3)2](O-tetra~y~fulan-2-yl) IAa.818 Cl -P(=O)~N(CH3)2](0CH2-o~etan-3-yl) 15 IAa.819 Cl -P(=O)LN(CH3)2](OCH2-CF3) IAa.820 Cl -P(=O)[N(CH3)2](OCH2-CO-OCH3) ~IAa.821 Cl -P(=O)[N(CH3)2](OCH2-CO-OC2Hs) IAa.822 Cl -P(=O)~NH-CH2-CH2-O) 20 IAa.823 Cl -P(=O)~NH-CH2-CH2-NH) IAa.824 Cl -P(=O)[N(CH3)-CHz-CH2-N(CH3)]
IAa.825 Cl -P(=O)~NH-CH2-CH2-CH2-O) IAa.826 Cl -P(=O)(NH-CHz-CH2-CH2-NH) 25 IAa.827 Cl -P(=O)[N(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.828 Cl -P(=O)(O-CH2-CH(CH3)-cH2-O) IAa.829 Cl -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.830 C~ -P(=O) N(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.831 Cl -P(=O)NH-CH2-CH2-CH2-cH2-O]
3 IAa.832 Cl -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.833 Cl _P(=s)~H2)2 IAa.834 Cl -P(=s)(NH-cH3)2 IAa.835 Cl -P(=S)[N(CH3)2]2 35 IAa.836 Cl -P(=S)(NH-C2Hs)2 IAa.837 Cl -P(=S)[N(C2Hs)2]2 IAa.838 Cl -P(=S)(NH-CH2-CH2-CH2-O) IAa.839 Cl -P(=S)(NH-CH~-CH2-CH2-NH) IAa840 Cl -P(=S)tN(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.841 Cl _p(=O)(SCH3)2 IAa.842 Cl ~P(=~)(SC2Hs)2 IAa.843 Cl _p(=o)[s-(n-caH7)]2 IAa.844 Cl _p(=O)[SCH(CH3)2]2 IAa.845 Cl -P(=O)~S-(n-~Hs)]2 IAa.846 Cl _p(=o)(scH2-cH=cH2)2 CA 0224~6~9 1998-08-06 No. R4 _p(=y1)(Y2Rl)(Y3R2) IAa.847 Cl -P(=O)(S-phenyl~2 L~a.848 Cl -p(=o)(scH2-phenyl~2 IAa.849 Cl -P(=o)(scH2-co-ocEO2 IAa.850 Cl -P(=O)(SCH2-CO-OC2H5)2 IAa.851 Cl -P(=O)(S-CE~2-CH2-CH2-S) IAa.852 Cl -P(=o)(s-c~2-cH2-cH2-o) IAa.853 Cl -P(=S)(SCH3)2 IAa.854 Cl -P(=S)(SC2H5)2 L~a.855 Cl -P(=S)[S-(n-C3H7)]2 IAa.856 Cl -P(=S)[S-n-C~Hs)]2 IAa.857 Cl -p(=s)(s-cEI2-cH2-cH2-s) IAa.858 Cl -P(=S)(S-CH2-CH2-CH2-O) IAa.859 F -P(=O)(OH)2 L~a.860 F -P(=O)(OcH3)2 IAa.861 F -P(=O)(Oc2H5)2 IAa.862 F -P(=O)[O-(n-C3H~)]2 IAa.863 F -P(=O)[OCH(CH3)2]2 IAa.864 F -P(=O)[O-(n-~Hg)]2 IAa.865 F -p(=o)[ocH2-cH(cH3)2 2 IAa.866 F -p(=o)[ocH(cH3)-c2Hs 2 IAa.867 F -p(=o)(ocH2-cF3)2 IAa.868 F -p(=o)(ocH2-cH2-oH~2 IAa.869 F -P(=O)(OCH2-CH2-CN~2 IAa.870 F -p(=o)(ocH2-cH2-ocH3)2 IAa.871 F -p(=o)(ocH2-cH2-oc2Hs)2 IAa.872 F -p(=o)(ocH2-cH2-ocF3)2 IAa.873 F -P(=O)(OCH2-CH2-OCH2-CH=CH2)2 IAa.874 F -P(=O)(OCH2-CH2-OCH2-C= CH)2 IAa.875 F -P(=O)(OCH2-CH2-O-cyclopentyl~2 IAa.876 F -P(=O)(OCH2-CHz-NH2)2 IAa.877 F -P(=O)(OCH2-CH2-NH-CH3)2 IAa.878 F -P(=O)[OCH2-CH2-N(CH3)2~2 IAa.879 F -p(=o)(ocH2-cH2-scH3)2 IAa.880 F -P(=O)(OCH2-CH2-SC2Hs)2 IAa.881 F -p(=o)(ocH2-cH2-scF3)2 IAa.882 F --P(=O)(OCEl2-CH2-SCH2-CH=cH2)2 IAa.883 F -P(=O)(OCE32-CH2-SC~2--C2 CH)2 IAa.884 F --P(=O)(OCH2-CH2-SO-cHB)2 IAa.885 F -p(=o)(ocH2-cH2-so-c2Hs)2 0050/46586 CA 02245659 l998-08-06 No. R4 _p(=yl)(Y2R1)(Y3R2) IAa.886 F -p(=o)(ocH2-so2-cH3)2 LAa.887 F -p(=o)(ocH2-so2-c2Hs)2 5IAa.888 F -p(=o)(ocH2-cH2-so2-cH3)2 L~a.889 F -p(=o)(ocH2-cH2-so2-c2Hs)2 IAa.890 F -p(=o)(ocH2-cH=cH2)2 IAa.891 F -p(=o)(ocH2-cH=cH-cH3)2 L~a.892 F -p(=o)(ocH2-cH2-cH=cH2)2 IAa.893 F -P(=O)(OCH2-CH=CH-Cl~2 L~a.894 F -p(=o)(ocH2-c--CH)2 IAa.895 F -P(=O)[OCH(CH3)-C--CH]2 IAa.896 F -p(=o)(ocH2-co-ocH3)2 15IAa.897 F _p(=o)(ocH2-co-oc2Hs)2 a.898 F -P(=O)[OcH(cH3)-cO-OcH3]2 IAa.899 F -P(=O)[OCH(CH3)-CO-OC2Hs]2 IAa.900 F -p(=o)(ocH2-co-N~2)2 20L~a.901 F -p(=o)(ocH2-co-NH-cH3)2 IAa.902 F -P(=O) OcH2-co-N(cH3)2]2 IAa.903 F -P(=O) OCH(CH3)-CO-N~2]2 IAa.904 F -P(=O)-OCH(CH3)-CO-NH-CH3]2 25IAa.905 F -P(=O) OCH(CH3)-CO-N(CH3)2]2 IAa.906 F -P(=O)(O-cyclopropyl~
L9a.907 F -P(=O)(O-cyclobutyl~Q
IAa.908 F -P(=O)(O-~;y~lOp~lllyl~2 IAa.909 F --P(=O)(O--cyclohe~cyl~2 IAa.910 F -P(=O)(OCH2-cyclopropyl)2 a.911 F -P(=O)(OCE~2-cyclobutyl)2 IAa.912 F -P(=O)(OCH2-cyclopent-yl)2 IAa.913 F -P(=O)(OCH2-cyclohexylh 35 IAa.914 F -P(=O)(O-phenyl~
IAa.915 F -P(=O)(OCH2-phenylh IAa.916 F -P(=O)(O-oxetan-3-yl~
IAa.917 F -P(=O)(O-tetrahydlorul~-2-yl~
40 IAa.918 F -P(=O)(O-tetrahydrofuran-3-yl~
IAa.919 F --P(=O)(O-tetraLydlo~,ylan-2--yl~
IAa.920 F -P(=O)(O-tetrahy&o~yld.~-3--yl~
IAa.921 F --P(=O)(O-tetrallydlol,ylail-4 IAa.922 F -P(=O)(OCHz-oxiran-2-yl~2 -IAa.923 F -P(=O)(OCH2-oxetan-3-ylk IAa.924 F -P(=O)(OCH2-tetrahydlorulan-2-yl~
.
54 _.
No. R4 --p(=y1)(Y2R1)(Y3R2) IAa.925 F -P(=O)(OCH2-tetrally&oru,an-3-yl~
IAa.926 F -P(=O)(OCH2-pyrrolidin-l-yl~
IAa.927 F -P(=O)[OCH2-(2-pyrrolidon-1-yl)~
IAa.928 F -P(=O)(OCHz-tetral y~l~o~y~-2-yl~
IAa.929 F -P(=O)(OCH2-tetrahy&~ylan--3-yl~
LAa.930 F -P(=O)(OCH2-tetrahy dl c~y ~ an-4-yl~
IAa.931 F -p(=o)(ocH2-riren~lin-l-yl~?
IAa.932 F -P(=O)(OCH2-morpholin-4-yl~
IAa.933 F -P(=O)(OH)(OCH3) L~a.934 F -p(=o)(oH)(oc2Hs) IAa.935 F -P(=O)(OH) O-[n-C3H7)]
LAa.936 F -P(=O)(OH) OCH(CH3)2]
IAa.937 F -P(=O)(OH) O-(n-CiHg)]
IAa.938 F -P(=O)(OH) OcH2-cH(cH3)2 IAa.939 F -P(=O)(OH) ocH(cH3)-c2Hs IAa.940 F -P(=O)(OH)(OCH2-CF3) IAa.941 F -P(=O)(OH)(OCH2-CH2-OH) IAa.942 F -P(=O)(OH)(OCH2-CH2-CN) IAa.943 F -P(=O)(OH)(OCH2-CH2-OCH3) IAa.944 F -p(=o)(oH)(ocH2-cH2-oc2Hs) IAa.945 F -P(=O)(OH)(OCH2-CH2-OCF3) IAa.946 F -P(=O)(OH)(OCH2-CH2-OCH2-CH=CH2) IAa.947 F -P(=O)(OH)(OCH2-CH2-OCH2-C--CH) IAa.948 F -P(=O)(OH)(OCH2-CH2-O-cyclopentyl) IAa.949 F -P(=O)(OH)(OCH2-CH2-NH2) IAa.950 F -P(=O)(OH)(OCH2-CH2-NH-CH3) -_ IAa.951 F -P(=O)(OH)tOCH2-CH2-N(CH3)2]
IAa.952 F -P(=O)(OH)(OCH2-CH2-SCH3) 3 5 IAa.953 F --P(=O)(OH)(OCH2-CH2-Sc2Hs) IAa.954 F -P(=O)(OH)(OCH2-CH2-SCF3) IAa.9SS F -P(=O)(OH)(OCH2-CH2-SCH2-CH=CH2) IAa.956 F -P(=O)(OH)(OCH2-CH2-SCH2-C----CH) IAa 957 F -P(=O)(OH)(OCH2--CH2-SO--CH3) IAa.958 F -P(=O)(OH)(OCH2-CH2-SO-C2H~) IAa.9S9 F --P(=O)(OH)(OCH2-SO2-CH3) IAa.960 F -p(=o)(oH)(ocH2-so2-c2Hs) IAa.961 F -P(=O)(OH)(OCH2--CH2--SO2--CH3) IAa.962 F -P(=O)(OH)(OCH2-CH2-SO2-C2Hs) IAa.963 F -p(=o)(oH)(ocH2-cH=cH2) OOSO/46586 CA 0224~6~9 l998-08-06 .
No. R4 _p(=yl)(y2Rl)(y3R2) IAa.964 F -P(=O)(OH)(OCH2-CH=CH-C~) IAa.965 F -p(=o)(oH)(ocH2-cH2-cH=cH2) 5 IAa.966 F -P(=O)(OH)(OCH2-CH=CH-Cl) IAa.967 F -P(=O)(OH)(OCH2-C= C~I) IAa.968 F -P(=O)(OH)[OCH(CH3)-C--CH
IAa.969 F -P(=O)(OH)(OCH2-CO-OCH3) IAa.970 F -P(=O)(OH)(OCH2-CO-OC2Hs) IAa.971 F -P(=O)(OH) OCH(CH3)-CO-OCH3]
IAa.972 F -P(=O)(OH) OCH(CH3)-CO-OC2H5]
IAa.973 F -P(=O)(OH)(OCH2-CO-NEI2) IAa.974 F -P(=O)(OH)(OCH2-CO-NH-CEO
15 IAa.975 F -P(=O)(OH)[OcH2-cO-N(c~3)2]
-- IAa.976 F -p(=o)(oH)[ocH(cH3)-co-NEI2]
IAa.977 F -P(=O)(OH)[OCH(CH3)-CO-NH-C~]
IAa.978 F -P(=O)(OH)[OCH(CH3)-CO-N(C~3)2]
20 IAa.979 F -P(=O)(OH)(O-cyclopropyl) IAa.980 F -P(=O)(OH)(O-cyclobutyl) IAa.981 F -P(=O)(OH)(O-cyclopentyl) IAa.982 F -p(=o)(oH)(o-cyclohe~cyl) 25 IAa.983 F -P(=O)(OH)(OCH2-cyclopropyl) IAa.984 F -P(=O)(OH)(OCH2-cyclobutyl) IAa.985 F -P(=O)(OH)(OCH2-cycloye ~ ~ Iyl) IAa.986 F -P(=O)(OH)(OCH2-cyclohexyl) IAa.987 F -P(=O)(OH)(O--phenyl) IAa.988 F -P(=O)(OH)(OCH2-phenyl) ~,IAa.989 F --P(=O)(OH)(O-o~etan--3--yl) -IAa.990 F -P(=O)(OH)(O-tetrahy~Lvr~lla~.-2-yl) IAa.991 F -P(=O)(OH)(O-tetrahyd-orulall-3-yl) 35 IAa.992 F -P(=O)(OH)(O-tetrahyLo~y~all-2-yl) IAa.993 F -P(=O)(OH)(O--tetraLy~Ilol,ylall-3-yl) IAa.994 F -P(=O)(OH)(O-tetrahy~Lo~ylan-4-yl) IAa.995 F -P(=O)(OH)(OCH2-oxiran-2-yl) 40 IAa~996 F -P(=O)(OH)(OCH2-o~etan-3-yl) IAa.997 F -P(=O)(OH)(OCH2-tetral~ydlorulau--2--yl) IAa.998 F -P(=O)(OH)(OCH2-tetral-ydlc,Lulail-3-yl) IAa.999 F -P(=O)(OH)(OCH2-pyrrolidin-1-yl) 45 IAa.1000 F -P(=O)(OH)[OCH2-(2-pyrrolidon-1-yl)]
IAa.1001 F --P(=O)(OH)(OCH2--tetrallydl~ylan--2--yl) IAa.1002 F -P(=O)(OH)(OCH2-tetral.ydlo~,ylan-3-yl) 0050/46586 CA 0224~6~9 19s8-08-06 .
56 _ No. R4 -P(=yl)~y2Rl)~y3R2) IAa.1003 F -P(=O)(OH)(OCH2-tetra~y~o~.an-4-yl) IAa.1004 F -P(=O)(OH9(0CH2-pipendin-1-yl) 5 IAa.lOU5 F -P(=O)(OH)(OCH2-morpholin-4-yl) IAa.1006 F -P(=O)(OCH3)(OC2Hs) IAa.1007 F -P(=O)(OCH3)[O-(n-C3H7)]
L~a.1008 F -P(=O)(OCH3)[0CH(CH3)2]
IAa.1009 F - P(=O)(OCH3) O-(n-C~Hg)]
~Aa.1010 F --P(=O)(OCH3) 0CH2-CH(CH3)2]
IAa.1011 F -P(=O)(OCH3) OCH(CH3)-C2Hs]
IAa.1012 F -P(=O)(OCH3)(OCH2-CF3) IAa.1013 F -P(=O)(OCH3)(OCH2-CH2-OH) 15 IAa.lO14 F -P(=O)(OCH3)(0CH2-CH2-CN~
~IAa.1015 F -P(=O)(OCH3)(OCH2-CH2-OCH3) ~-IAa.1016 F -P(=O)(OCH3)(OCH2-CH2-OC2Hs) IAa.1017 F -P(=O)(OCH3)(OCH2-CH2-OCF3) 20 LAa.1018 F -P(=O)(OCH3)(OCH2-CH2-OCH2-CH=CH2) IAa.1019 F -P(=O)(OCH3)(OCH2-CH2-OCH2-C-- CH) IAa.1020 F -P(=O)(OCH3)(OCH2-CH2-O-cyclopentyl) IAa.1021 F -P(=O)(OCH3)(0CH2-CH2-NH2) 25 IAa.1022 F -P(=O)(OCH3)(OCH2-CH2-NH-CH3) IAa.1023 F -P(=O)(OCH3)[0CH2-CH2-N(CH3)2]
IAa.1024 F -P(=O)(OCH3)(OCH2-CH2-SCH3) IAa.1025 F -P(=O)(OCH3)(OCH2-CH2-SC2Hs) IAa.1026 F -P(=O)(OCH3)(OCH2-CH2-SCF3) ~ IAa.1027 F -P(=O)(OCH3)(0CH2-CH2-SCH2-CH=CH2) IAa.1028 F -P(=O)(OCH3)(0CH2-CH~-SCH2--C--CH) LAa.1029 F -P(=O)(OCH3)(0CH2-CH2-SO-CH3) IAa.1030 F -P(=O)(OCH3)(OCH2-CH2-SO-C2Hs) 35 IAa.1031 F -P(=O)(OCH3)(OCH2-SO2-CH3) IAa.1032 F -P(=O)(OCH3)(OCH2-SO2-C2Hs) IAa.1033 F -P(=O)(OCH3)(OCH2-CH2-SO2-CH3) IAa.1034 F -P(=O)(OCH3)(OCH2-CH2-SO2-C2Hs) 40 IAa.1035 F -P(=O)(OCH3)(OCH2-CH=CH2) IAa.1036 F -P(=O)(OCH3)(OCH2-CH=CH-CH3) IAa.1037 F -P(=O)(OCH3)(OCH2-CH2-CH=CH2) IAa.1038 F -P(=O)(OCH3)(OCH2-CH=CH-Cl) IAa.1039 F -P(=O)(OCH3)(OCH2-C- CH) IAa.1040 F -P(=O)(OCH3)[0CH(CH3)-C_ CH~
IAa.1041 F -P(=O)(OCH3)(OCH2-CO-OCH3) 57 _ No. R4 _p(=yl)(y2Rl)(y3Rz) IAa.1042 F -P(=O)(OCH3)(OCH2-CO-OC2Hs) IAa.1043 F -P(=O)(OCH3) OCH(CH3)-CO-OCH3]
5 IAa.1044 F -P(=O)(OCH3) OCH(CH3)-CO-OC2Hs]
IAa.1045 F -p(=o)(ocH3)(ocH2-co-N~2) IAa.1046 F -P(=O)(OCH3)(OCH2-CO-NH-C~) IAa.1047 F -P(=O)(OCH3)[OCH2-CO-N(CH3)2]
IAa.1048 F -P(=O)(OCH3)[0CH(CH3)-CO-N~2]
IAa.1049 F -P(=O)(OCH3)[0CH(CH3)-CO-NH-C~;]
IAa.1050 F -P(=O)(OCH3)[0CH(CH3)-CO-N(CH3)2]
IAa.1051 F -P(=O)(OCH3)(O-cyclopropyl) IAa.1052 F -P(=O)(OCH3)(0-cyclobutyl) lS IAa.1053 F -P(=O)(OCH3)(0-cyclopentyl) IAa.1054 F -P(=O)(OCH3)(O-cyclohexyl) IAa.1055 F -p(=o)(ocH3)(ocH2-~;yolo~o~yl) IAa.1056 F -P(=O)(OCH3)(0CH2-cyclobutyl) 20 IAa.1057 F -P(=O)(OCH3)(OCH2-cyclopentyl) IAa.1058 F -P(=O)(OCH3)(OCH2-cyclohexyl) IAa.1059 F -P(=O)(OCH3)(O-phenyl) IAa.106Q F -P(=O~(OCH~(OCH2-phenyl) 25 IAa.1061 F -P(=O)(OCH3)(0-oxetan-3-yl) IAa.1062 F -P(=O)(OCH3)(0-tetrally&~.rul~-2-yl) IAa.1063 F -P(=O)(OCH3)(O-tetrahy-l.orulc,n-3-yl) L~a.1064 F -P(=O)(OCH3)(O-tetrally&u~y,an-2-yl) IAa.1065 F -P(=O)(OCH3)(O-tetrahy~Lo~y.a.l-3-yl) IAa.1066 F -P(=O)(OCH3)(O-tetral,y-l.u~,y.dn-4-yl) IAa.1067 F -P(=O)(OCH3)(OCH2-oxiran-2-yl) f' IAa.1068 F -P(=O)(OCH3)(0CH2-oxetan-3-yl) IAa.1069 F -P(=O)(OCH3)(OCH2-tetral~yd~uru~ -2-yl) 35 IAa.1070 F --P(=O)(OCH3)(0CH2-tetrahydrofuran-3-yl) IAa.1071 F -P(=O)(OCH3)(0CII~ ~y~ulidin-1-yl) IAa.1072 F -P(=O)(OCH3)tOCH2-(2-pyrrolidon-1-yl)]
IAa.1073 F -P(=O)(OCH3)(OCH2-tetrahy~llu~ylan-2-yl) 40 IAa.1074 F -P(=O)(OCH3)(OCH2-tetraLydlo~y~-3-yl) IAa.1075 F -P(=O)(OCH3)(OCH2-tetrahy-l.u~y.dn-4-yl) IAa.1076 F -P(=O)(OCH3)(OCH2-piperi(lin-1-yl) IAa.1077 F -P(=O)(OCH3)(OCH2-morpholin-4-yl) 45 IAa.1078 F --P(=O)(OC2Hs)[O-(n-C3H7)]
L~a.1079 F -p(=o)(oc2Hs)[ocH(cH3)2]
IAa.1080 F --P(=O)(OC2Hs)[O-(n-ciH9)]
0050/46586 CA 0224~6~9 1998-o8-b6 No. R4 _p(=yl)cy2Rl)cy3R2) I~a.1081 F --P(=O)(OC2Hs)[OCH2-CH(CH3)2]
LAa.1082 F -p(=o)(oc2H5)[ocH(cH3)-c2H5]
5LAa.1083 F -P(=O)(OC2H5)(0CH2-CF3) LAa.1084 F -P(=O)(OC2H5)(0CH2-CH2-OH) LAa.1085 F -P(=O)(OC2H5)(0CH2-CH2-CN) I~a.1086 F -P(=O)(OC2H5)(0CH2-CH2-OCH3) LAa.1087 F -P(=O)(OC2H5)(0CH2-CH2-OC2H5) I~a.1088 F -P(=O)(OC2H5)(0CH2-CH2-OCF3) LAa.1089 F -p(=o)(oc2H5)(ocH2-cH2-ocH2-cH=cH2) I~a.1090 F -P(=O)(OC2H5)(0CH2-CH2-OCH2-C3 CH) I~a.1091 F -P(=O)(OC2H5)(0CH2-CH2-O-cyclopentyl) 15LAa.1092 F -p(=o)(oc2H5)(ocH2-cH2-NH2) a.1093 F -P(=O)(OC2H5)(0CH2-CH2-NH-CH3) LAa.1094 F -p(=o)(oc2H5)[ocH2-cH2-N(cH3)2]
LAa.1095 F -P(=O)(OC2H5)(OCH2-CH2-SCH3) 20LAa.1096 F -P(=O)(OC2Hs)(OCH2-CH2-SC2H5) LAa.1097 F -P(=O)(OC2H5)(0CH2-CH2-SCF3) LAa.1098 F -P(=O)(OC2Hs)(OCH2-CH2-SCH2-CH=CH2) LAa.1099 F -P(=O)(OC2H5)(0CH2-CH2-SCH2-C2 CH) 25LAa.llO0 F -P(=O)(OC2H5)(0CH2-CH2-SO-CH3) LAa.llOl F -P(=O)(OC2H5)(0CH2-CH2-SO-C2H5) LAa.1102 F --P(=O)(OC2H5)(OCH2-SOz-CH3) LAa.1103 F --P(=O)(OC2H5)(0CH2--S02--C2H5) LAa.1104 F -P(=O)(OC2H5)(0CH2-CH2-SO2-CH3) I~a.1105 F -P(=O)(OC2H5)(0CH2-CH2-SO2-C2H5) a.1106 F --P(=O)(OC2H5)(0CH2-CH=CH2) LAa.1107 F -P(=O)(OC2H5)(0CH2-CH=CH-CH3) LAa.1108 F -p(=o)(oc2H5)(ocH2-cH2-cH=cH2) 35I~a.llO9 F -P(=O)(OC2H5)(0CH2-CH=CH-Cl) LAa.lllO F -P(=O)(OC2H5)(0CH2-C2 CH) I~a.llll F --P(=O)(OC2H5)[OCH(CH3)--C--CH]
I~a.1112 F -P(=O)(OC2Hs)(OCH2-CO-OCH3) 40LAa.1113 F -P(=O)(OC2H5)(0CH2-CO-OC2H5) I~.1114 F - P(=O)(OC2H5)[OCH(CH3) - CO - OCH3]
a.1115 F -P(=O)(OC2H5)[0CH(CH3)-CO-OC2H5]
I~.1116 F -P(=O)(OC2H5)(OCH2-CO-N~2) 45I~.1117 F -P(=O)(OC2H5)(OCH2-CO-NH-CH~) I~a.1118 F -p(=o)(oc2H5)[ocH2-co-N(cH3)2]
LAa.lll9 F -p(=o)(oc2H5)[ocH(cH3)-co-NH2]
0050/46586 CA 0224~6~9 l998-08-06 .
.
59 . _ No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1120 F ~P(=o)(oc2Hs)[ocH(cH3)-co-NH
IAa.1121 F -P(=O)(OC2Hs)[ocH(cH3)-co-N(cH3)2 5 IAa.1122 F -P(=O)(OC2Hs)(O-cyclopropyl) IAa.1123 F -P(=O)(OC2Hs)(O-cyclobutyl) IAa.1124 F -P(=O)(OC2Hs)(O-cydopentyl) IAa.1125 F -P(=O)(OC2Hs)(O-cy-clohe~yl) IAa.1126 F -P(=O)(OC2Hs)(OCH2-cyclopropyl) IAa.1127 F -P(=O)(OC2Hs)(OCH2-cyclobutyl) IAa.1128 F -P(=O)(OC2Hs)(OCH2-cyclopentyl) IAa.1129 F --P(=O)(OC2Hs)(OCH2-cyclohexyl) IAa.1130 F _p(=o)(oC2Hs)(O-PhenYl) 15 IAa~ll3l F ~P(=o)(oc2Hs)(ocH2-phenyl) -IAa.1132 F -P(=O)(OC2Hs)(O-oxetan-3-yl) IAa.1133 F --P(=~)(~C2Hs)(O-tetral y& uru. an-2-yl) IAa.1134 F ~p(=o)(oc2Hs)(o-tetrahy&~lfuldll-3-yl) 20 IAa.1135 F ~P(=~)(~C2Hs)(O-tetrahydlo~,y.an-2-yl) IAa.1136 F ~p(=o)(oc2Hs)(o-tetrahyd~o~y~an-3-yl) IAa.1137 F ~P(=~)(~C2Hs)(O-tetrahydlo~,y~all~-yl) IAa.1138 F -P(=O)(OC2Hs)(OCH2-oxiran-2-yl) 25 IAa.1139 F -P(=O)(OC2Hs)(OCH2-o~etan-3-yl) IAa.1140 F --P(=O)(OC2Hs)(OCH2-tetrahydrofuran-2-yl) IAa.1141 F -P(=O)(OC2Hs)(OCH2-tet~ahy~l.oru.a~l-3-yl) IAa.1142 F --P(=O)(OC2Hs)(OCH2-pyrrolidin-l--yl) IAa.1143 F -P(=O)(OC2Hs)[OCH2-(2-pyrrolidon-l-yl)]
LAa.1144 F -P(=O)(OC2Hs)(OCH2-tetrahyd.. ,~ylail-2-yl) __ IAa.1145 F -P(=O)(OC2Hs)(OCH2-tetrahydlopy.àil-3-yl) IAa.1146 F -P(=O)(OC2Hs)(OCH2-tetrahyd.o~ylan-4-yl) IAa.1147 F --P(=O)(OC2Hs)(OCH2--pip~ori(1in--l--yl) IAa.1148 F -P(=O)(OC2Hs)(OCH2-morpholin-4-yl) IAa.1149 F --P(=0)(1,2--phenylenf~iioxy) IAa.1150 F -P(=O)(O-CEI2-CH2-O) IAa.llSl F -P(=O) O-CH(CH3)-CH2-O]
40 IAa.llS2 F -P(=O) Q-CH(CH3)-CH(CH3)-O]
IAa.1153 F -P(=O) O-CH(COOCH3)-CH(COOCH3)-O]
IAa.1154 F _P(=o)(o-c~2-cH2-cH2-o) IAa.llSS F -P(=O)[O-CE~2-C(CH3)2-CH2-O]
45 IAa.1156 F -P(=O)(O-C~2-CH2-CH2-CH2-O) - IAa.1157 F -P(=S)(OH~2 IAa.1158 F -P(=S)(OCH3)2 0050/46586 CA 02245659 l998-08-06 No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1159 F -p(=s)(oc2Hs)2 IAa.1160 F -P(=S) o-(n-c3H7)]2 5 IAa.1161 F -P(=S) o-(n-clHs)]2 IAa.1162 F -p(=s)(o-c~2-cH2-cH2-o) IAa.1163 F -P(=O)(NH2)2 IAa.1164 F -P(=O)(NH-CH~)2 IAa.1165 F -P(=O)tN(CH3)2]2 IAa.1166 F -p(=o)(NH-c2Hs)2 IAa.1167 F -P(=O)[N(C2Hs)2]2 IAa.1168 F -p(=o)(NH-cH2-cH=cH2)2 IAa.1169 F -P(=O)(NH-CE~2-C--CH)2 15 IAa.1170 F -P(=O)~H-~iydo~lu,uYl~e fIAa.1171 F -P(=O)(NH-CEI2-cyclopentyl~2 IAa.1172 F -P(=O)(NH-phenyl~z IAa.1173 F -p(=o)(NH-cH2-phenyl~2 - 20 IAa.1174 F -P(=O)(pyrrolidin-1-yl~
IAa.1175 F -P(=0)(2-methoxycarbc,~yl~y,.~,lidin-1-yl~
IAa.1176 F -P(=O)(NH-CH2-CO-OCH3)2 IAa.1177 F -P(=O)[N(CH3)-CH2-CO-OC~3]2 25 IAa.1178 F -P(=O)(NH-CE~2-CO-OC2Hs)2 IAa.1179 F -p(=o)[N(cH3)-cH2-co-oc2Hs]2 IAa.1180 F -P(=O)tNH-CH(CH3)-cO-Oc~3]2 IAa.1181 F --P(=O)(OH)(NH2) IAa.1182 F -P(=O)(OH)(NH-CHB) IAa.1183 F -P(=O)(OH)[N(CH3)2]
IAa.1184 F -P(=O)(OH)(NH-C2H5) _ IAa.1185 F -P(=O)(OH)tN(C2Hs)2]
IAa.1186 F -P(=O)(OH)(NH-CH2-CH=CH2) 35 IAa.1187 F -P(=O)(OH)(NH-CK2-C--CH) IAa.1188 F -P(=O)(OH)(NH-cyclopropyl) IAa.1189 F -P(=O)(OH)(NH-CH2-cydopentyl) IAa.1190 F -P(=O)(OH)(NH-phenyl) 40 IAa.l191 F -P(=O)(OH)(NH-CH2-phenyl) IAa.1192 F --P(=O)(OH)(pyrrolidin--1-yl) IAa.1193 F -P(=O)(OH)(2-methu~y~bol-yl~y.. (Jlidin-1-yl) IAa.1194 F -p(=o)(oH)(NH-cH2-co-ocH3) IAa.1195 F -P(=O)(OH)[N(CH3)-CH2-CO-OCH3]
IAa.1196 F -P(=O)(OH)(NH-CK2-CO-OC2Hs) IAa.1197 F -P(=O)(OH)[N(CH3)-CH2-CO-OC2Hs]
0050/46586 CA 0224~6~9 l998-08-06 No. R4 _p(=y1)(y2Rl)(y3R2) IAa.1198 F -P(=O)(O~[NH-CH(CH3)-CO-OCH3]
IAa.1199 F -P(=O)(OCH3)(NH2) IAa.1200 F -P(=O)(OCH3)(NH-CH3) IAa.1201 F -P(=O)(OCH3)[N(CH3)2~
IAa.1202 F -P(=O)(OCH3)(NH--C2Hs) IAa.1203 F -P(=O)(OCH3)[N(C2Hs)2]
IAa.1204 F -P(=O)(OCH3)(NH-CH2-CH=CH2) IAa.1205 F -P(=O)(OCH3)(NH-CH2-C--CH) IAa.1206 F -P(=O)(OCH3)(NH-cydopropyl) IAa.1207 F -P(=O)(OCH3)(NH-CH2-cyclopentyl) IAa.1208 F -P(=O)(OCH3)(NH-phenyl) IAa.1209 F -P(=O)(OCH3)(NH-CH2-phenyl) - IAa.1210 F -P(=O)(OCH3)(pyrrolidin-1-yl) ~-IAa.1211 F -P(=O)(OCH3)(2-metho~y~-ln,--yl~y.. olidin-1-yl) IAa.1212 F -P(=O)(OCH3)~NH-CH2-CO-OCH3) IAa.1213 F -p(=o)(ocH3)[N(cH3)-cH2-co-ocH3]
IAa.1214 F -P(=O)(OCH3)(NH-CH2-CO-OC2Hs) IAa.1215 F -P(=O)(OCH3)[N(CH3)-CH2-CO-OC2Hs]
IAa.1216 F -P(=O)(OCH3)[NH-CH(CH3)-CO-OCH3]
IAa.1217 F -p(=o)(oc2Hs)(NH2) IAa.1218 F -P(=O)(OC2Hs)(NH--CH3) IAa.1219 F -p(=o)(oc2Hs)[N(cH3)2]
IAa.1220 F -P(=O)(OC2Hs)(NH-C2HS) IAa.1221 F -p(=o)(oc2Hs)tN(c2Hs)2]
IAa.1222 F -p(=o)(oc2Hs)(NH-cH2-cH=cH2) IAa.1223 F -P(=o)(oc2Hs)(NH-cH2-c--CH) LAa.1224 F -P(=O)(OC2Hs)(NH-cyclopropyl) IAa.1225 F -P(=O)(OC2Hs)(NH-CH2-cyclopentyl) IAa.1226 F -P(=O)(OC2Hs)(NH-phenyl) IAa.1227 F -P(=O)(OC2Hs)(NH--CH2--phenyl) IAa.1228 F -P(=O)(OC2Hs)(pyrrolidin-1-yl) IAa.1229 F -P(=O)(OC2Hs)(2-metho~y~all~G.. yl~Jyl.olidin-1-yl) IAa.1230 F -P(=O)(OC2Hs)(NH-CH2-CO-OCH3) IAa.1231 F -P(=O)(OC2Hs)[N(CH3)--CH2-CO-OCE~3]
L~a.1232 F -P(=O)(OC2Hs)(NH-CH2-CO-OC2Hs) IAa.1233 F -P(=O)(OC2HS) N(CH3)-CH2-CO-OC2Hs]
IAa.1234 F -P(=O)(OC2Hs) NH-CH(CH3)-CO-OCH3]
IAa.1235 F -P(=O) N(CH3)2 (OCH3) IAa.1236 F -P(=O)rN(CH3)z (OC2Hs) ~ 0050/46586 CA 02245659 l998-08-06 ~ .
No. R4 _p(=yl)(Y2Rl)(Y3R2) IAa.1237 F ~P(=o)tN(cH3)2][o-(n-c3H7)]
LAa.1238 F -p(=o)tN(cH3)2] OCH(CH3)2]
5 IAa.l239 F -P(=o)[N(cH3)2l O-(n-C1Hs)]
IAa.1240 F -p(=o)tN(cH3)2(oCH2-cH=cH2) IAa.1241 F -P(=O)tN(CH3)2(OCH2-C-- CH~
IAa.1242 F -P(=O) N(CH3)2](O-cyclohe~yl) IAa.1243 F -P(=O) N(CH3)2](OCH2-cyclohe~yl) 1IAa.1244 F -P(=O) N(CH3)2](O-phenyl) IAa.1245 F -P(=o)[N(cH3)2](ocH2-phenyl) IAa.1246 F -P(=O) N(CH3)2(0-tetra~y~vru~o~-2-yl) IAa.1247 F -P(=O) N(CH3)i(OCH2-oxetan-3-yl) 15 IAa.l248 F -P(=O)-N(CH3)2(OCH2-CF3) -IAa.1249 F -P(=O)tN(CH3)2(OCH2-CO-OC~3) ~~~ IAa.1250 F -P(=O)[N(CH3)2(OCH2-CO-OC2Hs) IAa.1251 F -P(=O)~NH-C~2-CH2-O) 20 IAa.1252 F -P(=O)~NH-CH2-CH2-NH~
IAa.1253 F -P(=O)tN(CH3)-CH2-CH2-N(CH3)]
IAa.1254 F -p(=o)(NH-cH2-cH2-cH2-o) IAa.1255 F -P(=O)~NH-CH2-CH2-CH2-NH9 25 IAa.1256 F -P(=O)tN(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.1257 F -p(=o)(o-cH2-cH(cH3)-cH2-o) IAa.1258 F -P(=O)[NH-CH2-CH2-CH2-N(CH3)]
IAa.1259 F -P(=O)tN(CH3)-CH2-C(CH3)2-CH2-N(CH3)]
IAa.1260 F -P(=O) NH-CH2-CH2-CH2-CH2-O]
lAa.1261 F -P(=O) NH-CH2-CH2-CH2-CH2-NH]
IAa.1262 F -P(=S)~NH2)2 IAa.1263 F -P(=S)(NH-CH3)2 IAa.1264 F -P(=S)tN(CH3)2]2 35 IAa.1265 F -P(=S)(NH-C2H5)2 IAa.1266 F -P(=S)[N(C2H5)2]2 IAa.1267 F -P(=S)~NH-CH2-CH2-CH2-O) IAa.1268 F -P(=S)~NH-CH2-CH2-CH2-NH~
40 IAa.l269 F -P(--S)[N(CH3)-CH2-CH2-CH2-N(CH3)]
IAa.1270 F -P(=O)(SCH3)2 IAa.1271 F -p(=o)(sc2Hs)2 IAa.1272 F -P(=O)S-(n-C3H7)2 45 IAa.1273 F -P(=O) SCH(CH3)2 2 IAa.1274 F -p(=o)s-(n-~H9)l2 IAa.1275 F -p(=o)(scH2-cH=cH2)2 OOSO/46586 CA 02245659 l998-08-06 ~, . . . .
No. R4 -P(=yl)cyzRl)cy3R2) I~.1276 F -P(=O)(S-phenyl~
L~a.1277 F -P(=O)(SC~H2-phenyl~
5 LAa.1278 F -p(=o)(sc~H2-co-oc~)2 I~.1279 F -P(=O)(SC~H2-CO-OC2Hs)2 LAa.1280 F -P(=O)(S-C~H~-C~H~-C~H2-S) LA~.1281 F -P(=o)(s-c~H~ H2-c~H2-o) I~.1282 F -P(=S)(SC~H3)2 LAa.1283 F -P(=S)(SC2Hs)2 IAa.1284 F -p(=s)[s-(n-c~H7)]2 LAa.1285 ~ -P(=S)~S-n-CiHs)]2 LA a.1286 P -P(=S)(S--C~H~--C~H2-C~H2-S) LAa.1287 F -P(=S)(S-C~H~-C~H2-C~2-O) Further especially preferred aromatic phosphonic acid derivatives are those of the form~ e IAb-IAn, IBa-IBn, ICa-ICn, IDa-IDn, 20 IEa-IEn, IFa-IFn, IGa-IGn, IHa-IHn, IKa-IKn, ILa-ILn, IMa-IMn and INa-INn, in particular - the compounds IAb~l - IAb.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is 25 --CH2--CH(Cl)--:
~ N
~ ~cO
~ N Cl ~-1 IAb (~ R ~ CH2 - CH ~ _ y Cl y3R2 - the compounds IAc.l - IAc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)-:
~-N
~/ )=O
~ N Br --1 IAc R4 ~ CH2 CH ~ - Y2R
Cl y3R2 ~ ~ 64 - the compounds IAd.1 - IAd.1287~ which differ from the corres-ponding c~ _unds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CN)-:
~ N
~ )=o 10~ ~ CN -l IAd Cl y3R2 - the c~~ ,~unds IAe.1 - IAe.1287, which differ from the corres-;~ ponding compounds IAa.1 - IAa.1287 only in that Eth is -cH2-cH(c~3)-:
~ ~~
25R4 ~ CH2 C~ y2Rl IAe C 1 y3R2 30 - the compounds IAf.1 - IAf.1287, which differ from the corres-ponding c~...~o~nds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)-:
~ N OCH3 ~_ ~~
//~ CH2 CH--~--y2Rl IAf ~
Cl y3R2 - the compounds IAg.1 - IAg.1287~ which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethenediyl:
0050/46586 CA 02245659 l998-08-06 ~ . . . .
_ N
~/ )cO
~N yl IAg R4~CH--CH . --Y2R
Cl y3R2 - the compounds IAh.1 - IAh.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C ( Cl )--:
C ' ~ ~= o ZO ~ ~3 C~ = C--'--Y~R
Cl y3R2 - the col.l~ounds IAi.1 - IAi.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Br)-:
f~ ~N
~N Br ~,1 IAi ~ ~ CH - l ~ Y2Rl Cl y3R2 40 - the compounds IAj.1 - IAj.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)-:
~N
k ~ CN .rl IAj R~.... ~CH = C ~ y2Rl Cl y3R2 - the compounds IAk.1 - IAk.1287, which differ from the corres-ponding co~uunds IAa.1 - IAa.1287 only in that Eth is 15 --CH=C (CH3 )--:
,.~ . F3C ~CH3 ~ N
R4~CEI= C --~--Y~Rl IAk C 1 y3R2 - the compounds IAm.1 - IAm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C ( COOCH3 )--:
,~ N OCH3 ~,' ~ ~0 ~ ~ CO yl IAm R4~CH C--. '_y2Rl Cl y3R2 40 - the compounds IAn.1 - IAn.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -C-C-:
0050/46586 CA 0224~659 1998-08-06 N
~ IAn R4 ~ C _ C - ~ _ y2Rl Cl y3R2 - the co-l~ounds IBa.430 - IBa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where R10 = methyl, Rl1 = difluoromethoxy and R12 - chlorine:
F2HCO Cl =~ vl ~N~ ~ IBa H3C N ~ CH2 - CH2- ' y Cl y3R2 25 - the compounds IBb.430 - IBb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)-- and R5 is the heterocycle '~I>2 where Rl~ = methyl, R11 c difluoromethoxy and Rl2 = chlorine:
F2HCO Cl C ~ C~z - C~ - I - Y2RI IBb Cl y3R2 - the compounds IBc.430 - IBc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2--CH(Br)--and R5 is the heterocycle ~2 where R10 = methyl, Rll ~ difluoromethoxy and Rl2 = chlorine:
~ , .
F2HCO Cl ~ Br yl H3C ~CH2 - CH y2Rl IBc Cl y3R2 lO - the compounds IBd.430 - IBd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where R10 = methyl, Rl1 2 difluoromethoxy and R12 = chlorine:
F2HCO ~ Cl CN yl H3C~ 'N~CH2 CH--~--y2Rl IBd Cl y3R2 - the compounds IBe.430 - IBe.1287, which differ from the corres-ponding ~,--~vunds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~2 where R10 - methyl, Rll 5 difluoromethoxy and R12 = chlorine:
F2HCO Cl --~ CH3 yl 30H3C ~ 'N~ l ll IBe R4 ~ CH2 CH P y2 -- Cl y3R2 - the compounds IBf.430 - IBf.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is - CH2 - CH ( COOCH3 ) - and R5 is the heterocycle ~2 where Rlo =
methyl, R1l = difluoromethoxy and Rl2 = chlorine:
F2HCO ~ Cl ¦ .
-N ~ CH2 C~ _ y2Rl IBf Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 69 _ - the compounds IBg.430 - IBg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~2 where R10 = methyl, R1l = difluoromethoxy and Rl2 = chlorine:
F2HCO ~ Cl ,I yl H3C ~ 'N ~ ll IBg - R4 ~ CH - CH P - Y2Rl Cl y3R2 - the compounds IBh.430 - IBh.1287, which differ from the corres-15 ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, '~ Rll = difluoromethoxy and Rl2 = chlorine:
F2HCO Cl H3C ~ - CH - C - ~ - y2Rl IBh Cl y3R2 - the compounds IBi.430 - IBi.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~2 where R10 = methyl, Rll = difluoromethoxy and Rl2 = chlorine:
F2HCO Cl f ~ Br --1 H3C N ~ CH C y2Rl IBi C 1 y3R2 40 - the compounds IBj.430 - IBj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~2 where R10 = methyl, Rll - difluoromethoxy and Rl2 = chlorine:
~, . .
F2HCO Cl CN yl ~N~N ~ CH - C P y2Rl IBj Cl y3R2 lO - the compounds IBk.430 - IBk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~2 where Rl~ = methyl, Rll s difluoromethoxy and Rl2 = chlorine:
F2HCO Cl ~ CH3 yl ,N~N' ~ CH - C - P- Y2Rl IBk Cl y3R2 ZO
- the compounds IBm.430 - IBm.1287, which differ from the corres-po~ing compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~2 where R10 ~ methyl, Rll = difluoromethoxy and Rl2 - chlorine:
FzHCO Cl ~ CO -~1 H C ~N'N ~ CH 1 P y2Rl IBm Cl y3R2 - the compounds IBn.430 - IBn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C_C-and R5 is the heterocycle ~2 where Rlo = methyl, R11 = difluoro-methoxy and Rl2 = chlorine:
~ yl ~N~N' ~ - C _ C P Y2Rl IBn Cl y3R2 0050/46586 CA 0224~6~9 l998-08-06 .
- the compounds ICa.430 - ICa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 8 chlorine:
F3C Cl ~3C ~ CH2 - C~- ~ - Y2R~ ICa Cl y3R2 - the compounds ICb.430 - ICb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, i Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl ~ Cl ~1 ~N N ~ CH2 CH - ~ - y2Rl ICb Cl y3R2 - the compounds ICc.430 - ICc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~2 where Rl~ = methyl, 30 Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl Br ~-1 ~N~N ~ CH2 CH _ y2Rl ICc \=~ ' .
Cl y3R2 40 - the compounds ICd.430 - ICd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where RlO = methyl, Rll - trifluoromethyl and Rl2 = chlorine:
CA 0224~659 1998-08-06 F3C Cl . CN yl N~N ~ CH2 CH " y2Rl ICd Cl y3R2 10 - the compounds ICe.430 - ICe.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2--CH(CH3)-- and R5 is the heterocycle ~p2 where Rl~ = methyl, Rll = trifluoromethyl and R12 2 chlorine:
15 F3C Cl CH3 yl H3C ~ ~ ~ CH2 CH P y2Rl ICe Cl y3R2 - the compounds ICf.430 - ICf.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ,~p2 where R10 =
methyl, Rll - trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl H3C'' N ~ CO yl ICf R4 ~ / \ ~ CH2--CH--P y2 ~~ ~
Cl y3R2 - the compounds ICg.430 - ICg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2--ethenediyland R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluol~ -Lhyl and Rl2 8 chlorine:
~ . .
~ 73 F3C Cl ~3,3C~ C~=C~ - P - Y~RI ICg Cl y3R2 10 - the compounds ICh430 - ICh1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is --CH=C(Cl)--and R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl Cl yl H3C N ~ CH = C P _ y2Rl ICh Cl y3R2 - the compounds ICi.430 - ICi.287, which differ from the corres-ponding c~ ounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle ~2 where Rlo = methyl, Rll = trifluoromethyl and Rl2 ~ chlorine:
F3C Cl ~ Br yl ,N~N' ~ CH - C - P y2Rl ICi t ~ Cl y3R2 - the compounds ICj.430 - ICj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ~>2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C ~ Cl CN yl , N~N~ ~ CH = C --y2Rl ICj Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 .
74 _ - the compounds ICk.430 - ICk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~2 where R10 = methyl, Rll = trifluoromethyl and Rl2 = chlorine:
F3C Cl CH3 yl N~N~CH C P- y2Rl ICk Cl y3R2 - the compounds ICm.430 - ICm.1287, which differ from the corres-ponding c~ unds IAa.430 - IAa.1287 only in that Eth is -CH=C (COOCH3 ) - and R5 is the heterocycle ~2 where R10 = methyl, ' Rll = trifluoromethyl and Rl2 - chlorine:
F3C =~ Cl CO yl ~N~N ~ CH = C - ~ y2Rl ICm Cl y3R2 - the compounds ICn.430 - ICn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~2 where R10 = methyl, R
trifluoromethyl and Rl2 3 chlorine:
.~. F3C --1=~ Cl H C ~N~N ~ ~ C = C - P _ y2Rl ICn Cl y3R2 40 - the compounds IDa.430 - IDa.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that R5 is the heterocycle ~2 where Rl~ ~ methyl, and Rll and Rl2 = trifluoro-- methyl:
0050/46586 CA 0224~6~9 1998-08-06 ~ . , .
_ H3C ~CH2- CH2--~--Y2Rl IDa Cl y3R2 10 - the compounds IDb.430 - IDb.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rl1 and R12 - trifluoromethyl:
--~ Cl ~yl , ~N - N'~ CH2 CH - ~ y2Rl IDb Cl y3R2 - the compounds IDc.430 - IDc.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~2 where R10 = methyl, and R1l and R12 ~ trifluoromethyl:
~ Br ~1 H C ~'N~CH2- CH - ~ y2Rl IDc f Cl y3R2 - the compounds IDd430 - IDd.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~2 where RlO = methyl, and Rl1 and Rl2 = trifluoromethyl:
CN yl ~N~N CH2--CH--! y2Rl IDd Cl y3R2 CA 022456~9 1998-08-06 c - the compounds IDe.430 - IDe.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~2 where R10 = methyl, and Rll and Rl2 = trifluoromethyl:
~=I~ CH3 yl ~N~N' ~ CH2 CH- P y2Rl IDe Cl y3R2 - the compounds IDf.430 - IDf.1287, which differ from the corres-lS po~ing compounds IAa.430 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~2 where Rl~ =
methyl, and Rll and R12 - trifluoromethyl:
CO ~-1 ~N'N' ~ CH2 CH - ~ y2Rl IDf Cl y3R2 - the compounds IDg.430 - IDg.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is 1,2-ethenediyl and RS is the heterocycle ~2 where Rl~ = methyl, and Rll and Rl2 = trifluoromethyl:
__ F3C CF3 ~ ~ yl H3C ~ 'N ~ t \ I IDg R4 ~ CH CH - ~ y Cl y3R2 40 - the compounds IDh.430 - IDh.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth i8 -CH=C(Cl)- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rll and R12 = trifluoromethyl:
_ _ , 77 ._ Cl yl -N ~ CH - C P YZRl IDh Cl y3R2 lO - the compounds IDi.430 - IDi.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle ~2 where Rl~ = methyl, and Rll and Rl2 s trifluoromethyl stehen:
~ Br yl (~' H3C N4 ~ CHC --~-- y2Rl IDi Cl y3R2 - the compounds IDj.430 - IDj.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle <p2 where R10 = methyl, and Rll and R12 = trifluoromethyl:
~ CN yl ,N~ N' ~ CH C --" _ y2Rl IDj Cl y3R2 - the compounds IDk.430 - IDk.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(CH3)-- and R5 is the neterocycie ~2 where R10 = rllethyl, ar.d Rll and R12 = trifluoromethyl.
CH3 yl N~N ~ ~:H C P y2Rl IDk \~/ I
C 1 ' y3R2 0050/465~6 - the compounds IDm.430 - IDm.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~2 where Rl0 = methyl, and R1l and R12 - trifluoromethyl:
F3C _~_____" CF3 lOH C ,N~ ~ CH C - ~ y2Rl IDm Cl y3R2 - the compounds IDn.~30 - IDn.1287, which differ from the corres-ponding compounds IAa.430 - IAa.1287 only in that Eth is -C_C-and R5 is the heterocycle ~2 where Rl~ - methyl, and Rll and R12 = trifluoromethyl:
C ~ C -- C - ' - Y2R1 IDn Cl y3R2 - the compounds IEa.l - IEa.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that R5 is the heterocycle ~3 where Y4 2 oxygen, and Rl3 and Rl4 together = a tetramethylene chain:
(~': 0~~
~ ~ CH2 CH2- 1 - Y2Rl IEa Cl y3R2 40 - the compounds IEb.l - IEb.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~3 where Y4 - oxygen, and R13 and Rl4 together = a tetramethylene chain:
1~ Cl yl IEb ~ ~--CH2--CH P--Y2R
Cl y3R2 10 - the compounds IEc.l - IEc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CR2-CH(Br)- and R5 is the heterocycle ~3 where Y4 5 oxygen, and R13 and Rl4 together = a tetramethylene chain:
C ~C~--C~--r_y2~1 IEc Cl y3R2 - the compounds IEd.1 - IEd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and R5 is the heterocycle ~3 where y4 2 oxygen, and Rl3 and R14 together - a tetramethylene chain:
N\ CN yl R4~ CH2 CH - 7 - y2Rl IEd t \=~
Cl y3R2 - the compounds IEe.1 - IEe.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 together = a tetramethylene chain:
~ O
~N\ CH3 yl IEe R4~ CH2--CH--~--Y2R
~
Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 -- the compounds I~f.l - I~f.1287, which differ from the corres-~ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(COOCH3)-- and R5 is the heterocycle ~>3 where Y4 5 oxygen, and R13 and R14 together = a tetramethylene chain:
C ~ ;D OCH3 IEf R4 ~ CH2- CH - P - Y2R
Cl y3R2 - the compounds IEg.1 - IEg.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~)3 where Y4 = oxygen, and R13 and R14 together -- a tetramethylene chain:
~0 N~ -~1 IEg R4 ~ CH CH - ? _ y2Rl Cl y3R2 - the compounds IEh.1 - IEh.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~)3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ C3 = C - I - YZR~ I~h C 1 y3R2 40 - the compounds IEi.1 - IEi.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle q'3 where Y4 = oxygen, and R13 and Rl4 together = a tetramethylene chain:
OOSO/46586 CA 02245659 l998-08-06 ~ ~ C~ = C - ~ - Y~R1 IEi Cl y3R2 lO - the compounds IEj.1 - IEj.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN) - and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
15 ~
.~ ~ N CN yl IE;
~ ~CH -- C ~ Y2R
Cl y3R2 - the compounds IEk.l - IEk.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 25 -CH=C (CH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ \ CH3 yl IEk r R4--~-- CH = C ' y2 Cl y3R2 - the compounds IEm.l - IEm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 together = a tetramethylene chain:
~ CO yl IEm R4 ~ CH = C ~ y2 Cl y3R2 OOSO/46586 CA 0224~6~9 1998-08-06 - the co...~ounds IEnl - IEn.1287, which differ from the corres-ponding c~ _~nds IAa.l - IAa.1287 only in that Eth is -C_C-and R5 iS the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 together 5 a tetramethylene chain:
~ O
N
Il \ yl IEn R4 ~ C C _ y2Rl Cl y3R2 - the compounds IFa.l - IFa.1287, which differ from the corres-ponding compounds IAa.l -- IAa.1287 only in that R5 is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 - methyl:
H3C ~ o ~ N
20 H3C 11 \ yl IFa R4 - ~ CH2 CH2- ~ y2 Cl y3R2 - the compounds IFb.l - IFb.1287, which differ from the corres-ponding col--~ounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(Cl)--and RS is the heterocycle ~3 where Y4 = oxygen, and R13 and R14 -- methyl:
H3C ~ O
~_ H3C ~ ~ ~ Cl yl IFb R4--~/ \ ~ CH2 CH ~ y Cl Y3RZ
- the compounds IFc.l - IFc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2--CH(Br)--and R5 iS the heterocycle ~P3 where Y4 = oxygen, and R13 and R14 = methyl:
~ . . . .
83 _ H3C ~ O
R4 ~ CH2 CH P _ y2R1 IFc Cl y3R2 10 - the compounds IFd.1 - IFd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2--CH(CN)--and Rs is the heterocycle q~3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ O
H3C \ CN yl IFd R4 ~ CH2 CH ~ y2 ~ y3R2 Cl - the compounds I~e.l - IFe.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(CH33-- and R5 is the heterocycle ~'3 where Y4 = oxygen, and R13 and Rl4 2 methyl:
H3C ~ O
H3C ~ ~ _ ~ CH3 yl IFe .~ R4 ~ CH2 CH ~ y2Rl Cl y3R2 - the compounds IFf.1 - IFf.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(COOCH3)-- and R5 is the heterocycle ~'3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ ~ OCH3 H3C ~ ~ CH2 CEi--P_ y2R1 IFf Cl y3R2 .
.
84 _ -- the compounds IFg.l -- IFg.1287, which differ from the corres--ponding compounds IAa.l -- IAa.1287 only in that Eth is 1,2--ethf-ne~liyl and R5 is the heterocycle ~P3 where Y4 = oxygen, and R13 and R14 = methyl:
5 H3C ~ O
H3C ~N\ yl IFg lOR4 ~ CH CH I Y2R
Cl y3R2 - the compounds IFh.l -- IFh.1287, which differ from the corres-15 pon-l;ng compounds IAa l -- IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~>3 where Y4 = oxygen, and R13 and Rl4 = methyl:
20H3C ~ffO
H3C ~~ \ Cl yl IFh 25R4~ CH -- C - P y C 1 y3R2 - the compounds IFi.l - IFi.1287, which differ from the corres--30 ponding cc,l..~ounds IAa l -- IAa.1287 only in that Eth is -CH=C(Br)-- and R5 is the heterocycle tp3 where Y4 -- oxygen, and ~ R13 and R14 = methyl:
H3C ~O
H3C ~N~ Br -1 IFi R4 ~ CH - C " y Cl y3R2 - the compounds IFj.l -- IFj.1287, which differ from the corres--ponding compounds IAa.l -- IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ~I~3 where Y4 = oxygen, and 45 R13 and R14 = methyl:
.
_ H3C ~ O
~ N
H3C --1~ \ CN yl IF;
R4 ~ CH C ~ - Y2R
Cl y3R2 lO - the compounds IFk.l - IFk.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 iS the heterocycle ~3 where Y4 = oxygen, and R13 and R14 = methyl:
H3C ~ O
.~ - H3C ~ N CH3 yl IFk R4 ~ CH l - ~ - y2Rl ~
Cl y3R2 - the compounds IFm.1 - IFm.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 iS the heterocycle ~tp3 where Y4 = oxygen, and Rl3 and Rl4 3 methyl:
H3C ~ O OCH3 ~ N
H3C ~ CO yl IFm .. _ R4 ~ CH C - P y2 Cl y3R2 - the co.--~ounds IFn.1 - IFn.1287, which differ from the corres-ponding compounds IAa.l -- IAa~ 1287 only in that Eth is --C_C--and R5 is the heterocycle ~3 where Y4 = oxygen, and Rl3 and Rl4 e methyl:
H3C l~ ~ -11 IFn 45R4 ~ C _ C y2 C1 y3R2 0050/46586 CA 0224~6~9 l998-08-06 - the compounds IGa.1 - IGa.1287, which differ from the corres-ponding col--~ounds IAa.1 - IAa.1287 only in that R5 is the heterocycle ~4 where Rl5 and R16 together z tetramethylene chain and Rl7 = chlorine:
~ N
Cl \A yl IGa R4 ~ / \ ~ CH2 CH2- ~ - Y2R
~
Cl y3R2 - the compounds IGb.1 - IGb.1287, which differ from the corres-15 ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CR(Cl)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~ Cl \ Cl yl R4 ~ CH2 CH - ~- y2Rl IGb C 1 y3R2 - the compounds IGc.1 - IGc.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
__ ~ N
~N~ Br yl Cl ~ CH2 CH _ y2Rl IGc Cl y3R2 40 - the compounds IGd.l - IGd.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and RS is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
0050/46586CA 0224~6~9 l998-08-06 -~'~'~___N
N
~ CN yl R4 ~ -CH2 CH - P y2Rl IGd Cl y3R2 lO - the compounds IGe.1 - IGe.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
~'--~7___N
~ N
R4 ~ CH2 - C~ - ~ - y2Rl IGe Cl y3R2 - the compounds IGf.1 - IGf.1287, which differ from the corres-pbnding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
~ N l~cCo~3 yl Cl ~ CH2 - CH - I - Y2Rl IGf Cl y3R2 - the co...~ounds IGg.1 - IGg.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethene~;yl and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chsin and Rl7 = chlorine:
~ N
~ CH = C~ - ~ - Y~RI IGg Cl y3R2 0050/46586 CA 0224~6~9 1998-08-06 - the compounds IGh.l - IGh.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~~~ __N
~ Cl yl R4 ~ CH C - y2Rl IGh Cl y3R2 - the compounds IGi.l - IGi.1287, which differ from the corres-ponding co,..~ounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and R17 ~ chlorine:
~ N
~ N Br yl R4 ~ CH = C - P - YZRI IGi Cl y3R2 - the compounds IGj.l - IGj.1287, which differ from the corres-ponding co---~ounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~4 where Rl5 and R16 together = tetramethylene chain and Rl7 = chlorine:
N
N
Cl \r-~ CN ~~1 IGj R4 ~ CH = C - ~ - y Cl y3R2 40 - the compounds IGk.l - IGk.1287, which differ from the corres-ponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~i where Rl5 and R16 together = tetramethylene chain and R17 = chlorine:
~~~____N
~ ~, Cl ~I _ I _ y2Rl }Gk Cl y3R2 lO - the compounds IGm1 - IGm.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~4 where Rl5 and Rl6 together = tetramethylene chain and Rl7 = chlorine:
~~~ __N OCH3 ~ N CO yl CH - C YZRl IGm Cl y3R2 - the compounds IGn.1 - IGn.1287, which differ from the corres-ponding compounds IAa.1 - IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~4 where R15 and R16 together =
tetramethylene chain and Rl7 - chlorine:
N
N yl C C ~ y2Rl IGn Cl y3R2 - the compounds IHa.1 - IHa.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
0050/46~86 F2HC\ Cl N ~ /
H3C ~ \ l ~-1 IHa R4~ CH2 CH2 ? y2 Cl y3R2 - the compounds IHb.l - IHb.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~5 where Rl3 = chlorine, Rl9 - difluoromethyl and R20 8 methyl:
F2HC Cl H3C ~ \ ~ Cl -.1 \ I IHb R4~ CH2--CH ~ y2 Cl y3R2 - the compounds IHc.l - IHc.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~5 where R18 = chlorine, Rl9 s difluoromethyl and R20 - methyl:
~~ - F2HC\ Cl ~1 /
H3C ~ \ ¦ \ Br ~-1 R4 - ~ CH2 - CH ~ y2Rl IHc Cl y3R2 - the compounds IHd.l - IHd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(CN)- and Rs is the he~erocycle ~5 where Rl3 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC\ Cl H3C~
N ~ CN ~1 IHd R4 ~ CH2 - CH ~ y Cl y3R2 - the compounds IHe.1 - IHe.1287, which differ from the corresponding ~ r~ounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
\ ~/
20 H3C ~ \ ~ CH3 ~rl IHe R4 ~ CH2 - CH - ' - Y2R
Cl y3R2 - the co..~ounds IHf.l - IHf.1287, which differ from the corresponding col..~o~nds IAa1 - IAa.1287 only in that Eth is -CH2-CH(COOCH3)- and R5 is the heterocycle ~5 where R18 =
chlorine, Rl9 = difluoromethyl and R20 = methyl:
--- F2HC Cl N ~ OCH3 H3C~,\ ~ CO ~rl IHf R4 ~ CH2 CH - ' YZR
Cl y3R2 - the compounds IHg.l - IHg.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~5 where Rl8 =
chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC Cl H3C ~ \ ~ yl ~ I IHg R4 ~ / \ ~ CH CH - ~ - y2R1 C 1 y3R2 - the compounds IHh.1 - IHh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~5 where R18 = chlorine, 15 R19 3 difluoromethyl and R20 = methyl:
F2HC Cl \ /
20 H3C ~ \ 3 Cl yl R4 ~ CH C- ~ - y2Rl IHh C 1 y3R2 - the compounds IHi.1 - IHi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth i~
-CH=C(Br)- and R5 is the heterocycle ~5 where R13 3 chlorine, R19 = difluoromethyl and R20 = methyl:
F2HC Cl H3C ~ \ ~ Br -rl IHi R4 ~ / \ ~ CH - C - ~ - y2Rl C 1 y3R2 - the compounds IHj.1 - IHj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 - difluoromethyl and R20 = methyl:
0050/46586 CA 0224~6~9 1998-08-06 ~. .
-N
H3C~
N- CN yl R4 _ ~ CH = C - ~ y2Rl IHj Cl y3R2 - the compounds IHkl - IHk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~5 where Rl8 = chlorine, Rl9 = difluoromethyl and R20 = methyl:
F2HC\ Cl H3C ~ \ ¦ CH3 ~1 IHk R4 _ ~ CH - C - ~ y2 Cl y3R2 - the compounds IHm.l - IHm.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~5 where R18 =
chlorine, Rl9 - difluoromethyl and R20 = methyl:
F2HC Cl \ / OCH3 N-3C ~ \ ¦ CO -~1 I IHm R4 ~ CH = C - ~ - y Cl y8R2 - the compounds IHn.l - IHn.1287, which differ from the corresponding compounds IAal - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~5 where Rl8 c chlorine, Rl9 -difluoromethyl and R20 = methyl:
F2HC\ Cl N ~
H3C~\ I ~l I~n R4 ~ C C ~ - Y2R
Cly3R2 - the compounds IKa.1 - IXa.1287, which differ from the corresponding compounds IAa.1 -- IAa.1287 only in that R5 is the heterocycle ~7 where Y7 3 oxygen, and R23 and R24 together =
tetramethylene chain:
N'~N
yl IKa R4 ~ CH2 CH2- ~ - Y2R
C 1 y3R2 - the compounds IRb.1 - IKb.1287, which differ from the correspon~;ng compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(Cl)--and R5 is the heterocycle ~>7 where Y7 ~ oxygen, and R23 and R24 together = tetramethylene chain:
N'~N
O ~ Cl ~1 IRb R4 ~ CH2 CH - ~ y2 Cl y3R2 - the compounds IKc.1 - IKc.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(Br)--and R5 is the heterocycle ~7 where Y7 = oxygen, and 4S R23 and R24 together = tetramethylene chain:
, ._ ~ N Br ~rl O I IKc R4 ~ CH2 - CH y Cl y3R2 - the compounds IXd.l - IXd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2-CH(CN)-- and R5 is the heterocycle ~7 where Y7 ~ oxygen, and R23 and R24 together - tetramethylene chain:
~N ~ N
O CN --1 IKd R4 ~ CH2 - CH- ? y2 C 1 y3R2 - the compounds IRe.1 - IRe.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(CH3)-- and R5 is the heterocycle ~>7 where y7 2 oxygen, and R23 and R24 together c tetramethylene chain:
~N ~ N
~ N CH3 --1 O \ I IXe R4 ~ CH2 - CH ? - Y2R
Cl y3R2 - the compounds IKf.1 - IKf.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CHz--CH(COOCH3)-- and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
, 96 ._ N'--~N
~ N CO yl R4 ~ CH2 CH n y2Rl IRf Cl y3R2 - the compounds IKg.1 - IKg.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethene~l;yl and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together - tetramethylene chain:
N "~N
o~N ~~l IKg R4 ~ ~ CH CH . y2 Cl y3R2 - the compounds IKh.l - IKh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)-- and R5 is the heterocycle ~P7 where Y7 = oxygen, and R23 and R24 together -- tetramethylene chain:
N N
o ~ N Cl yl R4 ~ CH ~ C P y2Rl IRh Cl y3R2 - the compounds IKi.1 - IKi.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH=C(Br)--and R5 is the heterocycle q~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
~ . .
~ N
o ~ N ~ Br yl IKi R4 ~ CR C - ~ y2 Cl y3R2 - the compounds IKj.l - IRj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)-- and R5 is the heterocycle ''P7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
N N
0N CN yl IKj R4 ~ CH - C ~ y Cl y3R2 - the compounds IKk.l - IKk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CR=C(CH3)-- and R5 is the heterocycle ~7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
1 ~ N
, ~ N CH3 yl R4 ~ CH C "--y2Rl IKk Cl y3R2 - the compounds IKm.1 - IKm.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(COOCH3)-- and Rs is the heterocycle 'P7 where Y7 = oxygen, and R23 and R24 together = tetramethylene chain:
98 . _ N N
~N CO ~rl \ I IKm R4 ~ CH -- C--~~ y2 Cl y3R2 - the compounds IKn.l - IRn.1287, which differ from the correspo~;ng compounds IAa.l - IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~7 where Y7 z oxygen, and R23 15 and R24 together = tetramethylene chain:
~.
N N
1 IKn R ~ ~ C C - ~ - Y2Rl ~ .
Cl y3R2 - the compounds ILa.l - ILa.1287, which differ from the corresponding c~--l~ounds IAa.1 - IAa.1287 only in that R5 is the heterocycle ~20 where R50 - methyl, R5l = trifluoromethyl and R52 = hydrogen:
(~' ~
S ~ N - CH3 3S N -rl ~ - ILa R4 ~ CH2 - CH2 - y Cl y3R2 - the compounds ILb.1 - ILb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~20 where R50 = methyl, R5l ~ trifluoromethyl and R52 ~ hydrogen:
0050/46586 CA 0224~6~9 l998-08-06 ~ 99 ~ CF3 S~N CH3 R4~CH2 C~--I'_ y2Rl ILb Cl y3R2 - the compounds ILc.l -- ILc.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CH2--CH(Br)--and R5 is the heterocycle ~20 where R50 = methyl, 15 R5l -- trifluoromethyl and R52 = hydrogen:
~, ~ .
S~N-- CH3 N Br ~,l R4 ~ CH2--CH2--~--Y2Rl ILc Cl y3R2 - the compounds ILd.l -- ILd.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle ~p20 where R50 - methyl, 30 R51 -- trifluoromethyl and R52 8 hydrogen:
~' ~f S~N CH3 N CN ~1 ILd R4 ~ CH2 CH2--? _ y2Rl C 1 y3R2 - the compounds ILe.1 -- ILe.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is - --CH2--CH(CH3)-- and R5 is the heterocycle ~I~20 where R50 = methyl, 45 R5l = trifluoromethyl and R52 = hydrogen:
100 ' -S ~ N CH3 N CH3 yl R4 ~ CH2 CH- ~ y2Rl ILe Cl y3R2 - the compounds ILf.1 - ILf.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH~COOCH3)- and R5 is the heterocycle ~20 where R50 =
methyl, R5l = trifluoromethyl and R52 = hydrogen:
~' ~
S ~ N CH3 OCH3 N CO yl R4 ~ CH2 - CH ~ y2Rl ILf Cl Y3R2 - the c~...~ounds ILg.l - ILg.1287, which differ from the correspo~;ng compounds IAa.1 - IAa.1287 only in that Eth is 1,2--e~hene~l;yl and R5 i6 the heterocycle ~20 where R50 = methyl, R5l = trifluoromethyl and R52 = hydrogen:
~' ~
S ~ N CH3 N yl R4 ~ CH CH P Y2Rl ILg Cl y3R2 - the compounds ILh.1 - ILh.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~20 where R50 - methyl, R5l = trifluoromethyl and R52 = hydrogen:
.
, 0050/46586 CA 0224~6~9 1998-08-06 S~,N CH3 N ~ Cl yl ILh R4 ~ / \ ~ CH - C ~ y Cl y3R2 - the compounds ILi.l - ILi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~20 where R50 = methyl, R51 = trifluoromethyl and R52 = hydrogen:
f ~
S ~ N CH3 N Br ~1 ~ I ILi R4 ~/ \ ~ CR - C - ~ y Cl y3R2 - the compounds ILj.l - ILj.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~20 where R50 = methyl, R51 - trifluoromethyl and R52 = hydrogen:
._ ~
S ~ N CH3 N CN ~-1 ~ I ILj R4 ~ CH - C -Cl y3R2 - the compounds ILk.l - ILk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~20 where R50 = methyl, R5l = trifluoromethyl and R52 = hydrogen:
~ .
S~N-- CH3 ~ I ILk R4--(/ \~ CH C ? y2 Cl y3R2 - the compounds ILm.l -- ILm.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is --CHsC(COOCH3)-- and R5 is the heterocycle ~20 where R50 = methyl, 15 R51 = trifluoromethyl and R52 - hydrogen:
_ CF3 ~, ~
S~N-- CH3 oCH3 N CO yl R4~ CH CH--~--y2Rl ILm Cl y3R2 - the compounds ILn.l -- ILn.1287, which differ from the corresponding compounds IAa.l -- IAa.1287 only in that Eth is -C_C- and R5 is the heterocycle ~20 where R50 s methyl, R51 =
30 trifluoromethyl and R52 ~ hydrogen:
1~ ~ .
S~N CH3 ILn R4 ~ C C - ~--Y2R
Cl y3R2 - the compounds IMa.l -- IMa.1287, which differ from the corresponding compounds IAa.l -- IA.1287 only in that R5 is the heterocycle ~21 where Z3 and Z4 = nitrogen, and R53 and R54 45 together = tetramethylene chain:
CA 0224~6~9 1998-08-06 .
N ~/
N ~ S
~ 5 N ~rl \ - IMa R4 ~ CH2 CH2- ' - Y2R
Cl y3R2 - the compounds IMb.l - IMb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
~, /~ O
.~ ~ ~N ~/
N~ ~ S
N Cl -~1 \ I IMb R4 ~ CH2 CH - ~ y2 Cl y3R2 - the compounds I~c.1 - IMc.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2-CH(Br)-- and R5 is the heterocycle q~21 where Z3 and Z4 =
nitrogen, and Rs3 and R54 together = tetramethylene chain:
/~ o ~N ~//
N ~ S
N Br .1 \ I IMc R4 ~ CH2 CH Y2R
Cl y3R2 - the compounds IMd.l - IMd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle q~21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
oo~o/46~86 CA 02245659 1998-08-06 .
.
~ ~ .
N y S
N CN yl R4 ~ CHz CH--P _ y2R1 IMd Cl y3R2 - the compounds IMe.1 - IMe.1287, which differ from the correspon~ing compounds IAa.l - IAa.1287 only in that Eth is --CHz--CH(CH3)-- and R5 is the heterocycle ~I>21 where Z3 and Z4 z nitrogen, and R53 and R54 together = tetramethylene chain:
. . /~ O
~N ~//
N ~ S
N CH3 yl \ I i IMe R4 ~ CH2 CH y Cl y3R2 - the compounds IMf.l - IMf.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(COOCH3)- and R5 iS the heterocycle ~Zl where Z3 and Z4 =
30 nitrogen, and R53 and R54 together -- tetramethylene chain:
/~ . O
f - ~, N ~/
N ~ S OCH3 11 l N CO yl I IMf R4 ~ CH2 CH - ~ y Cl Y3RZ
- the compounds IMg.l - IMg.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is 1,2--ethenediyland R5 is the heterocycle ~21 where Z3 and Z4 nitrogen, and R53 and R54 together = tetramethylene chain:
0050/46586 CA 0224~6~9 1998-08-06 105 ~
N ~//
N ~ S
Il N ~-1 \ IMg R4 ~ ~ CH CH- ? _ y2Rl Cl y3R2 - the compounds IMh.l - IMh.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(Cl)--and R5 is the heterocycle <~>21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
/~ O
~_ ~ /N ~
N ~ S
N\ Cl ~-1 R4 ~ ~ CE~ C--~ y2Rl IMh C 1 y3R2 - the compounds IMi.l - IMi.1287, which differ from the corresponding ~.~o~nds IAa.l - IAa.1287 only in that Eth is --CH-C(Br)-and R5 is the heterocycle ~p21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
N ~/
-- N ~ S
N Br yl R4 ~ CH C--~--y2Rl IMi Cl y3R2 - the compounds IMj.l - IMj.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(CN)-and R5 is the heterocycle tp21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
~ 0050/46586 CA 02245659 1998-08-06 .
'' 106 --/~ O
/ ~
N ~ S
N CN yl IMj R4 ~ CH - C ' y2 Cl y3R2 - the compounds IMk.l - IMk.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is --CH=C(CH3)-- and R5 is the heterocycle ~>21 where Z3 and Z4 =
nitrogen, and R53 and R54 together = tetramethylene chain:
/~ O
~N ~/~
N ~ S
N CH3 ~1 ~ I IMk R4 ~ CH C - ? _ y2 Cl y3R2 - the co",~ounds I~l - IM~1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle q~21 where Z3 and Z4 30 nitrogen, and R53 and R54 together = tetramethylene chain:
N ~
~ I
I IMm R4--~ ~ CH C - ? y2 Cl y3R2 - the compounds IMn.l - IMn.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -C_C- and R5 iS the heterocycle ~>21 where Z3 and Z4 = nitrogen, and R53 and R54 together = tetramethylene chain:
CA 02245659 l998-08-06 N //~
N ~ S
N -rl \ IMn R4 ~ C -- C --n y2Rl Cl y3R2 - the cGl..~ounds INa.1 - INa.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that R5 iS the heterocycle ~22 where R55 and R56 together = 2,2-dimethyl-propane-1,3-diyl chain:
H3C ~ N ~ S
N ~rl ~ INa R4 ~ ~ CH2--CH2-- '_ Y2R
Cl y3R2 - the compounds INb.1 - INb.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(Cl)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
C H3C ~ N ~ ~N
N Cl yl R4 ~ C~2 CH - ~ y2Rl INb Cl y3R2 - the compounds INc.1 - INc.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH2-CH(Br)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
~ 0050/46586 CA 02245659 1998-08-06 ~ , 108 ~~
H3C ~ N ~ S
N Br --1 R4 ~ CH2 CH ; y2Rl INc Cl y3R2 - the ~ o~nds INd.l - INd.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is --CH2--CH(CN)--and R5 is the heterocycle ,~p22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ r==~N
N CN ~-1 R4 ~ CH2 CH - ~ y2Rl INd Cl y3R2 - the compounds INe.l - INe.1287, which differ from the corresponding co~l~ounds IAa.l - IAa.1287 only in that Eth is -CH2-CH(CH3)- and R5 is the heterocycle <~22 where R55 and R56 together - 2,2-dimethylpropane-1,3-diyl chain:
_ H3C ~ N ~ S
~ CH3 ~~1 R4 ~ CH2 CH y2Rl INe Cl y3R2 - the compounds INf.l - INf.1287, which differ from the corresponding col-l~ounds IAa.l - IAa.1287 only in that Eth is --CH2--CH(COOCH3)-- and R5 is the heterocycle ~p22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
.
H3C ~ ~N fCH3 \ I INf R4 ~ CH2 - CH2- ~ y Cl y3R2 - the compounds INg.1 - INg.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is 1,2-ethenediyl and R5 is the heterocycle ~22 where Rs5 and R56 together z 2,2-dimethylpropane-1,3-diyl chain:
~0~ -~1 INg R4 ~ CH - CH ~ y2 25Cl y3R2 - the col-,~ounds INh.1 - INh.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Cl)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
~- H3C ~ N ~ ~N
35N Cl yl \ I I INh R4 ~ CH C - ~ y2 Cl y3R2 - the compounds INi.l - INi.1287, which differ from the corresponding compounds IAa.l - IAa.1287 only in that Eth is -CH=C(Br)- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
0050/46586 CA 02245659 l998-08-06 110 ' - ' 3C ~ N ~r R4 ~ CH - C _ y2R1 Cl y3R2 - the compound5 INj.1 - INj.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CN)- and R5 is the heterocycle ~22 where R55 and Rs6 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ r--_N
H3C I N ~ S
N Br vl R4 ~ CH - C - ~ _ y2Rl INj Cl y3R2 - the compounds INk.l - INk.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(CH3)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ N
H3C I N ~ S
N\ CH3 i~l INk R4 ~ CH C ~ - y2 Cl y3R2 - the compounds INm.1 - INm.1287, which differ from the corresponding compounds IAa.1 - IAa.1287 only in that Eth is -CH=C(COOCH3)- and R5 is the heterocycle ~22 where Rs5 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
E33C ~ N ~ 5 oc~3 N CO '1 INm R4 ~ CH- C - ~ y2Rl C 1 y3R2 - the compounds INn.1 - INn.1287, which differ from the corresponding co...~ounds IAa.1 - IAa.1287 only in that Eth is -C-C- and R5 is the heterocycle ~22 where R55 and R56 together = 2,2-dimethylpropane-1,3-diyl chain:
H3C ~ N
~3C N S
~
N yl R4 ~ CC ' y2Rl INn Cl y3R2 The substituted aromatic phosphonic acid derivatives of the for-30 mula I are ob~;n~hle by a variety of routes, in particular byone of the following processes:
~- A) linkage of the phosphonyl group to the aromatic ring 35 A.l) by dia~otizing anilines II and reacting the resulting dia-zonium salts with vinyl- or alkynylphosphonic acid deriva-tives III by the Meerwein method {cf, for example, Org.
Reactions 11 (1960), chapter 3, pp. 189-260 and Kogyo Kagaku Zasshi 67(12) (1964), 2093-2095}:
-CA 0224~6~9 1998-08-06 Cl/Br diazotization ArNH2 yl ~ Ar--CH2 CH P--y + ~2C = CH - ~ Y2R1 ~salt ) y3R2 ~ Eth=CH2CHCl, CH2CHBr~
IIIa y3R2 Cl/Br yl --r I
ArNH2 diazotization 3 Ar - CH = C P - y2R1 + HC 3C LY2R1 G~) Y3R2 ¦ ~a J I~Eth=CH = CCl, CH - CBr 15IIIb y3R2 ~
_. / \
Ar ~ R4 ~
\ R3 /
In this method, the aniline of the formula II, which i8 either known from the literature or can be synthesized s;m;l~rly to An;l;nes known from the literature, is first converted into the corresponding diazonium cation in a ~-nner known per se, and this is then reacted completely with IIIa or IIIb in the presence of a copper salt.
The diazonium salt is generally obt~;n~ by reacting the C ~n; 1; ne II with a nitrite, such as sodium nitrite and potassium nitrite, in an aqueous acid solution, e.g. in aqueous hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid or tetrafluoroboric acid. The nitrite is normally employed in approximately equimolar amounts or in an excess of up to approximately five times the molar amount based on the amount of ~n; ~; ne II.
The resulting solution of the diazonium salt, or the diazo-nium salt isolated therefrom, is then reacted with a sol-ution or suspension of the vinyl- or alkynylphosphonic acid derivative IIIa/IIIb in the presence of a copper salt, such as copper(I) bromide~ copper(II) bromide copper( I ) chlor-ide and copper(II) chloride.
- 0050/46586 CA 0224~6~9 1998-08-06 .
Examples of suitable solvents are water, acetonitrile, ke-tones such as acetone, diethyl ketone and methyl ethyl ke-tone, ethers such as diethyl ether and tetrahydrofuran, and furth~-~ore alcohols such as methanol or ethanol.
The vinyl- or alkynylphosphonic acid derivatives IIIa/IIIb and the copper hA 1; ~e are normally used in approximately equimolar amounts or in an excess of up to approximately 30 times the molar amount based on the ~n;l;ne II. However, it is possible to employ a lesser or catalytic amount of the copper halide.
As a rule, the diazotization and the reaction of the diazo-nium salt with IIIa/IIIb are carried out at from (-100) to 50~C, preferably (-20) to +30~C.
One process variant consists in an addition to a solution or suspension of the aniline II, of the vinyl or alkynyl-phosphonic acid derivative IIIa/IIIb and of the copper halide in an anhydrous system, e.g. in glAc;~l acetic acid~
chlorohydrocarbon, absolute methanol or ethanol, in an ether such as tetrahydrofuran and dioxane or in aceto-nitrile or acetone, a nitrous ester such as tert-butyl ni-trite and isopentyl nitrite. What has been said above re-garding the reaction temperature and the ratios of the re-actants also applies here.
A.2) by means of a Heck reaction (see, for example, B. A. Buri-ni, S. Cacchi, P. Pace, B.R. Pietroni, Synlett 1995, 677):
Ra yl Ra yl ~5 Ar - ~Br +H2~=l , _ y2Rl bcaaSte~ Ar- CH = C P y2Rl y3R2 y3R2 IV V I~Ra = H, CN, halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, ( Cl-C4-alkoxy )--carbonyl, di(Cl-C4-alkyl)-amino - 0050/46586 CA 0224~6~9 1998-08-06 ~s ,, As regards the definition of Ar, see Process A.1);
cat. is a transition-metal catalyst, preferably a palla-dium(II) compound such as palladium acetate.
As a rule, the reaction is carried out in an inert organic solvent, in particular in dimethylformamide or tetrahy-drofuran.
~xamples of suitable bases are carbonates such as potassium carbonate, acetates such as sodium acetate and tertiary amines such as triethyl A~; ne .
The reaction is generally carried out at from 0~C to the boiling point of the reaction mixture, preferably at 50 to 100~C.
~.
A.3) by means of Rnoevenagel condensation of aromatic aldehydes VIa or ketones VIb with phosphonic acid derivatives VII:
Ar- CHO (VIa) ~ + Rb_CH2 ,l_y2Rl~cat.
Ar- CO-(Cl-C4-alkyl) VIb ~ y3R2 VII H/Cl-C4-alkyl Ar c=f--P y2Rl Rb y3R2 ~~- As regards the definition of Ar, see process A.1);
b iS cyano, Cl-C4-alkoxy or (Cl-C4-alkoxy)carbonyl (VIIa ~ VII where Rb - CN; VIIb = VII where Rb = alkoxy);
cat. is a catalyst, e.g. piperidine/acetic acid, sodium methanolate, sodium ethanolate, titanium tetrachlo-ride/N-methylmorpholine, or chlorotri(isopropoxy)ti-tanium/triethyl A~i n~ .
The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a lower alcohol such as methanol and ethanol, or in a chlor-inated hydrocarbon such as dichloromethane.
- , 0050/46586 CA 0224~6~9 l998-08-06 115 _ The reaction temperature is generally at from 0~C to the boiling point of the reaction mixture.
If desired, the water which is freed during the reaction can be LeLI~ved by means of azeotropic distillation. In this case, the process is preferably carried out in an aromatic hydrocarbon such as ben7ene, toluene and the xylenes at the respective boiling point of the reaction mixture. {See, for example, S. Ab'lAllAh-El Ayoubi, F. Texier-Boullet, J. Hame-lin, Synthesis 1994, 258; D. Danion, R. Carrie, Tetrahedron Lett. 1968, 453?; F. Texier-Boullet, A. Foucaud, Tetrahe-dron Lett. 21 (1980), 2161; S. Patai, A. Schwartz, J. Org.
Chem. 25 (1960), 1232; J.M. McIntosh, R.A. Sieler, Can. J.
Chem. 56 (1978), 226; M.T. Reetz, R. Peter, M. v. Itzstein, - Chem. Ber. 120 (1987) 121; R.A. Petrov, V.A. Chauzov, S.V.
Agafonov, N.V. Pazhitnova, J. Gen. Chem. USSR 50 (1980), 1225}.
Those aromatic aldehydes VIa or ketones VIb which are not already known can be prepared in a manner known per se.
A.4) by means of Wittig-Horner olefination {cf., for example, B.M.G.T. Lowen, M.R. Almond, J. Org. Chem 59 (1994) 4548;
P. Teulade, P. Savignac, E.E. Aboujaoude, S. Lietge, N.
Collignon, J. Org~nt -L. Chem. 304 (1986), 283; G.M. Par-ratt, J. Chem. Soc., Perkin Trans. 1 (1986), 1417; B.
Costisella, I. Reitel H. Gross, Tetrahedron 37 (1981), 1227}:
Ar CHO (VIa) C- - ~- y VIb R~ y3R2 /
VIII
H/Cl--C~l yl I Ar - C = C y RC y3R2 - As regards the definition of Ar, see process A.1);
RC is hydrogen, halogen, Cl-C4-alkyl or di(Cl-C4-alkyl)amino (VIIIa = VIII where Rc = H;
VIIIb = VIII where Rc = halogen; VIIIc = VIII where Rc = alkyl).
-, 0050/46586 CA 0224~6~9 l998-08-06 The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a halogenated hydrocarbon such as dichloromethane or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
The anion VIII can be obtained, for example, by deprotonat-ing the corresponding methanediphosphonic acid derivative with a strong base such as lithium diisopropyl ~m j ~ ~ sodium hydride and n-butyllithium.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at lS from (-78) to +30~C.
- A.S) by means of Wittig olefination {see, in this context, for example GB-A 12 43 214~:
Ar - CH0 (VIa) ' + Ph3P = CH - y Ar - C0 - (C1-C4-alkyl) VIb J -~3R2 H/Cl-C4-alkyl V
~-Ar C = CH y I y3R2 As regards the definition of Ar, see process A.l);
Ph is the phenyl group.
The process is normally carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene, a halogenated hydrocarbon such as dichloromethane or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from 20 to 60~C. -- ~ OO~O/46586 CA 02245659 1998-08-06 A.6) by means of Peterson olefination {see, in this context, for example O.I. Kolodyazhnyi, D.B. Golokhov, J. Gen. Chem.
USSR 57 (1987), 2353; F.A. Carey, A.S. Court, J. Org. Chem.
37 (1972), 939}:
Ar-CHO (VIa) H ~ -alkyl Ar_CO _ alkyl*) (VIb) ¦
10 Ar_ CO - haloalkyl~) (VIc) ~CR2 ~--Y2R
Ar- CO - dialkyl~)amino (VId) X y3R2 strong base, ~ (C~3)3SiCl ._~
R/Cl-C4-alkyl I y Ar - C = C - P y y3R2 ~)each Cl-C4 Htalkyl~) haloalkyl~) I
dialkyl*)amino The process is norr-lly carried out in an inert organic solvent, e.g. in an aromatic hydrocarbon such as toluene or an ether such as diethyl ether, tetrahydrofuran, dioxane and 1,2-dimethoxyethane.
Examples of suitable strong bases are lithium diisopropyla-mide, sodium hydride or butyllithium.
In general, the reaction is carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from (-70) to +30~C.
Preferably, X is ~irst reacted with chlorotrimethylsilane in the presence of a strong base, and only then is the reaction product treated with a compound VIa to VId. As a 4S rule, the base is used in an excess, approximately 2 to 5 times, in particular approximately 2 times, the molar amount based on the amount of X. Chlorotrimethylsilane is . ~ 0050/46586 CA 0224~6~9 l998-08-06 :
expediently employed in an approximately equimolar amount based on the amount of X.
Those aromatic aldehydes VIa, ketones VIb and VIc and the N,N-dialkylbenz~m;~es VId which are not already known can be prepared in a m~nner known per se.
A.7) by means of subjecting a styryl h~l ;Ae XI to a coupling reaction with a trialkyl phosphite XII or a dialkyl phos-phite XIII {cf. in this context, for example, R.S. Gross, S. Mehdi, J.R. McCarthy, Tetrahedron Lett. 34 (1993), 7197;
G. Axelrad, S. Laosooksathit, R. Engel, J. Org. Chem. 46 (1981), 5200}:
-- PtO(C1-C4-alkyl)]3 Br XII
Ar C = C - I
1 1 ~ or Rd Re Hpoto(cl-c4-alkyl)]2 XI
,XIII ~ \
~1 o Ar C = C - P O(C1-C4-alkyl) ld le O( Cl--C4--alkyl ) I (y1~y2~y3 = o) c As regards the definition of Ar, see process A.1);
Rd and Re are hydrogen, halogen or Cl-C4-alkyl.
The process is nor~-lly carried out in an inert organic solvent, preferably in an aromatic hydrocarbon such as toluene or an ether such as tetrahydrofuran.
The reaction of XI with a trialkyl phosphite XII is advan-tageously carried out in the presence of copper(I) b or copper(I) chloride.
~ 0050/46586 CA 0224~6~9 l998-08-06 The reaction of XI with a dialkyl phosphite XIII is advan-tageously carried out in the presence of a transition-metal catalyst, preferably a palladium(II) compound, such as dichlorobis(triphenylphosphine)palladium, and, if desired, in the presence of a base, e.g. triethylamine.
The reaction is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at approximately +25~C.
Those styryl h~ es XI and phosphorus compounds XII and XIII which are not already known can be prepared in a ~-nner known per se.
A.8) by reacting a phenylacetylene XIV
- with a trialkyl phosphite XII or - in succession with phosphorus pentachloride and an alcohol, mercaptan or amine (HY2Rl/HY3R2) in the pres-ence of a base ~cf. in this context, for example, C.E. Griffin, T.D.
Mitchell, J. Org. Chem. 30 (1965), 1935; A. Meisters, J.M.
Swan, Aust. J. Chem. 18 (1965), 155; L. Maier, Synth.
Inorg. Met. Org. Chem. 3 (1973), 329; A.A. Petrov, J. Gen.
Chem. USSR 41 (1971) 1670}:
~ or XII or Ar - C-C - ~cl-c4-alkyl 1) PCl5 2) RY
XIV or HY3R2 ~ H/Cl P(O~ -O(Cl-C4-alkyl)l ~ ' - J 2' 35Ar - C = C P(O)(Y2Rl)(y3R2) I ~ ~ I Eth= ethenediyl, I chloroethene-H/C1-C4-alkyl diyl As regards the definition of Ar, see process A.1).
XIV is preferably reacted with XII in the absence of a sol-vent at from 20~C to the boiling point of the trialkyl phosphite XII, in particular at the boiling point of the reaction mixture.
. ~ 0050/46586 CA 0224~6~9 l998-08-06 Suitable bases for reacting the phenylacetylene XIV with PCl5 and (HY2Rl/HY3R2) are, in particular, tertiary ~mine~
such as pyridine and triethyl~mi ne.
XIV is preferably reacted with PCls at from 50 to 200~C, in contrast to the subsequent reaction with (HY2Rl/HY3R2), where the reaction temp~rature is from (-100)~C to the boiling point of the reaction mixture.
Those phenylacetylenes XIV and the alcohols, mercaptans and ~ineS (HY2Rl/HY3R2) which are not already known can be pre-pared in a ~Anner known per se.
15 A.9) by reacting benzyli~enetriphenylphosphoranes XV with a per-fluoroAlk~necarboxylic anhydride and subsequently with a lithium dialkyl phosphite in a ~onner known per se {cf. in ~- this context, for example, Y. Shen, Q. Liao, W. Qiu, J.
Chem. Soc., Perkin Trans l, 695 (l990)}:
20 P(Ph)3 (F3C-C02)0~ lithium dialkyl-)~ H or (F3C-CF2-C0)20 phosphit \
Ar ~Cl-C4-alkyl XV H/Cl-C4-alkyl 0 Ar C = IC P O(Cl-C4-alkyl) o ( cl-c4-alkyl, I ~yl~y2~y3 = o~ CF3/C2F5 As regards the definition of Ar, see process A.1);
Ph is the phenyl group.
Suitable solvents~diluents for XV are, in particular, aro-matic hydrocarbons, such as toluene and ethers such as tetrahydrofuran.
The reaction can generally be carried out at ~rom ~-100)~C
to the boiling point of the reaction mixture, preferably at from (-78) to +25~C.
Those benzylidenetriphenylphosphoranes XV which are not already known can be prepared in a ~onne~ known per se.
. ~ 0050/46586 CA 0224~6~9 1998-08-06 A.10) by alkylating a phosphonic acid derivative XVI with a 3-pyridylbenzyl h~ e XVII in a mAnn~r known per se in the presence of a strong base {cf. in this context, for example, G.M. Blackburn, M.J. Parratt, J. Chem. Soc., Per-kin Trans 1 (1986), 1425; G.M. Rosolapoff, J.S. Powell, J.
Am. Chem. Soc. 72 (1950), 4198; R.M. Keenan et al., J. Med.
Chem. 3S (1992), 3858; H. Ahlbrecht, W. Farnung, Synthesis 336 (1977); E. D'Incan, J. Seyden-Penne, Synthesis, 516 (1975); S. Hanessian, Y.L. Benn~ni~ D. Delorme, Tetrahedron Lett. 31 (1990), 6461}:
~-1 Ar - CH2 ~Br + Rf - CH2 - " y2Rl strong (I base _ XVII XVI y3R2 Rf yl I~X ehtlhane Y C CY4 aikyl-, Ar CH2 - 1H - ~_ Y2R1 (Cl-C4-alkoxy)carbonyl- or di-(Cl-C4-alkyl)amino- y3R2 subst. ethanediyl~
As regards the definition of Ar, see process A.l;
Rf is hydrogen, cyano, halogen, Cl-C4-alkyl, (Cl-C4-alkoxy)carbonyl or di(Cl-C4-alkyl)amino (XVIa = XVI where Rf - CN; XVIb = XVI where Rf = alkyl).
Examples of suitable strong bases are sodium hydroxide, - butyllithium and lithium diisopropylamide.
The process is usually carried out in an inert organic sol-vent, preferably in an aromatic hydrocarbon such as toluene or a cyclic ether such as tetrahydrofuran.
The process is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably from (-78)~C to 25~C.
Those phosphonic acid derivatives XVI and benzyl halides XVII which are not already known can be prepared in a ~nner known per se.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 A.ll) by reacting phenylacetaldehydes XVIII with dialkyl phos-phites XIII, if desired in the presence of ammonia or of a primary or secondary amine {cf. in this context, for example, M.E. Ch~lm~rs, G.M. Kosolapoff, J. Am. Chem. Soc.
75 (1953), 5278; C. Li, C. Yuan, Tetrahedron Lett. 34 (1993), 1515}:
OH O
10 Ar - CH2 CHO 3 Ar - CH2 1H - - O ( C1-C4_a1kY1 ) (XVIII) O(Cl-C4-alkyl) I ~ Eth = hydroxyethylene; yl~y2~y3 =
,~ O
XVIII +XIIINH3(c C( alk4yl) Y~ Ar CH~ 7H 7 - O(Cl-C4-alkyl) (H/Cl-C4-alkyl)2N O(Cl-C4-alkyl) ( Eth = -CH2-CH(NH2)-~ ) I ~ -CH2-CH[NH(Cl-C4-alkyl)~
~ -CH2-CH [ N(Cl-C4-alkyl) 2 ~ _; yl, Y2, y3 = O>
As regards the definition of Ar, see process A.l).
Examples of suitable solvents are water, the lower alcohols such as methanol, ethers such as tetrahydrofuran and die-thyl ether, and pyridine.
The process is generally carried out at from (-100)~C to the boiling point of the reaction mixture, preferably from 20 to 50~C.
Those phenylacetaldehydes XVIII which are not already known can be prepared in a m~nn~r known per se.
A.12) by reacting alkyl h~ es XIX with trialkyl phosphites XII
in a l'nn~r known per se following Arbuzov's method {see in this context, for example, A.Y. Garner, E.C. Chapin, P.M.
Scanlon, J. Org. Chem. 24 (1959), 532}:
- ~ 0050/46S86 CA 0224~6~9 1998-08-06 .
Ar - CR CH2 ~3r + XII
IJ
O
H/Cl-C4--alkyl Ar CH CH2 - ~'- O(Cl-C4-alkyl XIX
~_ O(Cl-C4-alkyl) H/Cl-C4-alkyl I ~ Eth = -cH2-cH2 -cH(cl-c4-alkyl)-cH2-; yl~y2~y3 =
, As regards the definition of Ar, see process A.1).
The reaction is preferably carried out in the absence of a solvent, suitable reaction t~reratures being from 0~C to the boiling point of the trialkyl phosphite XII, preferably from 20 to 150~C.
Those alkyl hA 1; ~S XIX which are not already known can be prepared in a m~nnPr known per se.
A.13) by reacting an aldehyde VIa with a trichloromethanephos-phonic acid derivative XXVI in the presence of an alkyl-lithium compound XXVII
yl ll (Cl-C4-alkyl)-Li Ar- CH0 + C13C p__ Y2Rl ~ I~X = -CH=C(Cl)-~
VIa I XXVII
y3R2 XXVI
As regards the definition of Ar, see process A.1).
Normally, the trichloromethanephosphonic acid derivative XXVI is first reacted with the alkyllithium compound XXVII
in an inert organic solvent, for example an ether such as tetrahydrofuran or a hydrocarbon such as n-hexane. The process is generally carried out between the melting point - ~ 0050/46586 CA 0224~6~9 1998-08-06 .
and the boiling point of the reaction mixture, preferably at from (-80) to (-50)~C.
The reaction product is then reacted with the aldehyde VIa - preferably without prior work-up -, the reaction temperature preferably being raised to approximately +20~C.
B) Derivatization of substituted aromatic phosphoric acid derivatives of the formnl~ I
As regards the reaction procedure and the ratios of the reactants, reference may be made, for example, to Houben-Weyl, Methoden der Organischen Chemie tMethods in Organic Ch~-ictry]~ Georg Thieme Verlag, Stuttgart, Vol. 12/1, 4th Edition 1963, p. 387 et seq., 407 et seq. and 557 et seq.;
~r Vol. E2 1982, p. 300 et seq. and 419 et seq.
B.l) Hydrogenation of substituted aromatic phosphonic acid derivatives I where Eth is ethene-1,2-diyl or a halogen-substituted ethane-1,2-diyl bridge {cf., for example, C.N.
Robinson, P.K. Li. J.F. Addison, J. Org. Chem. 37 (1972), 2939; G.T. Lowen, M.R. Almo~, J. Org. Chem. 59 (1994), 4548}:
I~Eth= unsubst. or subst. 1,2- I{Eth=unsubst. or eth~ne~iyl or chlorine-, subst.
bromine- or io~i ne - 1,2-ethane-substituted 1,2-ethane ' ~ ' diyl}
diyl, to which further subst. may be attached if desired~
'~' ' As regards the definition of Ar, see process A.1).
The hydrogenation is carried out either using hydrogen in the presence of a catalyst customary for this purpose, such as palladium or platinum on active charcoal or Raney nickel, at from 0 to 150~C and a hydrogen pressure of approximately 1 to 200 bar, or using a metal hydride such as sodium borohydride and lithium alu~in-lm hydride, at from 0~C to the boiling point of the reaction mixture.
Examples of solvents which are suitable for the hydrogena-tion using hydrogen are water, the lower alcohols, such as methanol and ethanol, ethers such as diethyl ether and tetrahydrofuran or esters such as ethyl acetate.
0050/46586 CA 0224~6~9 1998-08-06 . 125 When reacting the starting compound with a metal hydride, ~ the process is preferably carried out in an inert organic solvent, in particular an ether such as diethyl ether and tetrahydrofuran.
B.2) Hydrolysis of substituted aromatic phosphonic acid deriva-tives I, conversion of the process products into phosphonyl halides, and reaction thereof with nucleophiles:
O
hydro- ¦
Ar- Eth- ORl i~ Ar- Eth- o~ 3 Ar- Eth- ~-Cl-~ -I{Y1=O}
oR2 OH Cl lS I {yl,y2,Y3 = O} I {Yl,Y2,Y3=o;Rl,R2=H} XXIVa C hydrolysis ~
O
Ar- Eth-.'- oRl Ar - Eth - ~--oR1 ~ I {yl,y2=O}
OH Cl I {yl,y2,Y3=O; R2=H} XXVa ~,S S
Ar- Eth- ~- Cl- ~- XXIVa-~ -Ar- Eth-. ORl ~ Ar - X -.'-30Cl OH Cl XXIVb I {Y=S;Y2,Y3=o;R2=H} XXVb ~ ~
I {Yl=S} I {Yl=S; y2=o}
40As regards the definition of Ar, see process A.l).
.
In this process, the substituted aromatic phosphonic acidderivatives I are first cleaved hydrolytically (acidic or basic) or, in the event that Rl and/or R2 is a benzyl or allyl radical, also hydrogenolytically to give phosphonic acids and phosphonic monoesters I. If desired, the cleavage can also be carried out by means of reaction with a . ~ 0050/46586 CA 0224~6~9 1998-08-06 .
tri(Cl-C4-alkyl)silyl halide, such as chlorotrimethyl-silane, iodotrimethylsilane, or a mixture of chlorotri-methylsilane and an alkali metal iodide.
The cleaved products can then be converted into the corre-sponding phosphonylmono- or -dichlorides XXIVa and XXVa by reacting them with a halogenating agent such as oxalyl chloride, thionyl chloride or phosphorus pentachloride.
If desired, the phosphonyl dichlorides XXIVa can be sulfur-ized in a ~nner known per se using a sulfurizing agent, such as phosphorus(V) sulfide and 2,4-bis(4-methoxyphe-nyl)-1,3,2,4-di~h;~;rhosphetane-2,4-dithione ("Lawesson~s reagent") to give thionophosphonyl dichlorides XXIVb. As regards suitable solvents, t~mr~rature and ratios, mention may be made of what has been said in DE-A 19 504 188 under process D).
~Finally, other substituted aromatic phosphonic acid deriva-tives I are accessible by reacting XXIV and XXV with nucleophiles HY2Rl or HY3R2.
The phosphonic acid monoester chlorides XXVa can be con-verted into the thionophosphonic acid monoesters XXVb, for ex_mple by reaction with sodium hydrogen sulfide.
B.3) El;~;nAtion of hydrogen halide from compounds I where Eth = -CH2-CH(halogen)- or -CH=C(halogen)-:
C I {Eth z -CH2-CH(halogen)-} i I {Eth = -CH=CH-}
I {Eth 5 -CH=C(halogen)-} base I {Eth = -C~C-}
The process is normally carried out in water or an inert organic solvent, e.g. an alcohol such as ethanol, an ether such as diethyl ether, tetrahydrofuran and dioxane, or an aprotic solvent such as acetonitrile, dimethylformamide and dimethyl sulfoxide.
Examples of suitable bases are A lk~l; metal hydroxides, alkali metal carbonates, alkali metal hydrides, alkyllithium compounds such as butyllithium, or organic amines such as triethylamine, . ~ 0050/46586 CA 0224~6~9 l998-08-06 1,4-diazabicyclot2.2.2.]-octane (DABC0) and 1,8-diazabicyclor5.4Ø]undec-7-ene (DBU).
As a rule, the reaction is carried out at from (-100)~C to the boiling point of the reaction mixture, preferably at from 20 to 100~C.
C) Synthesis of the heterocycles Rs:
10 C.1) Synthesis of the triazolopyridine ring ~ NH H2N - ~H yl 15 R24 - N + R4 ~ Eth - P - y - o - (Cl-C4-alkyl) R3 Y3R2 XXIX XXVIII
N ~\ ~ base y o NH yl (Cl-C4-alkyl) R4 ~ Eth - p - y2Rl XXX
acid C
I (R~ = ~7 In this process, an amidine of the formula XXIX or an acid addition salt thereof (for example the hydrochloride, hydrobromide or hydrogen sulfate thereof) is reacted with a phenylhydrazine of the formula XXVIII or an acid addition salt thereof (for example the hydrochloride, hydrobromide or hydrogen sulfate thereof) in the presence of a base, for example an A1k~li metal acetate, alkali metal hydrogen carbonate, alkali metal carbonate or alkali metal hydroxide or a tertiary amine such as triethylamine.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 As a rule, the reaction is carried out in an inert organic solvent, e.g. an ether such as tetrahydrofuran, an alcohol such as ethanol, or an aprotic solvent such as dimethylformamide, acetonitrile or dimethyl sulfoxide.
As a rule, the reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 50~C.
The reaction product XXX is then cyclized in an inert organic solvent! e.g. a hydrocarbon such as toluene or n-hexane, an ether such as tetrahydrofuran, an alcohol such as ethanol, a carboxylic acid such as acetic acid, or an aprotic solvent such as dimethylform~m;~, acetonitrile or dimethyl sulfoxide, in the presence of an acid, for example acetic or hydrochloric acid.
. . .
Again, the cyclization is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
C.l.l)Preparation of the phenylhydrazines XXVIII from Anilines of the formula XXXI:
E~2N yl ~ ll 1) diazotization R4 ~ / \ ~ Eth - P - Y2R1 3 XXVIII
~ 1 2) reduction 30 \ y3R2 R
C XXXI
In this process, the aniline XXXI is first diazotized. In this context, reference may be made to the information given above for A.1).
The resulting diazonium salt is reacted with a reducing agent, for example a tin(II) compound such as tin(II) chloride in an inert solvent/diluent, e.g. a hydrocarbon such as toluene or n-he~ne, an ether such as tetrahydrofuran, an alcohol such as ethanol, an acid such as acetic acid and hydrochloric acid, an aprotic solvent such as dimethylforr-~;de, acetonitrile and dimethyl - sulfoxide, or in water. The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 Especially preferred phenylhydrazines of the form~ XXVIII
are listed in Table 2 below.
Table 2 H2N NH yl R4 ~ Eth P y2Rl XXVIII
No. R3 R4 -Eth-P(=yl)(y2Rl)(y3R2) XXVIII.l Cl H -CH2-CH2-P(=O)(OCH3k XXVIII.2 Cl Cl -CH2-CH2-P(=0)(0CH3)z XXVIII.3 Cl F --CH2-CH2--P(=0)(0CH3k XXVIII.4 Cl H -CH2-CH2-P(=O)(OC2Hs)2 XXVIII.5 Cl Cl -CH2-CH2-P(=O)(Oc2Hs)2 XXVIII.6 Cl F -CH2-CH2-P(=O)(OC2Hs)2 XXVIII.7 Cl H -CH2-CH(Cl)--P(=O)(OCH3)2 2 5 xxvm.8 Cl Cl -CH2-CH(Cl)--P(=O)(OCH3)2 XXVIII.9 Cl F --CH2-CH(Cl)--P(=O)(OCH3)2 XXVIII.10 Cl H -CH2-CH(Cl)--P(=o)(oc2Hs)2 XXVIII.ll Cl Cl -CH2-CH(Cl)--P(=O)(OC2Hs)2 XXVm.12 Cl F --CH2--CH(Cl)--P(=O)(OC2Hs)2 XXVIII.13 Cl H -CH2-CH(Br)-P(=O)(OCH3)2 C ~VIII.14 Cl Cl -CH2-CH(13r)-P(=O)(OCH3)2 XXVIII.lS Cl F -CH2-CH(Br)-P(=O)(OCH3)2 3 5 XXVIII. 16 Cl H -cH2--cH(Br)-p(=o)(oc2Hs)2 XXVIII.17 Cl Cl -CH2-CH(I3r)-P(=O)(OC2Hs)2 XXVIII. 18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2 XXVIII.l9 Cl H -CH2-CH(CN)-P(=O)(OCH3)2 XXVIII.20 Cl Cl --CH2-CH(CN)-P(=O)(OCH3)2 XXVIII.21 Cl F -CH2-CH(CN)--P(=O)(OCH3)2 XXVIII.22 Cl H --CH2-CH(CN)--P(=O)(Oc2Hs) ~VIII.23 Cl Cl -CH2-CH(CN)-P(=O)(OC2Hs) XXVIII.24 Cl F -CH2-CH(CN)-P~=O)(OC2Hs) XXVIII.25 Cl H --CH=CH-P(=O)(OC~)2 XXVIII.26 Cl Cl -CH=CH-P(=O)(OCH3)2 - ~0050/46586 CA 02245659 l998-08-06 .
No. R3 R4 -E~-P(=yl)(y2Rl)(y3R2)~X~II.27 Cl F -cH=cH-p(=o)(ocH3)2 ~X~II.28 Cl H -CH=CH--P(=o)(oc2Hs)2 5~XVIII.29 Cl Cl -CH=CH - P(=O)(OC2Hs)2 ~X~II.30 Cl F -CH=CH--P(=O)(OC2Hs)2 ~XVI~.31 Cl H -CH=C(CI)-P(=O)(OCH3)2 ~X~nlI.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 10~X~II.33 Cl F -CH=C(CI)-P(=O)(OCH3)2 II.34 Cl H -CH=C(CI)-P(=O)(OC2Hs)2 ~VD~.35 Cl Cl -CH=C(Cl)--P(=o)(oc2Hs)2 ~Y~II.36 Cl F -CH=C(Cl)--P(=O)(OC2Hs)2 15~X~II.37 Cl H -CH=C~Br)-P(=O)(OCH3)2 ~VI~.38 Cl Cl -CH=C~Br)-P(=O)(OCH3)2 ~XVIU.39 Cl F -cH=c~Br)-p(=o)(ocH3)2 ~XV~II.40 Cl H- -CH=C~Br)-P(=O)(OC2H5)2 20~XVIII.41 Cl Cl -CH=C~Br)-P(=O)(OC2Hs)2 ~XVI~.42 Cl F -cH=c~Br)-p(=o)(oc2Hs)2 ~XVIII.43 Cl H -CHSC(CN~-P(=0)(OCH3)2 ~XVD~.44 Cl Cl --CH=C(CN~-P(=O)(OCH3)2 25~XVD~.45 Cl F -CH=C(CN~--P(=O)(OCH3)2 ~XVIL46 Cl H -CH=C(CN~--P(=o)(oc2Hs)2 ~XVI~.47 Cl Cl -CH=C(CN~-P(=O)(OC2Hs)2 ~YVI~.48 Cl F -CH=C(CN~-P(=O)(OC2Hs)2 30 C.1.2)Preparation of the ~n;l;nes XXXI by reducing nitrobenzene derivatives XXXII:
.
~'_.- 02N yl ~ ll reduction 35 R4 ~ / \ ~ Eth P Y2R1 3 XXXI
\=~ I
XXXII
The reduction can be carried out with a metal such as iron, zinc or tin under acidic reaction conditions, or with a complex hydride such as lithiumaluminum hydride and sodium borohydride, examples of solvents being water, alcohols such as methanol, ethanol and isopropanol, or ethers such as diethyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran and ethylene glycol dimethyl ether, depending on the chosen reducing agent.
- , 0050/46586 CA 0224~6~9 1998-08-06 If the reduction is carried out with a metal, this is preferably performed in the absence of a solvent in an inorganic acid, in particular in concentrated or dilute hydrochloric acid, or in an organic acid such as acetic acid. However, it is also possible to admix an inert solvent, e.g. one of those mentioned above, with the acid.
The amount of acid is not critical. In order to reduce the starting compound as completely as possible, it is expedient to use at least an equivalent amount of acid.
The reaction temperature is generally at from (-30) to 200~C, preferably at 0 to 80~C.
The nitro group of the compounds XXXII may also be ~~ hydrogenated catalytically using hydrogen. Examples of - catalysts which are suitable for this purpose are Raney nickel, p~ ;um-on-charcoal~ palladium oxide, platinum and platinum oxide, an amount of catalyst of from 0.05 to 10.0 mol% based on the compound to be reduced generally being sufficient.
The process is either carried out in the absence of a solvent or in an inert solvent or diluent, e.g. in acetic acid, a mixture of acetic acid and water, ethyl acetate, ethanol, or in toluene.
After the catalyst has been ~ ,ved, the reaction solution can be worked up as usual to give the product.
~' The hydrogenation can be carried out under atmospheric pressure or under elevated pressure.
Especially preferred ~n; lines XXXI are listed in Table 3 below.
Table 3 H2N yl R4 _ ~ Eth - P - y2Rl XXXI
R3 y3R2 No. R3R4 -Eth-p(=yl)(y2Rl)(y3R2) X~.l Cl H -CH2-CH2--P(=O)(OCH3)z X~I.2 Cl Cl -CH2-CH2--P(=O)(OCH3)2 X~I.3 Cl F -CH2-CH2-P(=O)(OCH3)2 X~I.4 Cl H -CH2-CH2--P(=~)(~C2Hs)2 X~I.S Cl Cl -CH2-CH2-P(=O)(Oc2Hs)2 X~.6 . Cl F -cH2-cH2-p(=o)(oc2Hs)2 X~.7 Cl H -CH2-CH(Cl)--P(=O)(OCH3)2 X~I.8 Cl Cl -CH2-CH(Cl)-P(=O)(0CH3)2 X~.9 Cl F -CH2-CH(Cl)-P(=O)(0C~3)2 X~I.10 Cl H -CH2-CH(Cl)--P(=O)(OC2Hs)2 XXXI.ll Cl Cl -CH2-CH(Cl)--P(=o)(oc2Hs)2 X~.12 Cl F -cH2-cH(cl)-p(=o)(oc2H5)2 f X~I.13 Cl H -CH2-CH(Br)-P(=O)(OCH3)2 X~.14 Cl Cl -cH2-cH(Br)-p(=o)(ocH3)2 XXXI.lS Cl F -CH2-CH(Br)-P(=O)(OCH3)2 X~I.16 Cl H -cH2-cH(Br)-p(=o)(oc2Hs)2 X~. 17 Cl Cl -cH2-cH(Br)-p(=o)(oc2Hs)2 X~I.18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2 XXXI.l9 Cl H -CH2--CH(CN)-P(=O)(OCH3)2 X~.20 Cl Cl -CH2--CH(CN)-P(=O)(OCE~)2 X~I.21 Cl F -CH2-CH(CN)-P(=O)(OCH3)2 X~.22 Cl H -CH2--CH(CN)-P(=O)(OC2Hs)2 X~.23 Cl Cl -CH2-CH(CN)-P(=O)(OC2Hs)2 X~I.24 Cl F -cH2-cH(cN)-p(=o)(oc2H5)2 ~- X~.25 Cl H -CH=CH-P(=O)(OCE~3)2 X~.26 Cl Cl -CH=CH-P(=O)(OCH3)2 X~.27 Cl F --CH=CH-P(=O)(OC~3)2 X~I.28 Cl H -CH=CH-P(=O)(OC2Hs)2 X~.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~I.30 Cl F -CH=CH--P(=o)(oc2Hs)2 X~.31 Cl H -CH=C(Cl)-P(=O)(OC~3)2 XX~.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 X~.33 Cl F -CH=C(Cl)--P(=O)(OCH3)2 X~.34 Cl H -CH=C(Cl)-P(=O)(OC2Hs~2 X~I.35 Cl Cl -CH=C(Cl)-P(=O)(OC2Hs)2 X~I.36 Cl F -CH=C(Cl)-P(=O)(OC2Hs)2 XXXI.37 Cl H -cH=c(Br)-p(=o)(ocH3)2 - ~ 0050/46586 CA 0224~6~9 1998-08-06 No. R3 R4 -Eth-P(=Yl)(Y2Rl)(Y3R2) X~I.38 Cl Cl -cH=c(Br)-p(=o)(oc~3)2 X~.39 Cl F -CH=C(13r)-P(=O)(OC~)2 XXXI.40 Cl H -cH=c(Br)-p(=o)(oc2Hs)2 X~.41 Cl Cl -CH=C(Br)-P(=O)(OC2Hs)2 X~I.42 Cl F -CH=C(Br)-P(=O)(OC2Hs)2 ~.43 Cl H -CH=C(CN)--P(=O)(OC~)2 ~.44 Cl Cl -CH=C(CN)-P(=O)(OC~)2 X~I.45 Cl F -CH=C(CN)-P(=O)(Oc~)2 X~I.46 Cl H -CH=C(CN)--P(=O)(OC2H~)2 X~.47 Cl Cl -CH=C(CN)-P(=O)(OC2H5)2 X~.48 Cl F -CH=C(CN)-P(=O)(OC2Hs)2 ( C.1.3)Preparation of the nitrobenzene derivatives XXXII:
yl ll nitration R4 ~ Eth P y2R1 3 XXXII
\=< I .
~XXlll Examples of suitable nitrating reagents are nitric acid in various concentrations, also concentrated and fuming nitric acid, mixtures of sulfuric acid and nitric acid, acetyl nitrates and alkyl nitrates.
The reaction can be carried out either in the absence of a C solvent in an excess of the nitrating reagent or in an inert solvent or diluent, suitable examples being water, mineral acids, organic acids, halohydrocarbons such as methylene chloride, anhydrides such as acetic anhydride, and mixtures of these solvents.
Starting compound XXXIII and nitrating reagent are expediently employed in approximately equimolar amounts;
however, to optimize conversion of the starting compound it may be advantageous to use the nitrating reagent in an excess of up to approximately 10 times the molar amount. If the reaction is carried out without solvent in the nitrating reagent, the latter is present in an even larger excess.
- ~ 0050/46586 CA 02245659 l998-08-06 The reaction t~mrerature is norm~lly at from (-100) to 200~C, preferably (-30) to +50~C.
Especially preferred nitro compounds of the formula XXXII
are listed in Table 4 below.
Table 4 ~2~ yl R4 ~ Eth P y2Rl XXXII
f- No. R3 R4 -E~-P(=y~)~2Rl)~3R2) ~ ~XXII.1 Cl H -cH2-cH2-p(=o)(ocH3)2 ~XXII.2 Cl Cl -CH2-CH2-P(=O)(OCH3)2 20~ .3 Cl F -CH2--CH2--P(=O)(OCH3)2 ~YXII.4 Cl H -cH2-cH2-p(=o)(oc2Hs)2 ~X~I.5 Cl Cl -CH2-CH2-P(=O)(OC2Hs)2 X~U.6 Cl F -cH2-cH2-p(=o)(oc2H5)2 25X~YU.7 Cl H --CH2--CH(Cl)-P(=O)(OCH3)2 X~YU.8 Cl Cl -CH2-CH(Cl)-P(-O)(OCH3)2 9 Cl F --CH2--CH(Cl)-P(=O)(OCH3)2 ~ L10 Cl H -cH2-cH(cl)-p(=o)(oc2Hs)2 30~YXII.11 Cl . Cl -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~U.12 Cl F -CH2-CH(Cl)-P(=O)(OC2Hs)2 U.13 Cl H -CHz-CH~Br)-P(=O)(OCH3)2 ~ .14 Cl Cl -CH2-CH ~r~p(=o)(ocH3)2 35~ .15 Cl F -CH2-CH ~r)-P(=O)(OCH3)2 X~ .16 Cl H -CH2-CH ~r)-P(=O)(OC2Hs)2 ~XXII.17 Cl Cl -cH2-cH~Br)-p(=o)(oc2Hs)2 ~XXII.18 Cl F -cH2-cH~Br)-p(=o)(oc2Hs)2 40~ .19 Cl H -CH2-CH(C ~ -P(=O)(OCH3)2 .20 Cl Cl -CH2-CH(CN~-P(=O)(OcH3)2 ~XXII.21 Cl F --CH2-CH(CN~-P(=0)(OCH3)2 , ~XXII.22 Cl H -CH2-CH(CN~-P(=O)(OC2Hs)2 45~XII.23 Cl Cl -CH2-CH(C ~-P(=O)(OC2H5)2 ~XXII.24 Cl F -CH2-CH(CN~-P(=0)(OC2Hs)2 - ~ 0050/46586 CA 02245659 lgs8-08-06 No. R3 R4 -Eth-p(=yl)(y2Rl)(y3R2) X~I.25 Cl H -CH=CH-P(=O)(OCH3)2.
X~II.26 Cl Cl -CH=CH-P(=O)(0CH3)2 X~I.27 Cl F -CH=CH-P(=0)(0CH3)2 X~II.28 Cl H -CH=CH-P(=0)(0C2H5)2 X~I.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~I.30 Cl F -CH=CH-P(=O)(OC2H5)2 X~.31 Cl H -CH=C(Cl)-P(=0)(0CH3)2 ~II.32 . Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 X~II.33 Cl F -CH=C(Cl)--P(=O)(OCH3)2 X~.34 Cl H -CH=C(Cl)--P(=O)(OC2H5)2 X~I.35 Cl Cl -CH=C(Cl)-P(=O)(OC2H5)2 X~II.36 Cl F -CH=C(Cl)-P(=0)(0C2H5)2 X~I.37 Cl H -CH=C(Br)-P(=O)(OCH3)2 X~I.38 Cl Cl -CH=C(Br)-P(=O)(OCH3)2 X~I.39 Cl F -CH=C(Br)-P(=O)(OCH3)2 X~I.40 Cl H -cH=c(Br)-p(=o)(oc2H5)2 X~I.41 Cl Cl -CH=C(Br)-P(=O)(OC2H5)2 X~II.42 Cl F -cH=c(Br)-p(=o)(oc2H5)2 X~.43 Cl H -CH=C(CN)-P(=O)(OCH3)2 ~II.44 Cl Cl -CH=C(CN)-P(=O)(OCH3)2 X~.45 Cl F --CH=C(CN)-P(=O)(OCH3)2 XX~I.46 Cl H --CH=C(CN)-P(=O)(OC2H5)2 ~I.47 Cl Cl --CH=C(CN)--P(=o)(oc2Hs)2 X~II.48 Cl F -CH=C(CN)-P(=0)(0C2H5)2 C C.1.4)Preparation of the aromatic phosphonic acid derivatives XXXIII where Eth is -CH=C(Cl)-:
yl Il (Cl-C4-alkyl)-Li R4 ~ CH0 + C13C - P Y2R3 i XXXIII
~ I XXVII
R3 y3R2 XXXIV XXVI
As regards this reaction, reference may be made to the information given above under A.13).
- 0050/46586 CA 02245659 l998-08-06 Especially preferred aromatic phosphonic acid derivatives of the for~ XXXIIIa (= XXXIII where R4 ; R4 = halogen) are listed in Table 5 below.
Table 5 yl R4~ ~ Eth - P y2Rl xxxTTTa No. R3 R4 -Eth--p(=yl)(y2Rl)(y3R2) 15X~.l Cl Cl -CH2--CH2--P(=o)(ocH3)2 x~m.2 Cl F -CH2--CH2--P(=O)(OCH3)2 f X~III.3 Cl Cl . -CH2--CH2-P(=O)(OC2Hs)2 x~m.4 Cl F --CH2--CH2--P(=O)(OC2H5)2 X~III.5 Cl Cl --CH2--CH(Cl)--P(=O)(OCH3)2 20.6 Cl F --CH2--CH(Cl)--P(=O)(OCH3)2 x~m-7 Cl Cl --CH2-CH(Cl)--P(=o)(oc2Hs)2 X~III.8 Cl F -cH2--CH(cl)-P(=O)(Oc2Hs)2 X~I.9 Cl Cl -cH2-cH(Br)-p(=o)(ocH3)2 25.10 Cl F -cH2-cH(Br)-p(=o)(ocH3)2 X~II.ll Cl Cl -CH2-CH(Br)-P(=O)(oc2Hs)2 X~III.12 Cl F -CH2--cH(Br)-p(=o)(oc2Hs)2 X~II.13 Cl Cl -CH2--CH(CN)-P(=O)(OCH3)z X~III.14 Cl F -cH2--CH(CN)--P(=O)(OCH3)2 X~.15 Cl Cl -CH2--CH(CN)-P(=O)(OC2Hs)2 C X~III.16 Cl F -CH2--CH(CN)-P(=O)(OC2Hs)2 X~III.17 Cl Cl -CH=CH-P(=O)(OCH3)2 X~m.18 Cl F -CH=CH-P(=O)(OCH3)2 X~III.l9 Cl Cl -CH=CH-P(=O)(OC2Hs)2 X~.20 Cl F --CH=CH-P(=O)(OC2Hs)2 X~II.21 Cl Cl -CH=C(Cl)--P(=O)(OCH3)2 X~III.22 Cl F -CH=C(Cl)-P(=O)(OCH3)2 X~III.23 Cl Cl -CH=C(Cl)--P(=O)(OC2Hs)2 X~II.24 Cl F --CH=C(Cl)-P(=O)(OC2Hs)2 X~II.25 Cl Cl --CH=C(Br)-P(=O)(OCH3)2 45XXXIII.26 Cl F -CH=C(Br)-P(=O)(OCH3)2 X~.27 Cl Cl -cH=c(Br)-p(=o)(oc2Hs)2 CA 02245659 l998-08-06 137 _ No. R3 R4 -Eth-P(=yl)(y2Rl)(y3R2) x~m.28 Cl F --CH=C(Br)--P(=O)(OC2Hs)2 ~II.29 Cl Cl -CH=C(CN)-P(=O)(OC~3)2 X~II.30 Cl F --CH=C(CN)-P(=O)(OC~3)2 X~II.31 Cl Cl --CH=C(CN)--P(=O)(OC2Hs)2 X~III.32 Cl F --cH=c(cN)-P(=O)(Oc2Hs)2 10 C.2) Synthesis of the thiazole ring S~ f N R50 O HN yl I R5l R4 ~ / \ ~ Eth P - y f~ ~ ~ I
- Cl/Br/I / \ \R3 Y3R2 XXXVI / \ XXXV
~ Rsl / base S N- R50 r N yl I ~ R5 = ~20 ~ 11 ~
R4~ Eth - p - y2Rl \= ~ 3 2 dehydration - XXXVII
In this process, a thiourea derivative of the formula XXXV
is reacted with a ketone of the formula XXXVI in the presence of a base, for example an alkali metal acetate, alkali metal hydrogen carbonate, ~lkAl; metal carbonate, A 1 k5~1i metal hydroxide or a tertiary amine such as triethylamine.
The process is normally carried out in an inert solvent/
diluent, e.g. in a hydrocarbon such as toluene and n-hexane, an ether such as tetrahydrofuran, or in an aprotic solvent such as dimethylfor~-m;~, acetonitrile and dimethyl sulfoxide.
CA 0224~659 1998-08-06 The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 1-50~C.
This process results in the direct formation of either the compounds of the formula I where R5 = ~20 or alcohols of the formula 2~15.X.Vll which can be dehydrated in the customary manner to give I, for example by azeotropic distillation with a suitable entraining agent, e.g. toluene or xylene, or by reaction with catalytic amounts of a strong acid such as hydrochloric acid, sulfuric acid and toluenesulfonic acid, or by esterification with a carboxylic acid chloride, sulfonic acid chloride, carboxylic anhydride or sulfonic anhydride and treatment with a base, for example an ~lk~li metal acetate, ~lk~l; metal hydrogen carbonate, Alki~l;
metal carbonate, alkali metal hydroxide or a tertiary amine f such as triethyl~m; ne and pyridine.
C.2.1)Preparation of the thiourea derivatives XXXV by reaction of isocyanates XXXVIII with ~n; 1 ;nes XXXI:
H2N yl SCN Rso ~ R4 ~ Eth - p Y2Rl ~ XXXV
~
xxxvllI \ y3R2 R
XXXI
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n- h~ne, halogenated hydlocarbons such as dichloromethane, ethers such as tetrahydrofuran, alcohols such as ethanol, aprotic solvents such as dimethylfor~- i~e, acetonitrile and dimethyl sulfoxide.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
Especially preferred thiourea derivatives of the formula XXXV are iisted in Table 6 below.
- ~ 0050/46586 CA 02245659 l998-08-06 Table 6 H
S~f N R50 HN yl R4~ Eth- F Y R
y3R2 No. R3 R4 Rso -Eth-P(=Yl)(Y2Rl)(Y3R2) X~V.l Cl H CH3 -CH2-CH2-P(=O)(OcH3)2 X~V.2 Cl Cl CH3 -CH2-CH2-P(=O)(OcH3)2 X~V.3 Cl F CH3 -CH2-CH2-P(=O)(OCH3)2 X~V.4 Cl H CH3 -CH2-CH2-P(=O)(OC2H5)2 X~V.S Cl Cl CH3 -CH2--CH2-P(=O)(OC2Hs)2 X~V.6 Cl F CH3 -CH2-CH2-P(=O)(OC2H5)2 XXXV.7 Cl H CH3 -CH2-CH(Cl)-P(=O)(OcH3)2 XX~V.8 Cl Cl CH3 -CH2-CH(Cl)--P(=O)(OCH3)2 X~V.9 Cl F CH3 -CH2-CH(Cl)-P(=O)(OCH3)2 X~V.10 Cl H CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V. 11 Cl Cl CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V.12 Cl F CH3 -CH2-CH(Cl)-P(=O)(OC2Hs)2 X~V.13 Cl H CH3 -CH2-CH(Br)-P(=O)(OCH3)2 ~V.14 Cl Cl CH3 -cH2-cH(Br)-p(=o)(ocH3)2 X~V.15 Cl F CH3 -CH2-CH(Br)-P(=O)(OCH3)2 ~- XXXV.16 Cl H CH3 -cH2-cH(Br)-p(=o)(oG2H5)2 XXXV.17 Cl Cl CH3 -CH2-CH(Br)-P(=O)(OC2Hs)2 35 X~V.18 Cl F CH3 -CH2-CH(Br)-P(=O)(Oc2Hs)2 XXXV 19 Cl H CH3 -cH2-cH(cN)-p(=o)(ocH3)2 X~V20 Cl Cl CH3 -CH2-CH(CN)-P(=O)(OCH3)2 X~V.21 Cl F CH3 -CH2-CH(CN)-P(=O)(OcH3)2 40 X~V22 Cl H CH3 -CH2--CH(CN)-P(=O)(OC2Hs)2 XXXV 23 Cl Cl CH3 -CH2-CH(CN)-P(=O)(OC2Hs)2 X~V.24 Cl F CH3 -CH2--CH(CN)-P(=O)(OC2Hs)2 X~V.25 Cl H CH3 --CH=CH--P(=O)(OC~3)2 45 X~V.26 Cl Cl . CH3 -CH=CH-P(=O)(OCH3)2 XXXV.27 Cl F CH3 -CH=CH-P(=O)(OCH3)2 - ,0050/46586 CA 022456~9 lss8-08-06 .
No. R3 R4 Rso -Eth-P(=Yl)(Y2Rl)(Y3R2) XXXV.28 Cl H CH3 -CH=CH-P(=O)(OC2Hs)2 X~V.29 Cl Cl CH3 -cH=cH-p(=o)(oc2Hs)2 5 X~V.30 Cl F CH3 -CH=CH-P(=O)(OC2Hs)2 X~V.31 Cl H CH3 --CH=C(Cl)--P(=O)(OCH3)z XXXV.32 Cl Cl CH3 -CH=C(Cl)-P(=O)(Oc~3)2 X~V.33 Cl F . CH3 -CH=C(Cl)--P(=O)(ocH3)2 lo XXXV34 Cl H CH3 --CH=C(Cl)--P(=O)(Oc2Hs) ~V.35 Cl Cl CH3 -CH=C(Cl)-P(=O)(OG2Hs) X~V.36 Cl F CH3 -CH=C(Cl)--P(=O)(Oc2Hs) X~V.37 Cl H CH3 -CH=C(Br)-P(=O)(OCH3)2 15 XXX~.38 Cl Cl CH3 -cH=c(Br)-p(=o)(ocH3)2 XX~V.39 Cl F CH3 -CH=C(13r)-P(=O)(Oc~3)2 f XXXV.40 Cl H CH3 -CH=C(13r)-P(=O)(OC2Hs) X~V.41 Cl Cl CH3 -CH=C(Br)-P(=O)(OG2Hs) 20 XXXV.42 Cl F CH3 -CH=C(Br)-P(=O)(OC2Hs) XX~V.43 Cl H CH3 -CH=C(cN)-P(=O)(OcH3) X~V.44 Cl Cl CH3 --CH=C(CN)-P(=O)(OCH3) X~V.45 Cl F CH3 -CH=C(CN)-P(=O)(OCH3) 25 XXXV.46 Cl H CH3 --CH=C(CN)--P(=O)(OC2Hs) XXXV.47 Cl Cl CH3 -CH=C(CN)-P(=O)(OC2Hs) X~V.48 Cl F CH3 --CH=C(CN)-P(=O)(OC2Hs)2 30 C.3) Synthesis of the ~h;A~olopyridazine ring NH
~, coc12 R54'~ N ~
ClCOOCCl3 ~ ~ HN yl (C13C0)2CO ~ \>
R4 ~ ~ \~ Eth P y R
XXXIX
base I ~ R5 = ~21; Z3, z4 2 N}
- ~ 0050/46586 CA 0224~6~9 1998-08-06 .
In this process, a thiosemicarbazide derivative of the formula XXXIX is reacted with phosgene, diphosgene or triphosgene in the presence of a base - for example an A 1 kA 1; metal hydrogen carbonate, ~lk~l; metal carbonate, ~lk~l; metal hydroxide or a tertiary amine such as triethyl ~m; ne or pyridine.
The process is nor~l ly carried out in an inert solvent/
diluent, e.g. in a hydrocarbon such as toluene or n-he~ne, a halogenated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran, or in an aprotic solvent such as dimethylform~m;~, acetonitrile and dimethyl sulfoxide.
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at f from 0 to 150~.
C.3.1)Preparation of the thios~m;c~bazide derivatives XXXIX by reacting hydrazines XLI with isothiocyanates XL:
\ N yl ¦ + R4 ~ Eth - P Y2Rl ~ XXXIX
NH ~
/ R3 y3R2 XLI XL
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n-heY~ne, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran, alcohols such as ethanol or aprotic solvents such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
Especially preferred thiosemicarbazide derivatives of the formula XXXIX are listed in Table 7 below.
Table 7 - . OOSO/46586 CA 02245659 1998-08-06 .
142 _ N l~ S
5HN yl R4~ Eth p_ y2Rl XXXIX ~ RS3, R54 S ~ CH2 ~4 y3R2 lOR3 No. R3 R4 --Eth-P(=Yl)(Y2Rl)(Y3R2) - X~lX.l Cl H -CH2-CH2-P(=O)(OCH3)2 15.2 Cl Cl -CH2--CH2-P(=0)(0CH3)2 X~X.3 Cl F --CHz--CH2-P(=O)(OCH3)2 X~4 Cl H --CH2-cH2--P(=o)(oc2H5)2 X~IX.5 Cl Cl --CH2-CH2--P(=O)(OC2Hs)2 20XXXIX.6 Cl F --CH2--CH2--P(=o)(oc2Hs)2 X~IX.7 Cl H -CH2-CH(Cl)--P(=O)(OC~3)2X~X.8 Cl Cl -CH2-CH(Cl)--P(=O)(0CH3)2X~X.9 Cl F -CH2--CH(Cl)-P(=O)(0CH3)225XXXIX.10 Cl H -CH2-CH(Cl)--P(=o)(oc2Hs)2 X~X.ll Cl Cl -CH2-CH(Cl)-P(=0)(0C2Hs)2X~IX.12 Cl F -cH2-cH(cl)-p(=o)(oc2H5)2X~X.13 Cl H -CH2-CH(13r)-P(=O)(OCE~3)2 30X~X.14 Cl Cl -CH2-CH(Br)-P(=O)(OC~3)2 X~IX.15 Cl F -CH2-CH(Br)-P(=O)(OCH3)2 X~X.16 Cl H -CH2-CH(Br)--P(=O)(Oc2Hs)2 X~WX.17 Cl Cl -cH2-cH(Br)-p(=o)(oc2H5)235X~x.18 Cl F -cH2-cH(Br)-p(=o)(oc2Hs)2X~IX.l9 Cl H -CH2-CH(C~)--P(=O)(0CE~3)2 X~X.20 Cl Cl -CH2-CH(CN)-P(=O)(OC~)2 X~.21 Cl F -CH2-CH(CN)-P(=O)(OCH3)2 40X~X.22 Cl H -cH2-cH(cN)-p(=o)(oc2Hs)2 X~X.23 Cl Cl -CH2-CH(CN)--P(=O)(OC2Hs)2 ~X.24 Cl F --CH2--CH(CN)--P(=O)(OC2Hs)2 ~X.25 Cl H -CH=CH--P(=O)(OCH3)2 45X~X.26 Cl Cl -CH=CH--P(=O)(OCH3)2 ~WX.27 Cl F -CH=CH--P(=O)(OCH3)2 - , 0050~46586 CA02245659 1998-08-06 No. R3 R4 --Eth--P(=Yl)(Y2Rl)~y3R2) X~X.28 Cl H --CH=CH-P(=O)(OC2Hs)2 X~.29 Cl Cl -CH=CH-P(=O)(Oc2Hs)2 5X~IX.30 Cl F --CH=CH-P(=O)(OC2H5)2 X~X.3 1 Cl H --CH=C(CI)--P(=O)(OC~3)2 X~X.32 Cl Cl --CH=C(Cl)-P(=O)(OCEO2 - X~lX.33 Cl F --CH=C(Cl)-P(=O)(OCH3)2 10X~IX.34 Cl H -CH=C(CI)-P(=O)(OC2Hs)2 ~X.35 Cl Cl --CH=C(Cl)-P(=O)(OC2Hs)2 X~X.36 Cl F --CH=C(Cl)-P(=O)(OC2Hs)2 X~X.37 Cl H -CH=C(Br)-P(=O)(OCH3)2 15X~IX.38 Cl Cl -cH=c(Br)-p(=o)(oc~)2 X~IX.39 Cl F -CH=C(Br)-P(=O)(OC~)2 f X~X.40 Cl H -cH=c(Br)-p(=o)(oc2Hs)2 X~.41 Cl Cl -CH=C(13r)-P(=O)(OC2Hs)2 zo~X.42 Cl F -CH=C(Br)-P(=O)(OC2Hs)2 X~X.43 Cl H -CH=C(CN)-P(=O)(OCE~)2 X~.44 Cl Cl -CH=C(CN)--P(=O)(OCH3)2 X~IX.45 Cl F -CH=C(CN)-P(=O)(OCH3)2 25.46 Cl H --CH=C(CN)--P(=o)(oc2Hs)2 X~X.47 Cl Cl -CH=C~CN)--P(=O)(OC2Hs)2 X~.48 Cl F -CH=C(CN)--P(=o)(oc2Hs)2 30 C.3.2)Preparation of the isothiocyanates XL by reacting ~nil;nes of the form~ XXXI with thiophosgene in the presence of a base:
.' H2N yl csc12 + R4 ~ Eth p Y2Rl ~ XL
XXXI
Examples of suitable diluents/solvents are hydrocarbons such as toluene and n-hex~ne, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran, or aprotic solvents such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
- ~ 0050/46586 CA 0224~6~9 1998-08-06 Suitable bases are mainly the alkali metal acetates, ~lk~l;
metal hydrogen carbonates, A 1 k~l; metal carbonates, alkali metal hydro~;~s or tertiary amines such as triethyl~; n~
and pyridine.
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
Especially preferred isothiocyanates of the fo 1 A XL are listed in Table 8 below.
Table 8S
. C
N yl R4 ~ Eth p y2Rl XL
y3R2 No. R3 R4 -E~-P(=Y1)CY2R1)~3R2) 2S ~.1 Cl H -cH2-cH2-p(=o)(ocH3)z .2 Cl Cl -CH2-CH2-P(=0)(0cH3)2 .3 Cl F -cH2-cH2-p(=o)(ocH3)2 .4 Cl H -cH2-cH2-p(=o)(oc2Hs)2 ~-5 Cl Cl -CH2-CH2-P(=O)(0c2Hs)2 .6 Cl F -CH2-CH2-P(=0)(0C2Hs)2 ~DL.7 Cl H -CH2-CH(Cl)-P(=0)(0CH3)2 ~.8 Cl Cl -CH2-CH(Cl)-P(=0)(0CH3)2 35 ~.9 . Cl F -cH2-cH(cl)-p(=o)(ocH3)2 .10 Cl H -cH2-cH(cl)-p(=o)(oc2Hs)2 .11 Cl Cl -CH2-CH(Cl)-P~=O)(OC2Hs)2 ~.12 Cl F -cH2-cH(cl)-p(=o)(oc2Hs)2 40~.13 Cl H -CH2-CH ~r)-P(=O)(OCH3)2 .14 Cl Cl -cH2-cH~Br)-p(=o)(ocH3)2 .15 Cl F -CH2-CH~Br)-P(=O)(OCH3)2 ~.16 Cl H -CH2-CH~Br)-P(=O)~OC2Hs)2 4S~.17 Cl Cl -CH2-CH ~r)-p(=o)(oc2Hs)2 ~.18 Cl F -CH2-CH~r)-P(=0)(OC2Hs)2 - '0050/46586 CA 02245659 1998-08-06 .
No. R3 R4 -Eth-P(=Yl)CY2Rl)CY3R2) L.l9 Cl H -CH2-CH(CN~-P(=O)(OC~3)2 ~DL.20 Cl Cl --CH2-CH(CN~--P(=O)(OCH3)2 5 ~DL.21 Cl F -CH2--CH(CN~-P(=O)(OCH3)Z
L.22 Cl H -cH2-cH(cN~-p(=o)(oc2Hs)2 ~DL.23 Cl Cl -CH2-CH(CN~-P(=O)(OC2Hs)2 ~nL.24 Cl F --CH2-CH(CN~-P(=O)(OC2Hs)2 10 ~nL.25 Cl H --CH=CH--P(=O)(OCH3)2 ~DL.26 Cl Cl -CH=CH-P(=O)(OcH3)z L.27 Cl F -CH=CH-P(=O)(OcH3)2 ~L.28 Cl H -CH=CH-P(=O)(Oc2H5)2 15 ~3L.29 Cl Cl -CH=CH-P(=O)(OC2Hs)2 ~nL.30 Cl F -CH=CH-P(=O)(Oc2Hs)2 f ~DL.31 Cl H --CH=C(Cl)--P(=O)(OCH3)2 ~nL.32 Cl Cl -CH=C(Cl)-P(=O)(OCH3)2 20 ~DL.33 Cl F -CH=C(Cl)-P(=O)(OCH3)2 ~L.34 Cl H --CH=C(Cl)-P(=O)(OC2Hs)2 ~L.35 Cl Cl --CH=C(Cl)-P(=O)(Oc2Hs~
~DL.36 Cl F --CH=C(Cl)--P(=o)(oc2Hs)2 25 ~nL.37 Cl H -CH=C~Br)-P(=O)(OCHO2 L.38 Cl Cl -cH=c~Br)-p(=o)(oc~3)2 L.39 Cl F -cH=c~Br)-p(=o)(oc~3)2 ~L.40 Cl H -cH=c~Br)-p(=o)(oc2Hs)2 ~L.41 Cl Cl -cH=c~Br)-p(=o)(oc2Hs)2 ~DL.42 Cl F -CH=C~Br)-P(=O)(OC2Hs)2 - ~DL.43 Cl H -CH=C(CN~-P(=O)(OCH3)2~- ~DL.44 Cl Cl -CH=C(CN~-P(=O)(OCH~)2~DL 45 Cl F - CH=C(C~9-P(=O)(OCH3)2 ~DL 46 Cl H --CH=C(CN~--P(=o)(oc2Hs)2 .47 Cl Cl -CH=C(CN~-P(=O)(Oc2Hs)2 ~L.48 Cl F -CH=C(CN9-P(=O)(OC2Hs)2 ~ 0050/46586 CA 0224~659 1998-08-06 ~ - 146 ~
C.4) Synthesis of the pyrrolothiadiazole ring 5Rss NH(-HX) R55 NH2( HX) N +XL
,,NH or ~ ~
~ R56 i --~
HN yl R4 ~ Eth- 1I y2Rl oxidation 5 XLIV
X is the anion of the acid, preferably a chloride, bromide, hydrogen sulfate or 1/2 sulfate ion.
In this process, an isothiocyanate of the formula XL is reacted with an ~m; ~; ne of the fo 1~ XLII or XLIII.
he process is nor~-l ly carried out in an inert solvent/
diluent, e.g. in a h~dLocarbon such as toluene and n-he~ne, a halogenated hydrocarbon such as dichlol~...eLhane, an ether such as tetrahydrofuran, an alcohol such as ethanol, or in an aprotic solvent such as dimethylformamide, acetonitrile and dimethyl sulfoxide.
Alternatively, XL can also be reacted with an acid addition salt of the Am; ~; ne XLII or XLIII ( for example with hydrochloric or sulfuric acid). In this case, the process is carried out in the presence of a base, for example an ~lk~l; metal acetate, ~1k~1 i metal hydrogen carbonate, 4S A 1 k~li metal carbonate, alkali metal hydroxide or a tertiary amine such as triethylamine or pyridine.
. ~ 0050/46586 CA 022456~9 1998-08-06 .
The reaction products of the formula XLIV are then oxidized in one of the solvents mentioned for the preparation of XLIV, preferably using a halogen such as chlorine or bromine.
Both the conversion of XL into XLIV and the oxidation of XLIV are generally carried out between the melting point and the boiling point of the reaction mixture in question, preferably at from 0 to 150~C.
C.5) Synthesis of the uracil ring by reacting an isocyanate of the forml~l A XLV with an aminoacrylic acid derivative oi~ the for~l~ XLVI in the presence of a strong base:
O
C
~ o_ ( Cl-C4-alkyl ~ + R4~ Eth--E~ y2Rl ~ base XLVI XLV
I ~R5 = ~1 ~
Examples of suitable solvents/diluents are hydrocarbons such as toluene and n-heYAne~ halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran or aprotic solvents such as dimethylfor--m;~e, acetonitrile . and dimethyl sulfoxide.
-Suitable bases are mainly the alkali metal hydrides, ~1 kA 1 i metal alkoxides, A lk~l; metal amides, alkali metal hydroY~es or alkyllithium cG...~o~nds such as butyllithium.
The reaction is generaliy carried out bet-wêen the mêltirlg point and the boiling point of the reaction mixture, preferably at from 0 to 150~C.
Those process products I where R5 is ~1 and R8 is hydrogen can subsequently be alkylated or aminated in the presence of a base:
. 45 - ~ 0050/46586 CA 0224~6~9 l998-08-06 I ~ R5 ~ ~1; R8 = EI~ + Cl--C4--alkyl--La I ~ R5 ~>
baseR3 = C1-C4-alkyl ~ Cl-C4-haloalkyl-La R5 = ~l I ~ R5 = ~1; R8 _ ~ ~ I' R8 = Cl-C4_ , base haloalkyl J
I ~ R5 = ~1 ; R8 = H } ; ~ R5 = ~1 ; R8 = NH2}
La is a customary leaving group, in particular h~l;~, triflate, tosylate or mesylate;
Lb is a customary leaving group, in particular ~
hydrogen sulfate, mono- or dinitroph~oxy, i.e., for example, chloro ine~ hydroxylr ;ne-O-sulfuric acid or 2,4-dinitrophenoxyamine.
The solvents mentioned for the synthesis of the uracil ring are likewise suitable here.
Examples of useful bases are the ~lk~l; metal acetates, ~l kA 1; metal hydrogen carbonates, alkali metal carbonates and ~1 k~ 1; metal hydroxides, and tertiary ~;nes such as triethylamine and pyridine.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from O to 150~C.
C.5.1)Preparation of the isocyanates XLV by reacting ~nil;nes of the formula XXXI with phosgene, diphosgene or triphosgene in the presence of a base:
E~2N yl COCl2 ~ 1I base ClCOOCCl3 ~ + R4 ~ Eth -- p Y2R1 3 XLV
~ (C13CO)2CO y3R2 XXXI
Examples of suitable solvents~diluents are hydrocarbons such as toluene and n-hexane, halogenated hydrocarbons such as dichloromethane, ethers such as tetrahydrofuran and ~ 0050/46586 CA 0224S6~9 1998-08-06 ~ .
aprotic solvents such as dim~ethylform~m;~e, acetonitrile and dimethyl sulfoxide.
Suitable bases are mainly the A 1 kA 1; metal acetates, alkali metal hydrogen carbonates, A l kA l; metal carbonates, alkali metal hydro~;~es or tertiary Am;nes such as triethyl Am; ne and pyridine.
The reaction is generally carried out between the melting point and the boiling point of the reaction mixture, preferably at from O to lSO~C.
C.6) Synthesis of a cyclic imide ring by reacting an ~n;line of the formula XXXI with an anhydride of the formula XLVII or XLVIII in the presence of an acid:
R13 o acid / ; I ~ R5 = ~3; y4 = o R14 ~,~~ H2N ' yl 20 o + R4 ~ Eth p--R21 o XXXI
\Z~
2Z - Z2 o ~ I R5 = ~6 ; y5,y6 = o;
acid ~, Zl and/or Il ~ Z2 = CH
XLVIII
Examples of suitable acids are mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, carboxylic acids such as acetic acid or sulfonic acids such as benzene- and toluenesulfonic acid.
The process is no -l~y carried out in an inel~ solvel..~
diluent, for example in a hydrocarbon such as toluene or n-h~YAne, a halogenated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran, an alcohol such as ethanol, a carboxylic acid such as acetic acid, or in an aprotic solvent such as dimethylform~m;~e, acetonitrile or dimethyl sulfoxide.
- 0050/46586 CA 0224~6~9 1998-08-06 .
150 -~
The reaction is carried out between the melting point and the boiling point of the reaction mixture, preferably at from 0 to 150~.
5 Unless otherwise specified, all processes described above are ex-pediently carried out under atmospheric pressure or under the in-herent autogeneous pressure of the reaction mixture in question.
In general, the reactants are employed in a molar ratio of from 0.95:1 to 5:1.
As a rule, the reaction mixtures are worked up by methods known per se, for example by diluting the reaction solution with water followed by isolation of the product by means of filtration, 15 crystallization or solvent extraction, or by 1 ~ving the solvent, partitioning the residue in a mixture of ~ water and a suitable organic solvent and working up the organic f phase to give the product.
20 The substituted aromatic phosphonic acid derivatives I can be ob-t~;ne~ from their preparation as isomer mixtures which, however, can be separated into the pure isomers, if desired, by the methods customary for this purpose, such as crystallization or chromatography, also on an opt;cA~ly active adsorbate. Pure op-25 tically active isomers can be prepared advantageously from suit-able optically active starting materials.
Agriculturally useful salts of the cG...~ounds I can be formed by reaction with a base of the cation in question, preferably an al-30 kali metal hydroxide or alkali metal hydride, or by reaction withan acid of the anion in question, preferably of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or nitric - acid.
Salts of I whose metal ion is not an alkali metal ion can also be prepared in the customary m~nne~ by double decomposition of the alkali metal salt in question, and ammonium, phosphonium, sulfo-nium and sulfoxonium salts using ammonia, phosphonium hydroxide, 40 sulfonium hydroxide or sulfoxonium hydroxide.
The compounds I and their agriculturally useful salts, both as isomer mixtures and in the form of the pure isomers, are suitable as herbicides. The herbicidal compositions comprising I are ca-45 pable of effecting very good vegetation control on non-crop areas, especially at high rates of application. In crops such as wheat, rice, maize, soybeans and cotton, they are active against ~ 0050/46586 CA 0224~6~9 1998-08-06 .
broad-leaved weeds and grass weeds without damaging the crop plants to a substantial extent. This effect is observed especial-ly at low rates of application.
5 Depending on the application method in ~uestion, the compounds I, or the herbicidal compositions comprising them, can also be employed in a further nl~mb~ of crop plants for el ;m; n~ting unde-sirable plants. Suitable crops are for example the following:
10 Allium cepa, AnAn~ comosus, Arachis hypogaea, Asparagus offici-- nalis, Beta vulgaris spec. altissima, Beta vulgaris spec. rapa, - srassica napus var. napus, Brassica napus var. nApobrassica~
srassica rapa var. silvestris, Camellia sinensis, Carth~mlla tinc-torius, Carya ill;noinensis, Citrus limon, Citrus sinensis, Cof-15 fea arabica (Coffea canephora, Coffea liberica), Cucumis satiw s,Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgare, Humulus lupulus, Ipomoea ba-20 tatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycop-ersicon lycopersicum, Malus spec., M~n;hot esculenta, Medicago sativa, Musa spec., Nicotiana tabacum (N. rustica), Olea euro-paea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus spec., Pisum sativum, Prunus avium, Prunus persica, 25 Pyrus cn~ n; ~, ~ibes sylvestre, Ricinus c~ ni~ Saccharum officinarum, Secale cereale, Solanum tuberosum, Sorghum bicolor (S. w lgare), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera and Zea mays.
In addition, the compounds I can also be used in crops which tol-erate the action of herbicides as a result of breeding, including genetic engineering methods.
35 Moreover, the substituted aromatic phosphonic acid derivatives I
are also suitable for desiccating and/or defoliating plants.
As desiccants, they are especially suitable for desiccating the aerial parts of crop plants such as potatoes, oilseed rape, sun-40 flowers and soybeans. This allows completely mechanical harvest-ing of these important crop plants.
Also of economic interest is to facilitate harvesting, which is 45 made possible by concentrating, over a period of time, dehis-cence, or reducing the adherence to the tree, in citrus fruit, olives or other species of pomaceous fruit, stone fruit and nuts.
The same mech~n; fi~, i.e. promotion of the formation of abscission 0050/46586 CA 0224~6~9 l998-08-06 tissue between fruit or leaf and shoot of the plants, is also im-portant for readily controllable defoliation of useful plants, in particular cotton.
5 ~oreover, shortening the period within which the individual cot-ton plants mature results in an improved fiber quality after harvesting.
10 The compounds I or the compositions comprising them can be used for example in the form of directly sprayable aqueous solutions, powders, suspensions, also highly concentrated aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, materials for spreading or granules, by means or 1~ spraying, atomizing, dusting, spreading or pouring. The use forms depend on the int~n~e~ aims; in any case, they should guarantee the finest possible distribution of the active ingredients ac-f~ cording to the invention.
zo Suitable inert a~ ries are mainly: mineral oil fractions ofmedium to high boiling point, such as kerosene and diesel oil, furthermore coal tar oils and oils of vegetable or ~nim~l origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. paraffins, te-trahydronaphthalene, alkylated naphthalenes and their deriva-25 tives, alkylated benzenes and their derivatives, alcohols such asmethanol, ethanol, propanol, butanol and cycloh~x~nol, ketones such as cycloh~none, strongly polar solvents, e.g. amines, such as N-methylpyrrolidone, and water.
30 Aqueous use forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible gran-ules by adding water. To prepare emulsions, pastes or oil disper-sions, the substrates, as such or dissolved in an oil or solvent, can be homogenized in water by means of a wetting agent, tack-35 ifier, dispersant or emulsifier. Alternatively, it is possible toprepare concentrates comprising active substance, wetting agent, t~ck;fier, dispersant or emulsifier and, if desired, solvent or oil, which are suitable for dilution with water.
40 Suitable surfactants are the alkali metal salts, alkaline earth metal salts and ammonium salts of aromatic sulfonic acids, e.g.
ligno-, phenol-, naphthalene- and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- and alkylarylsulfonates, of alkyl sulfates, lauryl ethyl sulfates and fatty alcohol sulfates, 45 and the salts of sulfated hexa-, hepta- and octadecanols and of fatty alcohol glycol ethers; condensates of sulfonated naphtha-lene and its derivatives with formaldehyde, condensates of naph-0050/46586 CA 0224~6~9 1998-08-06 .
153 _ thalene or o~ the naphthalenesulfonic acids with phenol and for-maldehyde, polyoxyethylene octylp~enol ether, ethoxylated isooc-tyl-, octyl- or nonylphenol~ alkylphenyl polyglycol ether, tribu-tylphenyl polyglycol ether, alkylaryl polyether alcohols, iso-5 tridecyl alcohol, fatty alcohol/ethyleneoxide condensates,ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxy-propylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin-sulfite waste liquors or methylcellulose.
10 Powders, materials for spreading and dusts can be prepared by mixing or grinding together the active substances with a solid carrier .
15 Granules, e.g. coated granules, impregnated granules and homo-geneous granules, can be prepared by binding the active ingredi-ents to solid carriers. Solid carriers are mineral earths, such as silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loss, clay, dolomite, diatomaceous earth, cal-20 cium sulfate, magnesium sulfate, magnesium oxide, ground syn-thetic materials, fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, and products of vegetable origin, such as cereal meal, tree bark meal, wood meal and nut-shell meal, cellulose powders or other solid carriers.
The concentrations of the active ingredients I in the ready-to-use prQducts can be varied within wide ranges. In general, the formulations comprise approximately from 0.001 to 98 % by weight, preferably 0.01 to 95 % by weight, of at least one active in-30 gredient. The active ingredients are employed in a purity of from 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
,, _, ~_ The formulation examples which follow illustrate the preparation of such products:
I. 20 parts by weight of the compound No. IAh.432 are dis-solved in a mixture composed of 80 parts by weight of alky-lated benzene, 10 parts by weight of the adduct of 8 to 10 mol of ethylene oxide to 1 mol of oleic acid N-monoethano-lAmi~e, 5 parts by weight of calcium dodecylbenzenesulfo-nate and 5 parts by weight of the adduct of 40 mol of eth-ylene oxide to 1 mol of castor oil. Pouring the solution into 100,000 parts by weight of water and finely distribut-ing it therein gives an aqueous dispersion which comprises 0.02 % by weight of the active ingredient.
.
. ~ OOSO/46586 CA 022456~9 1998-08-06 .
II. 20 parts by weight of the compound No. IAh.861 are dis-solved in a mixture comrosed of 40 parts by weight of cy-cloheYAnnne, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 7 mol of ethylene oxide to 1 mol of S isooctylphenol and 10 parts by weight of the adduct of 40 mol of ethylene oxide to 1 mol of castor oil. Pouring the solution into 100,000 parts by weight of water and finely distributing it therein gives an aqueous dispersion which comprises 0.02 % by weight of the active ingredient.
III. 20 parts by weight of the active ingredient No. IBg.861 are dissolved in a mixture composed of 25 parts by weight of cyclohe~none, 65 parts by weight of a mineral oil fraction of boiling point 210 to 280~C and 10 parts by weight of the adduct of 40 mol of ethylene oxide to 1 mol of castor oil.
Pouring the solution into 100,000 parts by weight of water and finely distributing it therein gives an aqueous disper-sion which comprises 0.02 % by weight of the active ingre-dient.
IV. 20 parts by weight of the active ingredient No. ICh.860 are mixed thoroughly with 3 parts by weight of sodium diisobu-tylnaphthalene-~-sulfonate, 17 parts by weight of the so-dium salt of a lignosulfonic acid from a sulfite waste liq-uor and 60 parts by weight of pulverulent silica gel and the mixture is ground in a hA~?r mill. Finely distributing the mixture in 20,000 parts by weight of water gives a spray mixture which comprises 0.1 % by weight of the active ingredient~
V. 3 parts by weight of the active ingredient No. ICh.llS4 are mixed with 97 parts by weight of finely divided kaolin.
This gives a dust which comprises 3 ~ by weight of the active ingredient.
VI. 20 parts by weight of the active ingredient No. Ish.860 are mixed intimately with 2 parts by weight of calcium dodecylbenzenesulfonate, 8 parts by weight of fatty alcohol polyglycol ether, 2 parts by weight of sodium salt of a phenol/urea/formaldehyde condensate and 68 parts by weight of a paraffinic mineral oil. This gives a stable oily dis-persion.
45 VII. 1 part by weight of the compound No. IBh.861 is dissolved in a mixture composed of 70 parts by weight of cyclohexa-none, 20 parts by weight of ethoxylated isooctylphenol and CA 0224~6~9 l998-08-06 .
155 _ 10 parts by weight of ethoxylated castor oil. The resulting mixture can then be diluted with water to the desired con-centration of active ingredient. This gives a stable emul-sion concentrate.
s VIII. 1 part by weight of the c~ und No. IBh.1154 is dissolved in a mixture composed of 80 parts by weight of cyclohexa-none and 20 parts by weight of Wettol~ E~ 31 (= nonionic emulsifier based on ethoxylated castor oil; BASF AG). The resulting mixture can then be diluted with water to the desired concentration of active ingredient. This gives a stable emulsion concentrate.
15 The active ingredients I or the herbicidal compositions can be applied pre- or post-emergence. If the active ingredients are less well tolerated by certain crop plants, application tech-niques may be used in which the herbicidal compositions are sprayed, with the aid of the spraying apparatus, in such a way 20 that they come into as little contact, if any, with the leaves of the sensitive crop plants, while the active ingredients reach the leaves of undesirable plants which grow underneath, or the bare soil sur~ace (post-directed~ lay-by).
25 Depending on the aim of control, the season, the target plants and the growth stage, the application rates of active ingredient I are from 0.001 to 3.0, preferably 0.01 to 1.0, kg of active substance (a.s.) per ha.
30 To widen the spectrum of action and to achieve synergistic ef-fects, the substituted aromatic phosphonic acid derivatives I may be mixed with a large number of representatives of other herbici-dal or growth-regulating active ingredients and applied jointly.
Suitable examples of components in mixtures are 1,2,4-th;A~
zoles, 1,3,4- th; AA;~zoles, amides, aminophosphoric acid and its derivatives, aminotriazoles, ~n; 1; ~es, aryloxy-/hetaryloxyalka-noic acids and their derivatives, benzoic acid and its deriva-40 tives, benzoth;~A;A~inones, 2-(hetaroyl/aroyl)-1,3-cyclohexane-diones, hetaryl-aryl-ketones, benzylisoxazolidinones, meta-CF3-phenyl derivatives, carbamates, quinol;necA~boxylic acid and its derivatives, chloroacet~n;l;des, cycloh~YAne-1,3-dione de-rivatives, diazines, dichloropropionic acid and its derivatives, 45 dihydrobenzofurans, dihydrofuran-3-ones, dinitroanilines, dini-trophenols, diphenyl ethers, dipyridyls, halocarboxylic acids and their derivatives, ureas, 3-phenyluracils, imidazoles, imidazoli-nones, N-phenyl-3,4,5,6-tetrahydrophthAl;~; AeS, o~AA;Azoles, oxi-CA 022456~9 1998-08-06 .
~anes, phenols, aryloxy- and hetaryloxyphenoxypropionic esters, phenylacetic acid and its derivatives, 2-phenylpropionic acid and its derivatives, pyrazoles, phenylpyrazoles, pyridazines, pyri-dinecarboxylic acid and its derivatives, pyrimidyl ethers, sulfo-5 n~ es, sulfonylureas, triazines, triazinones, triazolinones,triazolcarbo~A~;~s and uracils.
It may furthe~more be advantageous to apply the compounds I, alone or in com~ination with other herbicides, together with 10 further crop protection agents, for example with pesticides or with agents for controlling phytopathogenic fungi or bacteria.
Also of interest is the miscibility with mineral salt solutions, which are employed for treating nutritional and trace element deficiencies. ~on-phytotoxic oils and oil concentrates may also 15 be added~
Preparation examples 20 EXample 1 Diethyl 2-(2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-py-razol-3-yl)-4-fluorophenyl)vinylphosphonate (No. IBg.861) 1 g (3 mmol) of tetraethyl methanediphosphonate was dissolved in 25 50 ml of toluene and treated with 80 mg (3.2 mmol) of sodium hy-dride. After the evolution of gas had ceased, a solution of 1 g (2.9 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoroh~nz~ldehyde in 50 ml of toluene was added.
The reaction mixture was subsequently stirred for 16 hours at 30 room temperature and then treated with 0.15 1 of water. The prod-uct of value was extracted from the aqueous phase usiny 50 ml of toluene. Finally, the combined organic phases, in turn, were washed with water and then dried over magnesium sulfate and con-centrated. Yield: 1.1 g.
Precursor 1.1 5-(4-Chloro-2-fluoro-5-methylphenyl)-1,2-dihydro-2-methyl-3H-pyrazol-3-one 34.7 g (0.75 mol) of methylhydrazine were added to a solution of 177 g (0.68 mol) of ethyl 3-(4-chloro-2-fluoro-5-methylphe-nyl)-3-o~opl~pionate in 500 ml of diethylene glycol. After 6 hours at 100~C, the mixture was poured into 4 1 of water. The so-45 lids were subsequently removed and dried. Yield: 133 g; m.p.:155-156~C.
0050/46586 CA 0224~6~9 1998-08-06 Precursor 1.2 3-(4-Chloro-2-fluoro-5-methylphenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole Gaseous chlorodifluoromethane was passed for 2 hours into a sol-ution of 133 g (0.55 mol) of 5-(4-chloro-2-fluoro-5-methylphe-nyl)-1,2-dihydro-2-methyl-3H-pyrazol-3-one and 110 g (2.7 mol~ of sodium hydroxide in 1 1 of ~;ox~ne and 0.5 1 of water at room temperature. The reaction solution was then poured into 2 1 of-water, whereupon the aqueous phase was extracted three times using ethyl acetate. The combined organic phases were dried over magnesium sulfate and then filtered and concentrated. The residue was purified by means of column chromatography on silica gel 15 (eluent: cyclohex~ne/ethyl acetate = 9:1) followed by preparative MPLC on silica gel (identical eluent). Yield: 43 g.
NMR (250 MHz; in CDCl3): ~ tppm] = 2.37 (s,3H), 3.80 (s,3H), - 6.30 (s,lH), 6.57 (t,lH), 7.14 (d,lH), 7.82 (d,lH).
20 PrecursOr 1.3 4-Chloro-3-(4-chloro-2-fluoro-5-methylphenyl)-5-difluorome-thoxy-l-methyl-lH-pyrazole 25 22 g (0.16 mol) of sulfuryl chloride were added dropwise to a solution of 43 g (0.lS mol) of 3-(4-chloro-2-fluoro-5-methylphe-nyl)-5-difluoromethoxy-1-methyl-lH-pyrazole in 250 ml of tetrach-loromethane. After the reaction solution had subsequently been stirred for 16 hours, 200 ml of saturated aqueous sodium hydloyen 30 carbonate solution was added dropwise. The organic phase was then separated off, washed using saturated sodium chloride solution, dried over magnesium sulfate, then filtered and finally concen-trated. Yield: 46 g.
lH NMR (250 MHz; in CDCl3): ~ [ppm] = 2.37 (s,3H), 3.84 (s,3H), 35 6.71 (t,lH), 7.21 (d,lH), 7.40 (d,lH).
Precursor 1.4 4-Chloro-3-(4-chloro-5-diLLI ~thyl-2-fluorophenyl)-5-difluo-romethoxy-1-methyl-lH-pyrazole A solution of 46 g (0.14 mol) of 4-chloro-3-(4-chloro-2-fluoro-5-methylphenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole and 62.9 g (0.35 mol) of N-bromosuccin;mi~e in 2 1 of tetrachloromethane was 45 irradiated for 3.5 hours with a 1500 watt high-pressure mercury OOS0/46586 CA 0224~6~9 1998-08-06 .
lamp and a W lamp. The solids content was subsequently filtered off and washed two more times using tetrachloromethane. The com-bined filtrates were then concentrated. Yield: 68 g.
lH NMR (270 MHz; in CDCl3): a tppm] = 3.86 (s,3H), 6.72 (t,lH), 5 7.05 (s,lH), 7.19 (d,lH), 8.23 (d,lH).
Precursor 1.5 2-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyra-lO zol-3-yl)-4-fluorobenzaldehyde 68 g (0.14 mol) of 4-chloro-3-(4-chloro-5-dibLom~llethyl-2-fluoro-phenyl)-5-difluoromethoxy-1-methyl-lH-pyrazole were dissolved in 200 ml of concentrated sulfuric acid, with ice-cooling, whereupon 15 the mixture was heated at 100~C until the evolution of gas had ceased. It was then poured into 4 1 of ice-water. The mixture was f-- subsequently extracted three times using ethyl acetate. The com-bined organic phases were washed with water, then dried over mag-nesium sulfate and finally concentrated. The crude product was 20 purified by means of silica gel column chromatography (eluent:
h~Ane/ethyl acetate = 8:1). Yield: 35 g; m.p.: 95-98 ~C.
Example 2 Diethyl l-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No.
IBh.861) 2 ml of a butyllithium solution (1.6 M in he~ne; 3.Z mmol) were 30 added in such a way to a solution, cooled at (-70)~C, of 1.63 g (6.4 mmol) of diethyl trichloromethanephosphonate in 20 ml of te-trahydrofuran that the temperature did not exceed (-65)~C. Stir-ring was subsequently continued for 1 hour at from (-65) to (-70)~C, whereupon a solution of 1 g (2.9 mmol) of 2-chlo-35 ro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorobenzaldehyde in 20 ml of tetrahydrofuran was slowly added dropwise. Stirring was continued for 30 minutes, the cooling bath was then le -~ed, and stirring was continued for a further 16 hours, during which process the temperature of the mixture 40 climbed to approximately 20~C. After 5 g of ammonium chloride had been added, the reaction mixture was poured into 50 ml of water.
The product of value was then obt~; neA from the aqueous phase by extracting it twice using in each case 50 ml of methyl tert-butyl ether. The combined organic phases were washed using saturated 45 aqueous sodium chloride solution and water, dried over magnesium sulfate and finally concentrated. The crude product was purified - , 0050/46586 CA 0224~6~9 1998-08-06 .
by means of silica gel column chromatography (eluent: he~Ane!
ethyl acetate = 4:1). Yield: 0.7 g.
Example 3 Diethyl 2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-(lH,3H)-pyr;miA;ne~;on-3-yl)phenyl]vinylphosphonate (No. IAg.861) 0.12 g (4.7 mmol) of sodium hydride was added to a solution of 10 1.5 g (5.2 mmol) of tetraethyl methanediphosphonate in 50 ml of toluene. After the evolution of gas had ceased, a solution of 1.5 g (4.3 mmol) of 2-chloro-4-fluoro-S-(l-methyl-6-trifluorome-thyl-2,4(1H,3H)-pyr;m;~;ne~;on-3-yl)benzaldehyde in 50 ml of to-luene was added. The mixture was subsequently stirred for a 15 further 16 hours at approximately 20~C. For working-up, the reac-tion mixture was treated with 0.15 1 of water. Residues of the ~- product of value which had r~m~; ne~ in the aqueous phase were ex-tracted using 50 ml of toluene. The combined organic phases were subsequently washed with water, dried over magnesium sulfate and 20 finally concentrated. Yield: 1.4 g.
Precursor 3.1 2-Chloro-4-fluoro-5-isocyanatohen7aldehyde (O-methyl)oxime 411.3 g of diphosgene (2.08 mol) were added dropwise to a sol-ution of 383 g (1.89 mol) of 5-amino-2-chloro-4-fluorobenz-aldehyde (O-methyl)oxime in 2 1 of toluene. The temperature was then slowly raised to 110 ~C in the course of approximately 30 6 hours so that the evolution of gas proceeded in a controlled ~nn~r, The mixture was subsequently refluxed for a further 5 hours. The reaction mixture was then left to cool and finally concentrated. Yield: 432 g.
The product was processed without purification.
Precursor 3.2 2-Chloro-4-fluoro-5-(6-trifluoromethyl-2,4(1H,3H)-pyr; ;~;ne-dion-3-yl)benzaldehyde (O-methyl)oxime A solution of 168.5 g (0.92 mol) of ethyl 3-amino-4,4,4-trifluo-rocrotonate in 0.1 1 of dimethylformAm;~e was added dropwise with ice-cooling to 30.4 g (1.01 mol) of 80 % by weight sodium hydride in 0.5 1 of dimethylform-m; Ae . After one hour at this tempera-45 ture, the mixture was cooled to (-30) to (-35)~C, and a solution of 210.3 g (0.92 mol) of 2-chloro-4-fluoro-5-isocyanatobenz-aldehyde (O-methyl)oxime in 0.15 1 of tetrahydrofuran was added dropwise. The reaction mixture was then stirred for 20 hours at ~ 0050/46586 CA 0224~6~9 l998-08-06 - - 160 ~
approximately 20~C, and 1.5 1 of water were subsequently added with ice-cooling. Undissolved matter in the mixture formed was removed and washed using 300 ml of water. The combined filtrates were acidified using dilute hydrochloric acid. The product of 5 value was then extracted from the solution obtained using dichlo-romethane. The extract was washed with water, dried over sodium sulfate and finally concentrated. Yield: 289 g; m.p.: 176-177~C
(diisG~lopyl ether/petroleum ether).
10 Precursor 3.3 2-Chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyri-midinedion-3-yl)benzaldehyde (O-methyl)oxime 15 First, 117.1 g (0.85 mol) of potassium carbonate were added to a solution of 281.6 g (0.77 mol) of 2-chloro-4-fluoro-5-(6-trifluo-romethyl-2,4(lH,3H)-pyrimidinedion-3-yl) hen 7~1 ~hyde (O-methyl)oxime in 0.8 1 of dimethylfor~ e, whereupon a solution of 120.2 g of methyl iodide (0.85 mol) in 0.1 l of dimethylforma-20 mide was added dropwise in the course of 1 hour. The reactionmixture was subsequently stirred for 20 hours at approximately 20~C, and 0.9 l of water was subsequently added dropwise with ice-cooling. The product of value was extracted from the resulting solution using 1 l of dichloromethane. The extract was washed 25 three times using 300 ml of water, dried over sodium sulfate and finally concentrated. Yield: 241 g; m.p.: 141-142~C (diisopropyl ether).
Precursor 3.4 30 2-Chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyri-mi~; ne~; on-3-yl)benzaldehyde 150 ml of a 30 % by weight aqueous formaldehyde solution and 150 35 ml of concentrated hydrochloric acid were added dropwise to a solution of 189.9 g (0.50 mol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimi~; ne~; on-3-yl)benzalde-hyde (O-methyl)oxime in 0.75 l of glacial acetic acid. The mix-ture was subsequently refluxed for two hours. After cooling, 0.75 40 l of water were added, whereupon the solid product of value formed was separated off and washed first with water until the reaction was neutral and then with petroleum ether. Yield: 140 g;
m.p.: 175-178~C.
. ~ 0050/46586 CA 0224~6~9 1998-08-06 .
Example 4 Diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluorome-thyl-2,4(1H,3H)-pyrimi~ine~;on-3-yl)phenyl~vinylphosphonate (No.
IAh.861) 3.2 ml of a butyllithium solution (1.5 M in hexane; 4.8 mmol) were added in such a way to a solution, cooled at (-70)~C, of 2.4 g (9.5 mmol) of diethyl trichloromethane phosphonate in 30 ml of 10 tetrahydrofuran that the temre~ature did not exceed (-65)~C. The mixture was then stirred for 1 hour at from (-65) to (-70)~C, whereupon a solution of 1.5 g (4.3 mmol) of 2-chloro-4-fluoro-5--(1--methyl-6--trifluoromethyl-2,4(1H,3H)--pyr;~;tl;ne~;on--3--yl)ben-zaldehyde in 20 ml of tetrahydrofuran was slowly added dropwise.
15 30 minutes later, the cooling bath was ~ ~-ved, and the mixture was allowed to come to room te~r~rature in the course of 16 hours. After 3.6 g of ammonium chloride had been added, the reac-tion mixture was poured into 20 ml of water. The product was ex-tracted twice from the aqueous phase using in each case 50 ml of 20 methyl tert-butyl ether. The combined organic phases were washed using saturated aqueous sodium chloride solution and water, dried over magnesium sulfate and finally concentrated. The crude prod-uct was purified by means of silica gel column chromatography (eluent: hexane/ethyl acetate - 4:1). Yield: 0.7 g.
Example 5 Dimethyl l-chloro-2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)ethylphosphonate (No. IEb.2) 30 2.8 g (10 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)~n;line were added to a solution of 31.2 g (0.23 mol) of dimethyl vinylphosphonate, 1.6 g (12 mmol) of copper(II) ~_ chloride and 1.6 g ~16 mmol) of tert-butyl nitrite in 200 ml of acetonitrile. After the reaction mixture had been stirred for 2 35 hours, 200 ml of methyl tert-butyl ether were added. The organic phase was subsequently washed twice using in each case 50 ml of water and then dried over magnesium sulfate and finally concen-trated. The crude product was purified by means of silica gel column chromatography (eluent: first cycloh~n~/methyl tert-gO butyl ether = 4:1, then ethyl acetate). Yield: 2.0 g.
.
CA 0224~6~9 1998-08-06 Example 6 Dimethyl l-chloro-2-(2-chloro-5-(5-chloro-1-difluoromethyl-2-methyl-lH-;~;~zol-4-yl)phenyl)ethylphosphonate (No. IHb.2) A solution of 42.5 g (0.26 mol) of dimethyl vinylphosphonate, 2.5 g of copper(II) chloride (19 mmol) and 1.7 g (17 mmol) of tert-butyl nitrite in 100 ml of acetonitrile was stirred for 30 min-ute~, and a solution of 3.8 g (13 mmol) of 2-chloro-5-(5-chloro-10 1-difluoromethyl-2-methyl-lH-imidazol-4-yl)~n;l;ne in 20 ml of acetonitrile was subsequently added. After 1 further hour, the mixture was concentrated, and the residue was then treated with 50 ml of water. The product was extracted from the aqueous phase using 50 ml of ethyl acetate. The organic phase was dried over 15 magnesium sulfate, filtered and finally concentrated. The crude product was purified by means of silica gel column chromatography (eluent: h~x~n~/ethyl acetate 2 4:1). Yield: 0.8 g.
Precursor 6.1 20 4(5)-(4-chlorophenyl)-2-methyl-lH-;m;~7ole 28.6 g (0.65 mol) of acetaldehyde were added dropwise with cool-ing to 320 ml of 25 % by weight aqueous ammonia solution. Then, 86.3 g (0.43 mol) of copper(II) acetate monohydrate and a sol-25 ution of 46 g (0.22 mol) of 1-(4-chlorophenyl)ethanon-2-yl acet-ate in 300 ml of dimethylform~m;de were added successively, whereupon the mixture was heated at 100~C for 30 minutes. The re-action mixture was subsequently poured into 3 1 of ice-water. The solids were filtered off and then taken up in 300 ml of ethanol.
30 Hydrogen sulfide gas was then pa~sed into this solution until sa-turation was reAche~, during which process black copper sulfide precipitated. After 5 g of active charcoal had been added, the mixture was stirred for a further 2 hours at reflux temperature, then cooled and filtered, and the filtrate was concentrated.
35 Yield: 31.5 g-1H NMR (270 MHz; in CDCl3): ~ tppm] = 2.41 (s,3H), 7.17 (s,2H),7.30 (d,2H), 7.61 (d,2H).
40 Precursor 6.2 4-(4-Chlorophenyl)-1-difluoromethyl-2-methyl-lH-imidazole 45.2 g (0.33 mol) of potassium carbonate were added to a solution of 31.5 g (0.16 mol) of 4(5)-(4-chlorophenyl)-2-methyl-lH-imida-45 zole in 150 ml of dimethylformamide. The mixture was then heatedat 90~C and chlorodifluoromethane gas was passed in for 2 hours.
The reaction mixture was subsequently poured into 300 ml of - 0050/46586 CA 022456~9 1998-08-06 .
water. The product was extracted three times from the aqueous phase using in each case 300 ml of ethyl acetate, whereupon the combined organic phases were washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate 5 and finally concentrated. Yield: 36 g.
lH NMR (270 MHz; in CDCl3): ~ lppml = 2.56 (s,3H), 7.04 (t,lH), 7.35 (m,3H), 7.68 (d,2H).
10 Precursor 6.3 5-Chloro-4-(4-chlorophenyl)-1-difluoromethyl-2-methyl-lH-Lmida-zole 26.7 g (0.19 mol) of sulfuryl chloride were added dropwise with 15 ice-cooling to a suspension of 24 g (98 mmol) of 4-(4-chlorophe-nyl)-l-difluoromethyl-2-methyl-lH-;m;~ole in 200 ml of tetrach-loromethane. After the reaction mixture had been stirred for 2 hours, an excess of saturated aqueous sodium hydrogen carbonate solution was added dropwise (still with ice-cooling). The solids 20 were subsequently filtered off. The organic phase was washed with water until neutral, dried over magnesium sulfate and concen-trated. The crude product was purified by means of silica gel column chromatography (eluent: hexA~e/ethyl acetate = 8:1).
Yield: 7.4 g.
25 lH NMR (270 MHz; in CDCl3): ~ tppm] ~ 2.60 (s,3H), 7.14 (t,lH), 7.38 (d,2H), 7.84 (d,2H).
Precursor 6.4 30 5-Chloro-4-(4-chloro-3-nitrophenyl)-1-difluoromethyl-2-methyl-lH-imidazole , . . .
8 g (28 mmol) of 5-chloro-4-(4-chlorophenyl)-1-difluoromethyl-2-methyl-lH-imidazole were cooled to (-40)~C, and 100 ml of concen-35 trated nitric acid were added. After 2 hours at (-20)~C, the mix-ture was poured into ice-water, whereupon the solid product of value was filtered off, washed with water and dried. Yield: 7 g.
lH NMR (270 MHz; in CDCl3): ~ [ppm] = 2.63 (s,3H), 7.16 (t,lH), 7.59 (d,lH), 8.09 (dd,lH), 8.47 (d,2H).
- ~ 0050/46586 CA 0224~6~9 l998-08-06 .
Precursor 6.5 2-Chloro-5-(5-chloro-1-difluoromethyl-2-methyl-lH-imida- -zol-4-yl)aniline 7 g (22 mmol) of 5-chloro-4-(4-chloro-3-nitrophenyl)-1-difluo-romethyl-2-methyl-lH-imidazole were dissolved in 200 ml of meth-anol with heating. This solution was added dropwise to a suspen-sion of 3.6 g (65 mmol) of iron powder in 150 ml of glacial acetic acid, stirred at reflux temperature. After 3 hours, the reaction mixture was poured into 500 ml of water. A further 500 ml of ethyl acetate were added to the mixture, whereupon the iron residues were filtered off. The aqueous phase was separated off and mixed with another 500 ml of ethyl acetate. The combined or-ganic phases were washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate and finally con-centrated. To 1~ ~ve the re-~;n;ng acetic acid, the crude product was treated with 100 ml of toluene, whereupon the mixture was again concentrated to dryness. Yield: 5.7 g.
20 lH NMR (270 MHz; in CDCl3): ~ [ppm] = 2.60 (s,3H), 4.13 (s,2H), 7.12 (t,lH), 7.15-7.35 (m,3H).
Example 7 Dimethyl l-bromo-2-t2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-Z5 1,3-dioxo-2H-isoindol-2-yl)phenyl]ethylphosphonate (No. IEc.860) Following the procedure described in Example 5 and using 21.2 g (0.16 mol) of dimethyl vinylphosphonate, 1.8 g (8 mmol) of copper(II) bromide, 1.1 g (11 mmol) of tert-butyl nitrite and 30 2.0 g (6.8 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)An;l;ne, 0.7 g of the above product of value is obtA; n~ .
35 Example 8 Dimethyl l-chloro-2-(2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)ethylphosphonate (No. IEb.860) Following the procedure described in Example 5 and using 21.2 g 40 (0.16 mol) of dimethyl vinylphosphonate, 1.1 g (8 mmol) of copper( II ) chloride, 1.1 g (11 mmol) of tert-butyl nitrite and 2.0 g (6.8 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)aniline, 1.0 g of the above product of value is obt~; ne~ .
- 0050/46586 CA 0224~6~9 1998-08-06 Example 9 Dimethyl l--chloro--2--[2--chloro--5--(3--chloro--4,5,6,7-tetrahydro--2H--indazol-2--yl)phenyl]ethylphosphonate(No. IGb.2) 5 Following the procedure described in Example 5 and using 42.4 g (0.31 mol) of dimethyl vinylphosphonate, 2.2 g (16 mmol) of copper(II) chloride, 2.2 g (22 mmol) of tert-butyl nitrite and 4.0 g (14 mmol) of 2--chloro--5--(3--chloro--4,5,6,7--tetrahydro--2H-indazol--2--yl)Anil;ne~ 0.8 g of the above product of value is 10 obtA;ne~.
Example 10 Dimethyl l--chloro--2--t2,4-dichloro--5-(4--chloro-5-difluoromethoxy--15 1--methyl--lH--pyrazol--3--yl)phenyl]ethylphosphonate(No. IBb.431) Following the procedure described in Example 5 and using 32.6 g (0.24 mol) of dimethyl vinylphosphonate, 3.6 g (26 mmol) of copper(II) chloride, 2.6 g (25 mmol) of tert-butyl nitrite and 20 13.6 g (24 mmol) of 2,4-dichloro-5-(4-chloro-5-difluoromethoxy-l--methyl-lH--pyrazol--3--yl)An;l;ne~ 3.6 g of the above product of value are obtAine~l.
Example 11 25 Dimethyl 1-chloro--2--(2-chloro-5--(1-methyl--6--trifluoromethyl--2,4(1H,3H)-pyrimi~inerlion--3--yl)phenyl)ethylphosphonate (No. IAb.2) Following the procedure described in Example 5 and using 17.9 g 30 (0.13 mol) of dimethyl vinylphosphonate, 0.9 g (7 mmol) of copper(II) chloride, 0.65 g (6.5 mmol) of tert-butyl nitrite and C' 2.0 g (6.3 mmol) of 2--chloro-5--(1--methyl--6--trifluoromethyl--- 2,4(1H,3H)--pyrimi~lineAion--3--yl)Anilin~ 1.0 g of the above product of value is obtAine~l.
Example 12 Dimethyl l-chloro--2--(2--chloro--4--fluoro--5--tl--methyl--4,5--di--(trifluoromethyl)--lH-pyrazol--3--yl)phenyl)ethylphosphonate 40 (No. IDb.860) Following the procedure described in Example 5 and using 13.1 g (96 mmol) of dimethyl vinylphosphonate, 0.7 g (5 mmol) of copper(II) chloride, 0.5 g (5 mmol) of tert-butyl nitrite and 45 1.2 g (4.6 mmol) of 2--chloro-4--fluoro--5--(1--methyl--4,5--di--- (trifluoromethyl)--lH--pyrazol--3--yl)aniline,0.6 g of the above product of value is obtAine~l.
-~ 0050/46586 CA 0224~6~9 1998-08-06 , Example 13 Diethyl l-chloro-2-[2-chloro-5-(4-chloro-S-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyllethylphosphonate (No. IBb.861) Following the procedure described in Ex_mple 5 and using 12.5 g (85 mmol) of diethyl vinylphosphonate, 0.7 g (5 mmol) of copper(II) chloride, 0.5 g (5 mmol) of tert-butyl nitrite and 1.5 g (4.6 mmol) of 2-chloro-4-fluoro-5-(4-chloro-5-difluoro-10 methoxy-1-methyl-lH-pyrazol-3-yl)An;lin~, 0.6 g of the above product of value is obtA i neA .
Example 14 15 Diethyl l-bromo-2-(2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyl)ethylphosphonate (No. IBc.861) Following the procedure described in Example 5 and using 12.5 g 20 (85 mmol) of diethyl vinylphosphonate, 1.1 g (5 mmol) of copper(II) bromide, 0.5 g (5 mmol) of tert-butyl nitrite and 1.5 g (4.6 mmol) of 2-chloro-4-fluoro-5-(4-chloro-5-difluoro-methoxy-l-methyl-lH-pyrazol-3-yl)Aniline~ 0.8 g of the above product of value is obtA;ne~.
Example 15 Diethyl 2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate (No. ICg.861) 30 Following the procedure described in Example 1 and using 0.45 g 1.5 mmol) of tetraethyl methAneAiphosphonate, 36 mg (1.5 mmol) of sodium hydride and 0.5 g (1.5 mmol) of 2-chloro-5-(4-chloro-l-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorobenz~ hyde, 0.4 g of the above product of value is obtA i neA .
Example 16 Diethyl 2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.3) Following the procedure described in Example 1 and using 0.5 g (1.7 mmol) of tetraethyl methaneAiphosphonate, 40 mg (1.7 mmol) of sodium hydride and 0.5 g (1.7 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 45 0.2 g of the above product of value is obt~; neA .
~ 0050/46586 CA 0224~6~9 1998-08-06 .
Example 17 Diethyl 2-(2-chloro-4-fluoro-S-(1,3,4,5,6,7-hexahydro-1,3-dioxo- -2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.861) 5 Following the procedure described in Example 1 and using 0.5 g (1.7 mmol) of tetraethyl me~h~ne~;phosphonate, 39 mg (1.7 mmol) of sodium hydride and 0.5 g (1.6 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydlo 1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 0.4 g of the above product of value is obt~;ne~.
G
Example 18 Diethyl 2-t2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)-phenyl]vinylphosphonate (No. IFg.3) Following the procedure described in Example 1 and using 0.55 g (1.9 mmol) of tetraethyl me~h~ne~;rhosphonate, 45 mg (1.9 mmol) of sodium hydride and 0.5 g (1.9 mmol) of 2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)h~n~ ehyde~ 0.5 g of 20 the above product of value is obtAine~. M.p.: 93-94~C.
Example 19 Diethyl 2-(2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimi~;ne~;on-3-yl)phenyl)vinylphosphonate (No. IAg.3) Following the procedure described in Example 1 and using 0.73 g (2.5 mmol) of tetraethyl methAne~;phosphonate, 57 mg (2.4 mmol) of sodium hydride and 0.5 g (1.5 mmol) of 2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimidinedion-3-yl)benzaldehyde, 30 0.4 g of the above product of value is obt~ine~.
Example 20 Diethyl 2-(2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-35 pyrimi~;ne~;on-3-yl)vinylphosphonate (No. IAg.432) Following the procedure described in Example 1 and using 0.7 g (2.3 mmol) of tetraethyl meth~ne~;rhosphonate, 52 mg (2.3 mmol) of sodium hydride and 0.5 g (1.4 mmol) of 2,4-dichloro-5-40 (1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimi~;ne~;on-3-yl)-benzaldehyde, 0.5 g of the above product of value is obtained.
.
OOSO/46586 CA 0224~6~9 1998-08-06 Precursor 20.1 2,4-Dichloro-5-isocyanatobenzaldehyde (O-ethyl)oxime 65.3 g (0.28 mol) of 5-amino-2,4-dichlorobenzaldehyde (O-ethyl)-5 oxime (obt~in~hle by the process given for precursors 28.1-28.3) and 60.9 g (0.31 mol) of diphosgene were reacted in the m~nner described for precursor 3.1. Yield: 72.9 g.
Precursor 20.2 2,4-Dichloro-5-(6-trifluoromethyl-2,4(1H,3H)-pyrim;~ine~ion-3-yl)benzaldehyde (O-ethyl)oxime 9.2 g (0.31 mol) of sodium hydride, 51.3 g (0.28 mol) of ethyl 15 3-amino-4,4,4-trifluorocrotonate and 72.6 g (0.28 mol) of 2,4-dichloro-5-isocyanatohen7-aldehyde (O-ethyl)oxime were reacted f in the m~nn~r described for precursor 3.2. Yield: 72.0 g;
m.p.: 205-209~C.
20 Precursor 20.3 2,4-Dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrim;~i n~ -dion-3-yl)benzaldehyde (O-ethyl)oxime 69.3 g (0.175 mol) of 2,4-dichloro-5-(6-trifluoromethyl-25 2,4(lH,3H)-pyri i~ine~ion-3-yl)~en 7.~1 dehyde (O-ethyl)oxime, 26.6 g (0.19 mol) of potassium carbonate and 27.3 g (0.19 mol) of methyl iodide were reacted in the ~-nner described for precursor 3.3. Yield: 69.0 g; m.p.: 140-143~C.
Precursor 20.4 2,4-Dichloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimi~in~-dion-3-yl)benzaldehyde 35 61.5 g (0.15 mol) of 2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyr;mi~in~ion-3-yl)benzaldehyde (O-ethyl)oxime were reacted in the m-nner described for precursor 3.4. Yield: 50.0 g;
m.p.: 117-120~C.
40 Example 21 Diphenyl 2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.56) 2.6 g (5.2 mmol) of diphenyl (triphenylphosphorany~i~ene)methane-45 phosphonate and 1 g (3.4 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexa-hydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde were dissolved in 100 ml of toluene, whereupon the mixture was refluxed for - 0050/46586 CA 0224~6~9 1998-08-06 .
4 hours. The reaction mixture was subsequently concentrated. The crude product obtained as residue was purified by means of silica gel chromatography (eluent: h~n~/ethyl acetate = 2:1) followed by crystallization from he~Ane/ethyl acetate. Yield: 0.8 g.
s Example 22 Diethyl l-chloro-2-(2-chloro-S-(4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate (No. ICh.861) Following the procedure described in Example 2 and using 37.3 g (0.15 mol) of diethyl trichloromethanephosphonate, 42 ml (67 mmol) of a 1.6-molar butyllithium solution and 10 g (29 mmol) lS of 2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorobenzaldehyde, 12.8 g of the above product of value are obtained.
Example 23 20 Diethy~ 1-chloro-2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEh.3) Following the procedure described in Example 2 and using 4.4 g (17 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) 25 of a 1.6-molar butyllithium solution and 1 g (3.5 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)-benzaldehyde, 0.6 g of the above product of value is obtAine~.
Example 24 30 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEh.861) Following the procedure described in Example 2 and using 4.1 g 35 (16 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (3.2 mmol) of 2-chloro-4-fluoro-5(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 0.6 g of the above product of value is obtained.
- 0050/46586 CA 0224~6~9 1998-08-06 .
~ 170 Example 25 Diethyl l-chloro-2-(2-chloro-5-(3,4-dimethyl-lH ~yllole-2,5-dion- .
l-yl)-phenyl)vinylphosphonate (No. IFh.3) 5 Following the procedure described in Example 2 and using 4.8 g (19 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (3.8 mmol) of 2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)benzaldehyde, 0.4 g of the above product of value is obt~; n~
Example 26 Diethyl 1-chloro-2-t2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyr; mi ~; ne~; on-3-yl)phenyl]vinylphosphonate Following the procedure described in Example 2 and using 4 g - (16 mmol) of diethyl trichlorometh~nephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 0.7 g (2.8 mmol) of 20 2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyri~;~;n~;on- .
3-yl)benzaldehyde, 0.5 g of the above product of value is obt~ine~.
Example 27 25 Diethyl l-chloro-2-t2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyr; m; ~; neA; o~-3-yl)phenyl]vinylphosphonate (No. IAh.432) Following the procedure described in Example 2 and using 4 g 30 (16 m.mol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (2.7 mmol) of L 2,4-dichloro-5-(l-methyl-6-trifluoromethyl-2,4(1H,3H)-pyr~ ;ne ~- dion-3-yl)benzaldehyde, 0.3 g of the above product of value is obt~;ne~.
Example 28 Diethyl l-chloro-2-t2,4-dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl]vinylphosphonate (No. IEh.432) Following the procedure described in Example 2 and using 1.5 g (6 mmol) of diethyl tr;chlo~omethanephosphonate, 1.8 ml (2.9 mmol) of a 1.8-molar butyllithium solution and 0.3 g (o.9 mmol) of 2,4-dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-45 2H-isoindol-2-yl)benzaldehyde, 0.3 g of the above product of value is obt~; ne~ .
- 0050/46586 CA 0224~6~9 1998-08-06 , Precursor 28.1 2,4-Dichloro-5-nitrobenzaldehyde A solution of 125 g of nitric acid in 153 g of sulfuric acid 5 which had been prepared with ice-cooling at (-5)~C was added dropwise to a solution of 262.5 g (1.5 mol) of 2,4-dichlorobenzaldehyde in 560 ml of sulfuric acid. After the reaction mixture had been stirred for 2 hours at 10~C, it was poured onto 4 kg of ice. The resulting solids were subsequently 10 separated off, washed with water and dissolved in 2 1 of dichloromethane. The resulting solution was washed with saturated aqueous sodium hydrogen carbonate solution, then dried over magnesium sulfate and finally concentrated. Yield: 329.5 g;
m.p.: 61-63~C.
_ Precursor 28.2 2,4-Dichloro-5 - nitroh~n 7 A ldehyde (O-methyl)oxime 20 93.1 g (0.223 mol) of methoxyamine hydrochloride (20% strength by weight solution in water) were treated with 100 ml of water and 18.7 g (0.223 mol) of sodium hydrogen carbonate. A solution of 44 g (0.2 mol) of 2,4-dichlorobenzaldehyde in 200 ml of toluene were added dropwise to tnis mixture. l~ne mixture was subsequently 25 heated for 5 hours at 50~C. The organic phase was then separated off. After washing with water and saturated aqueous sodium chloride solution, the resulting crude-product solution was dried over magnesium sulfate and finally concentrated. Yield: 39.2 g;
m.p.: 77-79~C.
Precursor 28.3 5-Amino-2,4-dichlorobenzaldehyde (O-methyl)oxime 16.8 g (0.3 mol) of iron powder were dissolved in 130 ml of methanol and 100 ml of acetic acid. A solution of 24.9 g (0.1 mol) of 2,4-dichloro-5-nitrobenzaldehyde (O-methyl)oxime in 100 ml of acetic acid and 100 ml of methanol was added dropwise to this solution at 70~C. The reaction mixture was then heated for 1 hour at 75-80~C, whereupon it was poured onto 3 kg of ice. The 40 product of value was subsequently extracted with 2 1 of dichloromethane. The organic phase was dried over magnesium sulfate and finally concentrated. The crude product was purified by stirring with a small amount of pentane. Filtration gave 18.5 g of product of value. M.p.: 129-132~C.
- ~ 0050/46586 CA 0224~6~9 l998-08-06 Precursor 28.4 2,4-Dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl) benzaldehyde (O-methyl)oxime 5 18 g (82 mmol) of 5-amino-2,4-dichlorobenzaldehyde (o-methyl)oxime were added to a solution of 12.5 g (82 mmol) of 3,4,5,6-tetrah~dLophthalic anhydride in 300 ml of acetic acid, whereupon the mixture was stirred for 15 hours at reflux temperature. The reaction mixture was subsequently poured into 10 1 l of water. The product was then extracted with 300 ml of methyl tert-butyl ether. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate and finally concentrated. The residue was purified by means of silica gel chromatography (eluent: h~ne/ethyl acetate 15 = 4:1). Yield: 20.9 g; m.p.: 122-124~C.
Precursor 28.5 2,4-Dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl) 20 benzaldehyde 9 ml of a 37% strength by weight aqueous formaldehyde solution and 9 ml of concentrated hydrochloric acid were added to a solution of 10.6 g (30 mmol) of 2,4-dichloro-25 5-(1,3,4,5,6,7-hexah~dlo 1,3-dioxo-2H-isoindol-2-yl)ben~ ehyde (O-methyl)oxime in 45 ml of acetic acid. The mixture was subsequently heated for 1 hour at 50-60~C, whereupon the reaction mixture was poured into 300 ml of ice-water. The product was extracted from the resulting mixture using 200 ml of 30 dichloromethane. The extract was dried over magnesium sulfate and then concentrated. The ~esidue was purified by means of silica gel chromatography (eluent: heY~ne/ethyl acetate = 4:1). Yield:
5.2 g; 1H NMR (270 MHz; in CDCl3): atppm] s 1.85 (s, 4H), 2.45 (s, 4H), 7.67 (s, lH), 7.81 (s, lH), 10.40 (s, lH).
Example 29 Diisopropyl 2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)ethylphosphonate (No. ICa.863) 40 A suspension of 6 g (11 mmol) of diisopropyl 1-chloro-2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate, 1.1 g (13 mmol) of sodium acetate and 50 mg of 5% palladium on active charcoal in 100 ml of ethanol was treated with 5 bar of hydrogen. After the mixture had 45 been stirred for one day, the catalyst was Lc..~ved by filtration.
The filtrate was concentrated. 100 ml of water and 100 ml of ethyl acetate were added to the resulting residue. The organic - ~ 0050/46586 CA 0224~6~9 1998-08-06 .
173 _ phase was separated off, dried over magnesium sulfate and finally concentrated. Silica gel chromatography of the residue (eluent:
h~n~/ethyl acetate = 3:1) first gave 0.2 g of the product of value and then 1.5 g of diisopropyl 5 2-t5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl]ethyl-phosphonate.
Example 30 l-Chloro-2-(2-chloro-5-(4-chloro- 1-methyl-5-trifluoromethyl-10 lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonic acid (No. ICh.859) A solution of 1 g (2 mmol) of diethyl 1-chloro-2-t2-chloro-15 5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluoro-phenyl]vinylphosphonate~ 0.97 g (5.9 mmol) of potassium iodide and 0.6 g (5.9 mmol) of chlorotrimethylsilane in 20 ml of acetonitrile was heated for 3 hours at 50-60~C. The mixture was subsequently concentrated. The residue was treated with 50 ml of 20 water and 50 ml of ethyl acetate. After the organic phase had been separated off and dried over magnesium sulfate, the mixture was concentrated. Yield: 0.7 g.
Example 31 25 1-Chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid (No. IBh.859~
Following the procedure described in Example 30 and using 11.4 g 30 (22.6 mmol) of diethyl 1-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl-phosphonate, 11.3 g (68 mmol) of potassium iodide and 7.8 g (67 mmol) of chlorotrimethylsilane, 9 g of the above product of value are obt~; n~A .
Example 32 l-Chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-(lH,3H)pyr; m; A; neA; on-3-yl)phenyl]vinylphosphonic acid (No. IAh.859 Eollowing the procedure described in Example 30 and using 5 g (9.6 mmol) of diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr; m; ~; neA;on-3-yl)phenyl]vinyl-45 phosphonate, 4.8 g (29 mmol) of potassium iodide and 3.1 g(29 mmol) of chlorotrimethylsilane, 4.5 g of the above product of value are obtained.
- ~ 0050146586 CA 022456S9 1998-08-06 .
Example 33 Dimethyl l-chloro-2-[2-chloro-5-(4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (~o.
ICh.860) 0.7 g (5.5 mmol) of oxalyl chloride and one drop of dimethyl-formAm;~e were added to a solution of O.7 g (1.5 mmol) of l-chloro-2-l2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid in 30 ml of lO dichloromethane. After the evolution of gas had ceased, a solution of 2.3 g (15 mmol) of methanol and 0.6 g (8 mmol) of pyridine in 50 ml of dichloromethane was added dropwise to the resulting mixture. The reaction mixture was stirred for a further 2 hours and subsequently concentrated. The residue was treated 15 with 50 ml of water and 50 ml of ethyl acetate. The organic phase was dried over magnesium sulfate and then concentrated. The crude product was purified by means of siliga gel chromatography (eluent: h~YAne/ethyl acetate = 3:1). Yield: 0.25 g.
Example 34 2~ Chloro-2-[2-chloro-5-(4-chloro-l-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl)-2,1,3-phosph~;ox~n-2-one (No. ICh.1154) Following the procedure described in Example 33 and using l g (2.2 mmol) of l-chloro-2-t2-chloro-5-(4-chloro-1-methyl-S-tri-fluoromethyl--lH--pyrazol--3--yl)--4--fluorophenyl]vinylphosphoni~
acid, 0.7 g (5.5 mmol) of oxalyl chloride, 1.5 g (20 mmol) of 30 1,3-propAne~;ol and 0.8 g (10 mmol) of pyridine, 0.6 g of the above product of value is obt~ne~.
~_ Example 35 Dimethyl l-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-35 1-methyl-1~-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No. I8h.860) Following the procedure described in Example 33 and using 0.7 g (1.5 mmol) of 1-chloro-2-l2-chloro-5-(4-chloro-5-difluoromethoxy-40 1-methyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid, 0.7 g (5.5 mmol) of oxalyl chloride, 0.45 g (14 mmol) of methanol and 0.56 g (7.2 mmol) of pyridine, 0.3 g of the above product of value is obt~;ne~.
- 0050/46586 CA 0224~6~9 1998-08-06 .
175 _ Example 36 2-(1-Chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH--pyrazol-3--yl)--4-fluorophenyl]vinyl)-2,1,3-phosphA~l;oxan--2--one (No. IBh.1154) Following the procedure described in Example 33 and using 0.7 g (1.5 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-flUorophenyl]VinylphosphoniC acid, 0.7 g (5.5 mmol) of oxalyl chloride, 1 g (14 mmol) of 10 1,3-propanediol and 0.56 g (7.2 mmol) of pyridine, 0.3 g of the above product of value is obtA;ne~.
Example 37 S,S-Diethyl 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyldithiophosphonate f (No. IBh.1271) Following the procedure described in Example 33 and using 0.8 g 20 (1.8 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonic acid, 0.5 g (3.9 mmol) of oxalyl chloride, 1.0 g (18 mmol) of ethylmercaptan and 0.7 g (8.8 mmol) of pyridine, 0.5 g of the above product of value is obtA;ne~.
Example 38 2-(1-Chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl)-1,3-dimethylperhydro-2,1,3-phosphA~iA7in-2-one (No. IBh.1256) Following the procedure described in Example 33 and using 0.8 g ~1.8 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonic acid, 0.5 g (3.9 mmol) of oxalylchloride, 1.8 g (18 mmol) of 35 N,N'-dimethyl-1,3-~;; ;nopropane and 0.7 g (8.8 mmol) of pyridine, 0.34 g of the above product of value is obtained.
Example 39 40 Dimethyl l-Chloro-2-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl--2,4-(lH,3H)pyr;m;~l;nadion--3-yl)phenyl]vinylphosphonate (No. IAh.860) Following the procedure described in Example 33 and using 0.9 g 45 (1.9 mmol) of 1-chloro-2-[2-chloro-4-fluoro-5-(1-methyl-6-tri-fluoromethyl-2,4(1H,3H)pyrimi~;ne~;on-3-yl)phenyl]vinylphosphonic acid, 0.7 g (5.5 mmol) of oxalyl chloride, 0.6 g (19 mmol) of - 0050/46586 CA 0224~6~9 1998-08-06 methanol and 0.75 g (9.5 mmol) of pyridine, 0.2 g of the above product of value i5 obtained.
Example 40 5 Diisopropyl l-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-tri-fluoromethyl--2,4--(lH,3H)pyr;m;~;ne~;on--3--yl)phenyl]vinyl--phosphonate (No. IAh.863) .
10 0 4 g (15 mmol) of sodium hydride was added to a solution of 5.8 g (15 mmol) of tetraisopropyl chloromethane~;phosphonate in 100 ml of tetrahydrofuran. After the mixture had been stirred for 30 minutes, 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr;m;~;n~A;on-3-yl)benzaldehyde were 15 added. The mixture was subsequently stirred for 1 hour. The reaction mixture was then treated with 50 ml of water and 50 ml of ethyl acetate. The organic phase was separated off, dried over magnesium sulfate and finally concentrated. The crude product obtained was purified by means of MPLC on silica gel (eluent:
20 he~Ane/ethyl acetate = 2:1). Yield: 1.1 g.
Example 41 Diisopropyl l-bromo-2-12-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl--2,4--(lH~3H)pyr;m;c~;ne~l;on--3--yl)phenyl]Vinylphosphonate 25 (No- IAi.863) Following the procedure described in Example 40 and using 6.5 g (15 mmol) of tetraiso~Lo~yl b~ thAne~;rhosphonate, 0.4 g (15 mmol) of sodium hydride and 3.2 g (9 mmol) of 2-chloro-30 4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr;m;~;ne~;on-3-yl)benzaldehyde, 2.6 g of the above product of value are obtained.
Example 42 35 Diethyl 2-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyrimi~; ne~; on-3-yl)phenyl]-1-cyanovinylphosphonate (No. IAj.861) 40 A solution of 1.6 g (9 mmol) of diethyl cyanomethanephosphonate, 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl-2,4(lH,3H)pyr; m; ~; nedion-3-yl)benzaldehyder 0.6 ml of acetic acid and 0.18 ml of piperidine in 60 ml of toluene was refluxed for 6 hours, whereupon the mixture was concentrated. The 45 crude product obtA;n~ was purified by silica gel chromatography (eluent: hexane/ethyl acetate ~ 1:1). Yield: 1.8 g.
-~ 0050/46586 CA 0224~6~9 1998-08-06 .. . .
Example 43 Diethyl 1-~2-chloro-4-fluoro-S-(l-methyl-6-trifluoromethyl-2,4(1H,3H)pyrim;~ine~;on-3-yl)phenyl]prop-l-en-2-ylphosphonate (No. IAk.861) A solution of 10 ml (20 mmol) of a 2-molar solution of lithium diisopropylamide in 50 ml of tetrahydrofuran was cooled to (-60)~C
and at this temperature treated with 1.5 g (9 mmol) of diethyl ethanephosphonate, whereupon the mixture was stirred for 10 15 minutes. The mixture was subsequently cooled to (-70)~C, and 1 g (9.5 mmol) of chlorotrimethylsilane was added at this temperature. After the mixture had been stirred for a further 15 minutes, it was heated to (-20)~C and treated with 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-15 2,4(lH,3H)pyrimi~;n~;on-3-yl)benzaldehyde. Stirring was then continued for 2 hours at room t~ _e~ature. For working-up, the reaction mixture was treated with 10 ml of dilute hydrochloric acid. The product was extracted with ethyl acetate. Finally, the ethyl acetate phase was separated off, dried over magnesium 20 sulfate and concentrated. The crude product was purified by means of MPLC on silica gel (eluent: hexane/ethyl acetate = 1:2).
Yield: 0.2 g.
25 Example 44 Diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(5,6,7,8-tetrahydro-1,2,4-triazolot4,3-a]pyridine-3(2H)-on-2-yl)phenyl]vinyl-phosphonate (No. IKh.861) 30 1.4 g (16.8 mmol) of sodium acetate were added to a solution of 2 g (5.6 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-hydrazinophenyl)vinylphosphonate in 50 ml of acetonitrile.
After the mixture had been stirred for 30 minutes, it was cooled to 0~C and treated with 1.1 g (5.6 mmol) of methyl 35 2-iminopiperidine-1-carboxylate hydrochloride. The reaction mixture was subsequently stirred for 3 hours. It was then treated with 50 ml of water and 50 ml of ethyl acetate. The organic phase was separated off, dried over magnesium sulfate and finally concentrated.
The residue, which cont~;ne~ methyl 2-t2-(4-chloro-2-fluoro-5-t2-chloro-(2-diethylphosphoryl)vinyl]phenyl)hydrazin-1-yl-idene]piperidine-1-carboxylate, was dissolved in 50 ml of toluene and then treated with 0.1 ml of acetic acid. The mixture was 45 subsequently refluxed for 2 hours and then concentrated. The 0050/46~86 CA 0224~6~9 1998-08-06 , crude product obtained was purified by means of silica gel chromatography (eluent: ethyl acetate). Yield: 0.3 g.
Precursor 44.1 5 Diethyl l-chloro-2-(2-chloro-4-$1uorophenyl)vinylphosphonate (No. XXXIII.24) 462 ml (0.74 mol) of a 1.6-molar butyllithium solution (in 10 he~ne) were added to a solution, cooled to (-70)~C, of 408 g (1.6 mol) of diethyl trichloromethanephosphonate in 1.5 1 of tetrahydrofuran, whereupon the mixture was stirred for 1 hour at (-70)~C. 51 g (0.32 mol) of 2-chloro-4-fluorobenzaldehyde (dissolved in 200 ml of tetrahydrofuran) were subsequently added 15 dropwise to the mixture. The reaction mixture was then allowed to come to approximately 20~C, at which t- ~rature it was treated with 10 ml of water. Finally, the mixture was concentrated (under a high vacuum during the last phase). To purify the crude product, it was suspen~PA in 50 ml of hexane, and the solids were 20 filtered off. Concentration of the filtrate gave 47.5 g of the product of value.
H NMR (270 ~Hz; in CDCl3): ~ tppm] s 1.20-1.40 (m,6H), 4.10-4.30 (m,4H), 6.95-7.20 (m,2H), 7.45-7.95 (m,2H).
25 Precursor 44.2 Diethyl l-chloro-2-(2-chloro-4-fluoro-5-nitrophenyl)vinyl-phosphonate (~o. XXXII.36) 47.5 g (0.16 mol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-30 phenyl)vinylphosphonate were dissolved in 320 ml of co~centrated nitric acid at (-40)~C, whereupon the mixture was stirred for 1 hour. The reaction mixture was subsequently stirred into ~_ 2.5 1 of ice-water. The product was then extracted with dichloromethane. The organic phase was washed with saturated 35 aqueous sodium chloride solution, dried over magnesium sulfate and finally concentrated. The crude product was purified by means of MPLC on silica gel (eluent: hPx~ne/ethyl acetate = 2:1).
Yield: 33 g; lH NMR (270 MHz; in CDCl3): ~ lppml = 1.30-1.45 (m,6H), 4.10-4.30 (m,4H), 7.35-7.85 (m,2H), 8.30-8.70 (m,lH).
Precursor 44.3 Diethyl l-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinyl-phosphonate (No. XXXI.36) 17.5 g (47 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-nitrophenyl)vinylphosphonate were added at 60-65~C to a _ - OOS0/46586 CA 0224~6~9 1998-08-06 .
suspension of 13.1 g (0.24 mol) of iron powder in 40 ml of ethanol and 88 ml of acetic acid, whereupon the mixture was stirred for 2 hours at reflux temperature. The mixture was subsequently treated with 200 ml of ethyl acetate. The resulting 5 suspension was filtered through a Rieselguhr bed. The filtrate was then concentrated. The residue was dissolved in 200 ml of ethyl acetate. The organic phase was then washed with water, dried over magnesium sulfate and finally concentrated. Yield:
14.8 g; lH NMR (270 MHz; in CDCl3): ~ [ppm] = 1.41 (t,6H), 3.90 10 (s,2H), 4.20 (m,4H), 7.09 (d,lH), 7.37 (d,lH), 7.80 (d,lH).
Precursor 44.4 ~iethyl l-chloro-2-(2-chloro-4-fluoro-5-hydrazinophenyl)vinyl-phosphonate (No. XXVIII.36) ~_ 2.5 g (7.3 mmol) of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinylphosphonate were dissolved in 13.1 g of concentrated hydrochloric acid by briefly heating to 60~C. The 20 resulting solution was cooled to 0~C and treated with a solution of 0.5 g (7.3 mmol) of sodium nitrite in 1.5 ml of water. After the mixture had been stirred for 1 hour, a solution of 4.15 g (18.4 mmol) of tin(II) chloride dihydrate in 2.6 ml of concentrated hydrochloric acid was added dropwise. The mixture 25 was subsequently stirred for 2 hours at approximately 20~C. It was then diluted with 100 ml of water. The solids were filtered off.
The filtrate was rendered ~kAl;ne by adding 50 % strength sodium hydroxide solution. The product was extracted from the aqueous phase using three portions of 50 ml of dichloromethane. The 30 combined organic phases were washed with water, dried over magnesium sulfate and finally concentrated. Yield: 2 g; lH NMR
(270 MHz; in CDCl3): ~ [ppm] = 1.40 (t,6H), 3.60 (s,2H), 4.22 (m,4H), 5.48 (s,lH), 7.07 (d,lH), 7.73 (d,lH), 7.85 (d,lH).
35 Example 45 Diethyl l-chloro-2-(2-chloro-4-fluoro-5-[(3-methyl-4-trifluoro-methyl-2(3H)-thiazolylidene)amino]phenyl)vinylphosphonate (No. ILh.861) 40 0.3 g (3.5 mmol) of sodium acetate and 0.6 g (2.9 mmol) of 3-bromo-1,1,1-trifluoroacetone were added to a solution of 1.2 g (2.9 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-t(methyl-aminothiocarbonyl)amino~phenyl)vinylphosphonate in 50 ml of toluene, whereupon the mixture was refluxed for 1 week. The 45 reaction mixture was then washed with water, dried over magnesium sulfate and concentrated. The crude product was purified by means - 0050/46586 CA 0224~6~9 l998-08-06 of silica gel chromatography (eluent: hexane/ethyl acetate =
1:1). Yield: 0.2 g.
Precursor 45.1 5 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-[(methylaminothio-carbonyl)amino]phenyl)vinylphosphonate (No. XXXV.36) 1.2 g (16.4 mmol) of methyl isothiocyanate were added to a solution of 3 g (8.7 mmol) of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinylphosphonate in 50 ml of ethanol.
After the mixture had been stirred for 8 hours at reflux temperature, it was concentrated. The crude product was purified by means of silica gel chromatography (eluent: h~xAne/ethyl 15 scetate = 1:1). Yield: 1.3 g; 1H NMR (270 MHz; in CDCl3): ~ tppm]
= 1.41 (t,6H), 3.15 and 3.17 (2s, together 3H), 4.22 (m,4H), 6.40 ~ (s,lH), 7.29 (d,lH), 7.60 (s,lH), 7.81 (d,lH), 8.16 (s,lH).
t Example 46 20 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-((tetrahydro-3-oxo-lH,3H-[1,3,4]-~h; AA i A ~olo~3,4-a]pyridazin-1-ylidene)amino)phenyl)vinyl-phosphonate (No. IMh.861) 2.2 g (28 mmol) of pyridine and 1.4 g (7 mmol) of diphosgene were 25 added to a solution of 3.3 g (7 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-5-((hexahyd u~y ;~A~;n-1-ylthiocarbonyl)-amino)phenyl)vinylphosphonate in 100 ml of dichloromethane, wheLeu~on the mixture was stirred for 1 hour. The reaction mixture was subsequently washed with water, dried over magnesium 30 sulfate and concentrated. The crude product was purified by means of silica gel chromatography (eluent: he~Ane/ethyl acetate =
1:2). Yield: 1 g.
Precursor 46.1 35 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-isothiocyanatophenyl)-vinylphosphonate (No. XL.36) 1.1 g (9.7 mmol) of thiophosgene and a solution of 3 g (8.7 mmol) 40 of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinyl-phosphonate in 15 ml of dichloromethane were added to a solution of 1.6 g (19 mmol) of sodium hydrogen carbonate in 10 ml of water and 10 ml of dichloromethane, whereupon the mixture was stirred for 5 hours. The reaction mixture was subsequently washed with 45 water, dried over magnesium sulfate and concentrated. Yield: 3 g;
lH NMR (270 MHz; in CDCl3): ~ tppm] = 1.40 (t,6H), 4.22 (m,4H), 7.30 (d,lH), 7.74 (d,lH), 7.78 (d,lH).
-~ OOS0/46586 CA 0224~6~9 1998-08-06 , 181 _ Precursor 46.2 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5[(hexahydropyridazin-l-yl-thiocarbonyl)amino]phenyl)vinylphosphonate (No. xx~TxA~36) 5 A solution of 3 g (8.7 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-S-isothiocyanatophenyl)vinylphosphonate in 20 ml of tetrahydrofuran was added to a solution of 0.8 g (9.3 mmol) of hexahydropyri~A7;ne in 20 ml of tetrahydrofuran, whereupon the mixture was stirred for 16 hours. The reaction mixture was then lO concentrated. The residue was treated with 50 ml of ethyl acetate. Finally, the organic phase was washed with water, dried over magnesium sulfate and concentrated. Yield: 3.3 g. The crude product was further reacted without further purification.
Example 47 Diethyl 1-chloro-2-(2-chloro-5-t(6,7-dihydro-6,6-dimethyl-3H,5H--pyrrolo--t2,1--c]tl,2,4]th;A~;A7-ol--3--yl;~ene)amino]--4-fluorophenyl)vinylphosphonate (No. INh.861) 10.5 g (26.4 mmol) of a 10 % strength by weight sodium hydlo~ide solution were added at 0-5~C to a solution of 1.3 g (8.8 mmol) of 5-amino-3,4-dihydro-3,3-dimethyl-2H ~ylLole hydrochloride in 50 ml of dichloromethane. After the mixture had been stirred for 25 one hour, it was treated with 2.5 g (6.5 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-5-isothiocyanatophenyl)vinyl-phosphonate. The reaction mixture was subsequently stirred for 3 hours and then cooled to (-20)~C and treated with 1.2 g (6.9 mmol) of bromine. In order to react all reactants as 30 completely as possible, stirring was cont;n~eA for 16 hours at approximately 20~C. Finally, the organic phase was separated off, dried over magnesium sulfate and concentrated. The crude product was purified by means of silica gel chromatography (eluent:
h~Ane/ethyl acetate - 1:1). Yield: 1.7 g.
Example 48 Diisopropyl 1-bromo-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No. Isi~863) and diisopLo~yl 2-t2-chloro-5-(4-chloro-40 5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]-ethynylphosphonate (No. IBn.863) Following the procedure described in Example 40 and using 3.4 g (8 mmol) of tetraisopropyl b~ Lhanediphosphonate, 0.2 g 45 (8 mmol) of sodium hydride and 1.6 g (4 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoro-benzaldehyde, a crude product is obt~;ne~ whose silica gel -~ 0050~46586 CA 0224~6~9 l998-08-06 chromatography first revealed 0.5 g of diisopropyl 1-bromo-2-l2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH ~yl dZOl -3-yl)-4-fluorophenyl]vinylphosphonate followed by 0.4 g of diisopropyl 2-l2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-5 lH-pyrazol-3-yl)-4-fluorophenyl]ethynylphosphonate.
Example 49 Diethyl 2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fiuorophenyl]-1-cyanoethylphosphonate 10 (No. IBd.86l) 0.66 g (3.7 mmol) of diethyl cy~n~ -~hanephosphonate was added to a suspension of 80 mg (3.4 mmol) of sodium hydride in 50 ml of 15 tetrahydrofuran. After the mixture had been stirred for 10 minutes, it was treated with 1 g (2.5 mmol) of 2-chloro-5-~4-chloro-5-difluoromethoxy-1-methyl-lH ~yLazol-3-yl)-4-fluor C benzyl bromide. The mixture was subsequently stirred for 16 hours. The reaction mixture was subsequently concentrated.
The residue was treated with 100 ml of water and 100 ml of ethyl acetate. After the phases had been mixed, the organic phase was separated off, dried over magnesium sulfate and concentrated.
The crude product was purified by silica gel chromatography (eluent: ~e~ne/ethyl acetate - 4:1). Yield: 0.7 g.
Example 50 Methyl 3-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]-2-(diethylphosphoryl)propionate (No. IBf.861) Following the procedure described in Example 49 and using 80 mg (3.4 mmol) of sodium hydride, 0.78 g (3.7 mmol) of methyl diethylphosphorylacetate and 1 g (2.5 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoro-35 benzyl bromide, 0.7 g of the desired product of value were obt~;ne~.
In addition to the subst~nces described above, further aromatic phosphonic acid derivatives of the form~ I which were, or can 40 be, prepared in a similar ~nne~ are listed in Tables 9-20 below:
Table 9 - (/ \~= O
,~N yl IA {R3 = Cl, D
~ ~ Eth--P -- y2R1 R5 - ~pl~ O
R9 = (~F8 }
Cl y3R2 w ~
-Eth- -P(=Yl)(Y2RI)(Y3R2) M.p. / IH NMR (o in [ppm]) / MS [m/z]
IAb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 3.13 (dt, lH),3.56 (s, 3H), 3.66 (ddd, lH), 3.83 (d, 3H), 3.90 (d, 3H), 4.28 (dt, lH), 6.37 (s, lH), 7.12 (dd, lH), 7.21 (d, lH), 7.53 (d, lH) lAg.3 H -CH=CH- p(=O)(OC2Hs)2 96-98oc IAg.432 Cl -CH=CH- _p(=O)(Oc2Hs)2 150-lS~C
IAg.861 F -CH=CH- _p(=O)(OC2Hs)2 1.37 (t, 6H), 3.57 (s, 3H), 4.16 (quint, 4H), 6.20 (dd, lH), 6.39 (s, lH), 7.36 (d, lH), 7.52 (d, lH), 7.77 (dd, lH) No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (o in [ppm]) / MS [m/z] ~
IAh.3 H -CH=C(a)- -P(=o)(oc2Hs)2 1.19 and 1.40 (2t, together 6H), 3.54 and 3,56 (2s, together 3H), 4.22 (m, 4H), 6.34 and 6.38 (2s, together lH), 7.15 and 7.20 (2dd, together lH), 7.48 and 7.81 (2d, together G:~
lH), 7.50 and 7.90 (2d, together lH), 7.52 and 7.59 (2d, together lH) lAh.432 a -CH=C(a)- _p(=O)(OC2Hs)2 118-121~C
lAh.859 F -CH=C(CI)- -P(=O)(OH)2 3.42 (s, 3H), 6.60 (s, lH), 7.59 (d, lH), 7.86 (d, lH), 8.03 (d, lH) D
IAh.860 F -CH=C(a)- _p(=O)(OCH3)2 3.59 (s, 3H), 3.87 (d, 6H), 6.39 (s, lH), 7.40 (d, lH), 7.87 (d~ lH)~ 7-92 (d~ lH) IAh.861 F -CH=C(a)- -P(=o)(oc2Hs)2 518 [M]+, 483 [M-CI]+ '~
IAh.862 F -CH=¢(CI)- _p(=o)[o-(n-c3H7)]2 0.99 (t, 6H), 1.76 (sext, 4H), 3.58 (s,3H), 4.10 (quint, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.86 (d, lH), 7.93 (d, lH) O
IAh.863 F -CH=¢(a)- _p(=o)[OCH(CH3)2]2 1.36 (d, 6H), 1.41 (d, 6H), 3.58 (s, 3H), 4.77 (m, 2H), 6.38 ~
(s, lH), 7.37 (d, lH), 7.86 (d, lH), 7.90 (d, lH) lAh.864 F -CH=¢(a)- -P(=O)[O-(n-(iHs)]2 0.95 (t, 6H), 1.43 (sext, 4H), 1.72 (quint, 4H), 3.58 (s, 3H), 4.13 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.85 (d,lH), 7.93 (d, lH) IAh.865 F -CH=¢(a)- _p(=o)[ocH2-cH(cH3)2]2 0.98 (d, 12H), 2.03 (m, 2H),3.59 (s, 3H), 3.91 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.85 (d, lH), 7.93 (d, lH) No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (~ in [ppm]) / MS [m/z] ~
IAh.866 F -CH=C(CI)- _p(=o)[ocH(cH3)-c2Hs]2 0.95 and 0.98 (2t, together 6H), 1.35 and 1.40 (2d, together 6H), 1.65-1.80 (m, 4H), 3.58 (s,3H), 4.57 ,~
(m, 2H), 6.39 (s, lH), 7.39 (d, lH), 7.87 (d, lH), 7.89 '"
(d, lH
IAh.867 F -CH=C(CI)- _p(=o)(ocH2-cF3)2 3.57 (s, 3H), 4.50 (m, 4H), 6.38 (s, lH), 7.42 (d, lH), 7.94 (d, lH), 7.96 (d, lH) IAh.870 F -CH=C(CI)- -P(=O)(OCH2-CH2-OCH3)2 3.39 (s, 6H),3.56 (s, 3H),3.66 (t, 4H), 4.29 (m, 4H), 4.50 ~, (m, 4H), 6.38 (s, lH), 7.40 (d, lH), 7.88 (d, lH), 7.92 D
(d~ lH) IAh.890 F -CH=C(CI)- -P(=O)(OCH2-CH=CH2)2 3.57 (s, 3H),4.65 (m, 4H), 5.27 (d, 2H), 5.42 (d, 2H), 5.97 (m, 2H), 6.39 (s, lH), 7.39 (d, lH), 7.87 (d, lH), 7.92 ~O
(d, lH) ~-1Ah.894 F -CH=C(CI)- -P(=o)(ocH2-c- CH)2 2.64 (t, 2H), 3.57 (s, 3H), 4.82 (dd,4H), 6.38 (s, lH), 7.40 ~n ~
(d~ lH), 7.92 (d, lH), 7.95 (d, lH) ~O
IAh.896 F -CH=C(CI)- ~P(=o)(ocHrco-ocH3)2 3.58 (s, 3H), 3.81 (s, 6H), 4.74 (dd, 2H), 4.83 (dd, 2H), 6.38 (s, lH), 7.39 (d, lH), 7.84 (d, lH), 7.86 (d, lH) IAh.914 F -CH=C(CI)- -P(=O)(O-phenyl~ 3.58 (s,3H), 6.38 (s, lH), 7.15-7.40 (m, llH), 7.87 (d, lH), 7.99 (d, lH) IAh.1154 F -CH=C(CI)- _P(=o)(o-cH2-cH2-cH2-o) 2.08 (m, lH), 2.30 (m, lH), 3.57 (s, 3H), 4.58 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.82 (d, lH), 7.87 (d, lH) IAh.1155 F -CH=C(CI)- _p(=o)(o-cH2-c(cH3)2-cH2-o) 530 [M]+, 495 [M-CI]+
r. ~ .
No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (~ in [ppm]) / MS [m/z] ~
IAh.1256 F -CH=C(CI)- -P(=o)[N(cH3)-cH2-cH2-cH2-N(cH3)] 1.90 (m, lH), 2.20 (m, lH), 2.68 (d, 6H), 3.16 (m, 2H), 3.35 (m, 2H), 3.58 (s, 3H), 6.39 (s, lH), 7.37 (d, lH), 7.77 ~
(d, lH), 7.84 (d, lH) , "
IAi.863 F -CH=C(Br)- p(=o)[oCH(CH3)2]2 1.21 (d, 6H), 1.25 (d, 6H),3.55 (s, 3H), 4.78 (okt, 2H), 6.34 (s, lH), 7.31 (d, lH), 7.62 (d, lH), 7.70 (d, lH) IAj.861 F -CH=C(CN)- p(=O)(OC2Hs)2 1.42 (t, 6H), 3.57 (s, 3H), 4.25 (m, 4H), 6.38 (s, lH), 7.44 (d, lH), 8.26 (d, lH), 8.35 (d, lH) IAk.861 F -CH=C(CH3)- -P(=O)(OC2Hs)2 1.15 and 1.28 (2dt, together 6H), 1.95 and 2.15 (2dd, D
together 3H), 3.52 and 3.56 (2s, together 3H), 3.90 and ~
~ 4.10 (2m, together 4H), 6.31 and 6.36 (2s, together lH), ~
7.02 and 7.43 (2dd, together lH), 7.24, 7.30, 7.38 and 7.62 , (4d, together 2H) '~
Table l~ u F2HCO p Cl , / ~ Y~ 3 = Cl, R4 ~ Eth - p - y2Rl R5 ~2, \=( I Rll = OCHF2, ~
\ y3R2 Rl2 = Cl} D
Cl No. R4 -Eth- -P(=Y')(Y~R')(Y~R~) M.p./1H N M R (~in[ppm])/ MS[m/z]
IBa.861 F -cH2-cH2- _p(=o)(oc2Hs)2 474[M]+,439[M-CI~ ~ ~
IBb.431 Cl -CH2-CH(a)- _p(=O)(OCH3)2 3.11 (dt, lH),3.62 (ddd, lH),3.85(s,3H),3.87 (d, 3H), O
3.92 (d, 3H),4.27 (dt, lH),6.72 (t, lH),7.39(s,lH),7.53 (s,lH) IBb.860 F -CH2-CH(CI)- _p(=O)(OCH3)2 3.12 (ddd, lH),3.64 (ddd, lH),3.85(s,3H),3.87 (d, 3H), 3.91 (d, 3H),4.25 (dt, lH),6.71 (t, lH),7.26 (d,lH), 7.51 (d, lH) IBb.861 F -CH2-CH(CI)- -P(=o)(oc2Hs)2 1.39 (dt, 6H),3.11 (ddd, lH),3.65 (ddd, lH),3.84(s,3H), 4.20-4.30 (m, SH),6.71 (t, lH),7.25 (d, lH),7.52 (d, lH) IBc.860 F -CH2-CH(Br)- _p(=O)(OCH3)2 3.18 (ddd, lH),3.72 (ddd, lH),3.84(s,3H),3.87 (d, 3H), 3.92 (d, 3H),4.21 (dt, lH),6.71 (t, lH),7.25 (d,lH), 7.50 (d, lH) O050/46586 CA 02245659 l998-08-06 6 ~ 6 ~ ~ 66 ~ 6 ~O ~ ~
ac ~ i~+ ~ E~~~
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a~; m ~ m m~ m a~ m m ~m m .
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o ~ ~ ~ ~ ~ ~ ~
ô o ~ ~, X
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~
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~) r~
_ _ ~O, _ U~ O O
O O O O O O
v ~3 ~) m ~ ~ ~ .
~z m m m m m m r~
Table 11 g Cl \N~J\ yl Ic {R3 = Cl, R4~ Eth--p -- y2Rl Rl~ - CH3, \=( ¦ Rl 1 = CF3, D
Cl Y3R2 R12 = Cl} - o !~
No. R4-Eth- -P(=Y')(Y~R')(Y~R~) M.p. / ~H NMR (o in [ppm]) / MS [m/z] ~D
ICa.863 F -cH2-cH2- -P(=o)(ocH(cH3)2)2 504 lM]+, 485 [M-E~l+, 469 [M-CI]+
ICg.861 F -CH=CH- _p(=O)(OC2Hs)2 1.38 (t, 6H), 4.09 (s, 3H), 4.16 (quint, 4H), 6.29 (t, lH), 7.29 (d, lH), 7.78 (d, lH), 7.83 (dd, lH) o ICh.859 F -CH=C(CI)- -P(=O)(OH)2 resin ICh.860 F -CH=C(CI)- -P(=O)(OCH3)2 89-93~C
ICh.861 F -CH=C(CI)- -P(=O)(Oc2Hs)2 62-65~C
ICh.862 F -CH=C(CI)- -P(=O)[O-(n-C3H7)]2 1.01 (t, 6H), 1.78 (sext, 4H), 4.09 (s, 3H), 4.14 (m, 4H), 7.34 (d, lH), 7.87 (d, lH), 8.13 (d, lH) ICh.863 F -CH=C(CI)- -P(=O)[OCH(CH3)2]2 1.39 (d, 6H), 1.43 (d, 6H), 4.08 (s, 3H), 4.79 (okt, 2H), 7.34 (d, lH), 7.88 (d, lH), 8.10 (d, lH) ~ . . _ ~~ o ~ ~ ~ ~o ~ 6 :~
~, 0. ~ .~
~ _ ~ ~, 8 ~~ ~ ~ ~ ~o ~ ~ ~~
Z ~?6 ~? 8 66 6 ~ V ~6 60,, -- ~ ~ ~ ~ ~ ~ ~ ~'~ 6 '-6 ~ o ~ o ~_ o _ ~ ~ ~
C
~- ~ ~ o o oo o z y~
~ o o o oo o o o c~ ~ l l l l l l l v v v vv v v ~
~l v v v v v v v v ~t ' z v v v v v ~ ~ ~
Table 12 - o CF3 yl ID ~R3 = C1, R4~ Eth--P -- y2R1 R5 ~2, \=(~ Rll = R12 = C
Cl y3R2 No.R4 -Eth- -P(=Y')(Y~R')(Y~R;~) M.p. / IH NMR (~ in [ppm]) / MS [m/z]
IDb.860 F -CH2-CH(CI)- -P(=O)(OCH3)2 98-101~C '~
Table 13 O
,~q R4~ Eth--P-- Y2RI y~ - o R13R14 = (CH2)4}
y3R2 D
Cl No. R4 -Eth- _p(=yl)(Y~Rl)(Y~R~) M.p. / lH NMR (~ in [ppm]) / MS [m/z]
IEb.2 H -CH2-CH(CI)- -P(=O)(OcH3)2 1.84 (s, 4H), 2.44 (s, 4H), 3.11 (dt, lH), 3.65 (ddd, lH), - 3.88 (d, 3H), 3.91 (d, 3H), 4.37 (dt, lH), 7.25 (dd, lH), - ~
7.35 (d, lH), 7.46 (d, lH) O
IEg.3 H -CH=CH- -P(=o)(oc2Hs)2 1.37 (t, 6H), 1.84 (s,4H), 2.46 (s, 4H),4.15 (quint, 4H), O
6.19 (t, 1 H), 7.35 (dd, lH), 7.48 (d, lH), 7.64 (d, lH), -7.85 (dd, lH) IEg.56 H -CH=CH- -P(=O)(O-phenyl~Q 124-126~C
IEh.3 H -CH=C(C!)- -P(=O)(OC2Hs)2 114-118~C
IEh.432 Cl -CH=C(CI)- -P(=O)(OC2Hs)2 1.40 (t, 6H), 1.86 (s, 4H), 2.47 (s, 4H), 4.20 (m, 4H), 7.64 (d, lH), 7.85 (s, lH), 7.86 (s, lH) IEb.860 F -CH2-CH(CI)- -P(=O)(OCH3)2 1.86 (s, 4H), 2.47 (s, 4H), 3.12 (dt, lH), 3.62 (ddd, lH), 3.85 (d, 3H), 3.90 (d, 3H), 4.20 (dt, lH), 7.25 (d, lH), 7.32 (d, lH) o ~-- ~ ~ ~ ~
~--@ ~ ~ ? ~
rC ~D ~? ~ ~C o r t~
~ O O
~_ '~ ~ O ~ O
_~ _ _ _ _ ~) m ~ ~OD
00 ~ 00 00 Z ~ ~ $ ~
Table 14 ~
H3C~f H3C ~/
6~N yl IF {R3 = Cl, O 1I R5 = <p3, R4~/ \~ Eth--P --Y2Rl y4 0 \~:( ¦ R13 = R14 = CH3}
y3R2 D
Cl No. R4 -Eth- -P(=Yl)(Y~R~)(YJR~) M.p. / IH NMR (~ in [ppm]) / MS [m/z]
IFg.3 H -CH=CH- -p(=o)(oc~Hs)2 736(dd,IH),749(d,IH);7.64(d,iH),7.g4(dd lH) ~
1Fh.3 H -CH=C(CI)- -P(=O)(Oc2Hs)2 124-126~C x .
Table 15 0 o O
I ~n N yl R~ th - P - YZRI Rs - ~4, Cl y3R2 Rl7 = Cl} D
No.R4 -Eth- -P(=Y')(Y'RI)(Y~R~) M.p./ 'H N M R (oin[ppm])/ MS[m/z] ~o IGb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 1.85 (m, 4H),2.52 (t, 2H),2.72 (t, 2H),3.15 (ddd, lH), 3.70 (ddd, lH),3.92 (d, 3H),3.95 (d, 3H),4.30 (dt, lH), 7.45(s,2H),7.55(s,lH) ~
IGb.3 H -CH2-CH(CI)- -P(=O)(Oc2Hs)2 1.37 (m, 6H),1.82 (m, 4H),2.52(t,2H),2.72(t,2H),3.13 ~
(ddd, lH),3.70 (ddd, lH),4.20-4.35(m,SH),7.47 (s,2H),7.54(s,lH) IGb.860 F-CH2-CH(CI)- -P(=O)(OCH3)2 1.82 (m, 4H),2.51(t,2H),2.71 (t, 2H),3.11 (ddd, lH), 3.63 (ddd, lH),3.88 (d, 3H),3.92 (d, 3H),4.25 (dt, lH), 7.32 (d, lH),7.44 (d, lH) - Q r~ ~
Table 16 o F2HC Cl N
H3C~ yl . .
N~ IH {R3 z Cl /~ 1I R5 a (p5 ~
R4~/ \~ Eth--P -- Y2Rl R18 = Cl, \=( ¦ R19 = CHF2, Cl y3R2 R20 = CH3 } D
No. R4 -Eth- -P(=Yl)(y'Rl)(y~R~) M.p. / lH NMR (o in [ppm]) / MS [m/z] ~0 IHb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 2.62 (s, 3H), 3.15 (ddd, lH), 3.70 (ddd, lH), 3.88 (d, 3H), ~o 3.94 (d, 3H), 4.34 (dt, lH), 7.15 (t, lH), 7.M (d, lH), 7.79 (dd, lH), 7.87 (d, lH) ~
Table 17 o o ~NJ~ N yl a~
R4~ Eth--P -- Y2RI IR ~R3 ~ Cl \~ R23R24 - (CH2 ) 4}
Cl y3R2 D
No. R4 -Eth- -P(=Y~)(Y~RI)(Y~R~) M.p. / 'H NMR (~ in [ppm]) / MS [m/z] n IKh.861 F -CH=C(CI)- -P(=O)(OC2Hs)2 1.41 (t, 6H), 1.96 (m, 4H), 2.79 (t, 2H), 3.72 (t, 2H), 4.23 (q, 4H), 7.36 (d, lH), 7.84 (d, lH), 8.15 (d, lH) cl~
Table 18 0 CF3 ~
S~,N~ yl , N 11 IL {R3 = Cl, R4~ Eth--P --y2RlR5 ~20, 51 = CF3, ~
Cl y3R2 R52 = H} D
. .~
No. R4 -Eth- -P(=YI)(Y~R')(Y~R~) M.p. / IH NMR (o in [ppml) / MS [m/z] ~0 ILh.861 F -CH=C(CI)-! -P(=O)(O~zHs)2 1.40 (~, 6H), 3.57 (s, 3H), 4.~ (m, 4H), 6.58 (s, lH), 7.24 (d, lH), 7.69 (d, lH), 7.86 (d, lH) r ~ . .
Table 19 g O ' o ~N
~N~, S
~ Il yl r~
N IM {R3 = Cl, ~ ¦¦ .R5 = ~21, R4~/ \~ Eth--P -- Y2R1 z3 = z4 = N, \=~ R53R54 = ( CH2 ) 4 }
C1 y3~2 No. R4 -Eth- -P(=Y')(Y~R')(YJR~) M.p. / lH NMR (o in [ppm]) / MS ~m/z] ~O
IMh.861 F -CH=C(Cl)- -P(=O)(OC2Hs)2 1.41 (t, 6H), 1.80-2.00 (m,4H), 3.75 (t, 2H), 3.84 (t,2H), o 4.22 (m, 4H), 7.24 (d,lH), 7.57 (d,lH), 7.84 (d, IH) '~
r~
Table 2 0 0 H3C >~N
H3C N I yl N IN {R3 = Cl, ~ 1I R5 = ~22, R4~/ \~ Eth--P-- Y2Rl R55R56 =
CH2 -C ( CH3 ) 2 -CH2 - }
Cl y3R2 D
~, No. R4 -Eth- _p(=yl)(Y2R~)(Y3R~) M.p. / lH NMR (~ in [ppm]) / MS [m/z] N
INh.861 F -CH=C(CI)- -P(=O)(OC2HS)2 117-120~C . o x x - , OOSO/46586 CA 0224~659 1998-08-06 Use examples (herbicidal activity) 5 The herbicidal activity of the substituted aromatic phosphonic acid derivatives I was demonstrated by the greenhouse experiments which follow:
The culture cont~in~rs used were plastic flower pots contA;ning 10 loamy sand with approximately 3.0 ~ of humus as the substrate.
The seeds of the test plants were sown separately for each species.
For pre .~ -rgence treatment, the active ingredients, which had 15 been suspended or emulsified in water, were applied by means of finely distributing nozzles directly after sowing. The cont~;n~rs ~~ were irrigated gently to promote ger~;n~tion and growth and subsequently covered with translucent plastic hoods until the plants had rooted. This cover causes uniform g~rmin~tion of the Z0 test plants unless this was adversely affected by the active in-gredients.
For post-emergence treatment, the test plants were first grown to a plant height of 3 to lS cm, ~ep~n~ing on the plant habit, and 25 only then treated with the active ingredients which had been sus-pended or emulsified in water. The test plants were either sown directly and grown in the same cont~iners~ or they were first grown separately as seedlings and transplanted into the test con-tainers a few days prior to treatment. The rate of application 30 for the post-emergence treatment was 15.6, 7.8, 1.9 or 0.9 g of a.s. (active substance)/ha.
.., ~~ Depending on the species, the plants were kept at from 10 to 25~C
35 or from 20 to 35~C. The test period exten~e~ over 2 to 4 weeks.
During this time, the plants were ten~e~, and their response to the individual treatments was evaluated.
Evaluation was effected using a scale of from 0 to 100. 100 means 40 no emergence of the plants or complete destruction of at least the aerial parts, and 0 means no damage or normal course of growth.
The plants used in the greenhouse experiments belonged to the 45 following species:
-Scit~ntific name Common name Oryza sativa rice Abutilon theophrasti velvet leaf S ~m~ redroot pigweed retroflexus Chenopodium album lambs~lucu~
(goosefoot) 10 Galium aparine catcL~icd l~ed~ w Ipomoea subspecies morning glory Polygonum persicaria lady's thumb Solanum nigrum black ni~ht!ih~
15 Veronica ~ubs~ccies speedwell - At rates of application of 1.9 and 0.9 g of a.s./ha, compound No.
IBg.861 applied post-emergence showed a selective herbicidal ac-tivity against Abutilon theophrasti, Amaranthus retroflexus and 20 Solanum nigrum in the crop rice, which was only damaged to a minor extent.
Compounds No. IBh.861 and No. IAh.861, applied post-emergence at the same rates of application, showed a very good activity 25 against Abutilon theophrasti, Amaranthus retroflexus and Solanum nigrum.
At rates of application of 15.6 and 7.8 g of a.S./ha, compounds No. IBg.861, IBh.861 and IAh.861 control Amaranthus retroflexus, 30 Chenopodium album, Galium aparine and Solanum nigrum better than the co~r~ison o~...~ound A, which is known from ASC Symp. Ser. 584 (1995), go Cl ~ Cl Cl ~
CH2 - CH p ~C2Hs (A) ~N~N
F2HC ~C2Hs - 0050/46586 CA 022456~9 1998-08-06 Use examples (desiccant/defoliant activity) The test plants used were young cotton plants with 4 leaves (without cotyledons) which had been grown under greenhouse condi-5 tions (relative humidity 50 to 70 %; day/night t~mp~rature 27/20~C).
The young cotton plants were subjected to foliar treatment to 10 drip point with aqueous preparations of the active ingredients (with an addition of 0.15 % by weight of the fatty alcohol al-koxylate Plurafac LF~ 7001, based on the spray mixture). The amount of water applied was 1000 l/ha (converted). After 13 days, the number of shed leaves and the degree of defoliation in % were det~r~; ne~ .
No leaves were shed in the untreated control plants.
1) a low-foam, non-ionic surfactant from sASF AG
lH NMR (270 MHz; in CDCl3): ~ [ppm] = 2.63 (s,3H), 7.16 (t,lH), 7.59 (d,lH), 8.09 (dd,lH), 8.47 (d,2H).
- ~ 0050/46586 CA 0224~6~9 l998-08-06 .
Precursor 6.5 2-Chloro-5-(5-chloro-1-difluoromethyl-2-methyl-lH-imida- -zol-4-yl)aniline 7 g (22 mmol) of 5-chloro-4-(4-chloro-3-nitrophenyl)-1-difluo-romethyl-2-methyl-lH-imidazole were dissolved in 200 ml of meth-anol with heating. This solution was added dropwise to a suspen-sion of 3.6 g (65 mmol) of iron powder in 150 ml of glacial acetic acid, stirred at reflux temperature. After 3 hours, the reaction mixture was poured into 500 ml of water. A further 500 ml of ethyl acetate were added to the mixture, whereupon the iron residues were filtered off. The aqueous phase was separated off and mixed with another 500 ml of ethyl acetate. The combined or-ganic phases were washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate and finally con-centrated. To 1~ ~ve the re-~;n;ng acetic acid, the crude product was treated with 100 ml of toluene, whereupon the mixture was again concentrated to dryness. Yield: 5.7 g.
20 lH NMR (270 MHz; in CDCl3): ~ [ppm] = 2.60 (s,3H), 4.13 (s,2H), 7.12 (t,lH), 7.15-7.35 (m,3H).
Example 7 Dimethyl l-bromo-2-t2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-Z5 1,3-dioxo-2H-isoindol-2-yl)phenyl]ethylphosphonate (No. IEc.860) Following the procedure described in Example 5 and using 21.2 g (0.16 mol) of dimethyl vinylphosphonate, 1.8 g (8 mmol) of copper(II) bromide, 1.1 g (11 mmol) of tert-butyl nitrite and 30 2.0 g (6.8 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)An;l;ne, 0.7 g of the above product of value is obtA; n~ .
35 Example 8 Dimethyl l-chloro-2-(2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)ethylphosphonate (No. IEb.860) Following the procedure described in Example 5 and using 21.2 g 40 (0.16 mol) of dimethyl vinylphosphonate, 1.1 g (8 mmol) of copper( II ) chloride, 1.1 g (11 mmol) of tert-butyl nitrite and 2.0 g (6.8 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)aniline, 1.0 g of the above product of value is obt~; ne~ .
- 0050/46586 CA 0224~6~9 1998-08-06 Example 9 Dimethyl l--chloro--2--[2--chloro--5--(3--chloro--4,5,6,7-tetrahydro--2H--indazol-2--yl)phenyl]ethylphosphonate(No. IGb.2) 5 Following the procedure described in Example 5 and using 42.4 g (0.31 mol) of dimethyl vinylphosphonate, 2.2 g (16 mmol) of copper(II) chloride, 2.2 g (22 mmol) of tert-butyl nitrite and 4.0 g (14 mmol) of 2--chloro--5--(3--chloro--4,5,6,7--tetrahydro--2H-indazol--2--yl)Anil;ne~ 0.8 g of the above product of value is 10 obtA;ne~.
Example 10 Dimethyl l--chloro--2--t2,4-dichloro--5-(4--chloro-5-difluoromethoxy--15 1--methyl--lH--pyrazol--3--yl)phenyl]ethylphosphonate(No. IBb.431) Following the procedure described in Example 5 and using 32.6 g (0.24 mol) of dimethyl vinylphosphonate, 3.6 g (26 mmol) of copper(II) chloride, 2.6 g (25 mmol) of tert-butyl nitrite and 20 13.6 g (24 mmol) of 2,4-dichloro-5-(4-chloro-5-difluoromethoxy-l--methyl-lH--pyrazol--3--yl)An;l;ne~ 3.6 g of the above product of value are obtAine~l.
Example 11 25 Dimethyl 1-chloro--2--(2-chloro-5--(1-methyl--6--trifluoromethyl--2,4(1H,3H)-pyrimi~inerlion--3--yl)phenyl)ethylphosphonate (No. IAb.2) Following the procedure described in Example 5 and using 17.9 g 30 (0.13 mol) of dimethyl vinylphosphonate, 0.9 g (7 mmol) of copper(II) chloride, 0.65 g (6.5 mmol) of tert-butyl nitrite and C' 2.0 g (6.3 mmol) of 2--chloro-5--(1--methyl--6--trifluoromethyl--- 2,4(1H,3H)--pyrimi~lineAion--3--yl)Anilin~ 1.0 g of the above product of value is obtAine~l.
Example 12 Dimethyl l-chloro--2--(2--chloro--4--fluoro--5--tl--methyl--4,5--di--(trifluoromethyl)--lH-pyrazol--3--yl)phenyl)ethylphosphonate 40 (No. IDb.860) Following the procedure described in Example 5 and using 13.1 g (96 mmol) of dimethyl vinylphosphonate, 0.7 g (5 mmol) of copper(II) chloride, 0.5 g (5 mmol) of tert-butyl nitrite and 45 1.2 g (4.6 mmol) of 2--chloro-4--fluoro--5--(1--methyl--4,5--di--- (trifluoromethyl)--lH--pyrazol--3--yl)aniline,0.6 g of the above product of value is obtAine~l.
-~ 0050/46586 CA 0224~6~9 1998-08-06 , Example 13 Diethyl l-chloro-2-[2-chloro-5-(4-chloro-S-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyllethylphosphonate (No. IBb.861) Following the procedure described in Ex_mple 5 and using 12.5 g (85 mmol) of diethyl vinylphosphonate, 0.7 g (5 mmol) of copper(II) chloride, 0.5 g (5 mmol) of tert-butyl nitrite and 1.5 g (4.6 mmol) of 2-chloro-4-fluoro-5-(4-chloro-5-difluoro-10 methoxy-1-methyl-lH-pyrazol-3-yl)An;lin~, 0.6 g of the above product of value is obtA i neA .
Example 14 15 Diethyl l-bromo-2-(2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyl)ethylphosphonate (No. IBc.861) Following the procedure described in Example 5 and using 12.5 g 20 (85 mmol) of diethyl vinylphosphonate, 1.1 g (5 mmol) of copper(II) bromide, 0.5 g (5 mmol) of tert-butyl nitrite and 1.5 g (4.6 mmol) of 2-chloro-4-fluoro-5-(4-chloro-5-difluoro-methoxy-l-methyl-lH-pyrazol-3-yl)Aniline~ 0.8 g of the above product of value is obtA;ne~.
Example 15 Diethyl 2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate (No. ICg.861) 30 Following the procedure described in Example 1 and using 0.45 g 1.5 mmol) of tetraethyl methAneAiphosphonate, 36 mg (1.5 mmol) of sodium hydride and 0.5 g (1.5 mmol) of 2-chloro-5-(4-chloro-l-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorobenz~ hyde, 0.4 g of the above product of value is obtA i neA .
Example 16 Diethyl 2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.3) Following the procedure described in Example 1 and using 0.5 g (1.7 mmol) of tetraethyl methaneAiphosphonate, 40 mg (1.7 mmol) of sodium hydride and 0.5 g (1.7 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 45 0.2 g of the above product of value is obt~; neA .
~ 0050/46586 CA 0224~6~9 1998-08-06 .
Example 17 Diethyl 2-(2-chloro-4-fluoro-S-(1,3,4,5,6,7-hexahydro-1,3-dioxo- -2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.861) 5 Following the procedure described in Example 1 and using 0.5 g (1.7 mmol) of tetraethyl me~h~ne~;phosphonate, 39 mg (1.7 mmol) of sodium hydride and 0.5 g (1.6 mmol) of 2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydlo 1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 0.4 g of the above product of value is obt~;ne~.
G
Example 18 Diethyl 2-t2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)-phenyl]vinylphosphonate (No. IFg.3) Following the procedure described in Example 1 and using 0.55 g (1.9 mmol) of tetraethyl me~h~ne~;rhosphonate, 45 mg (1.9 mmol) of sodium hydride and 0.5 g (1.9 mmol) of 2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)h~n~ ehyde~ 0.5 g of 20 the above product of value is obtAine~. M.p.: 93-94~C.
Example 19 Diethyl 2-(2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimi~;ne~;on-3-yl)phenyl)vinylphosphonate (No. IAg.3) Following the procedure described in Example 1 and using 0.73 g (2.5 mmol) of tetraethyl methAne~;phosphonate, 57 mg (2.4 mmol) of sodium hydride and 0.5 g (1.5 mmol) of 2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrimidinedion-3-yl)benzaldehyde, 30 0.4 g of the above product of value is obt~ine~.
Example 20 Diethyl 2-(2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-35 pyrimi~;ne~;on-3-yl)vinylphosphonate (No. IAg.432) Following the procedure described in Example 1 and using 0.7 g (2.3 mmol) of tetraethyl meth~ne~;rhosphonate, 52 mg (2.3 mmol) of sodium hydride and 0.5 g (1.4 mmol) of 2,4-dichloro-5-40 (1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimi~;ne~;on-3-yl)-benzaldehyde, 0.5 g of the above product of value is obtained.
.
OOSO/46586 CA 0224~6~9 1998-08-06 Precursor 20.1 2,4-Dichloro-5-isocyanatobenzaldehyde (O-ethyl)oxime 65.3 g (0.28 mol) of 5-amino-2,4-dichlorobenzaldehyde (O-ethyl)-5 oxime (obt~in~hle by the process given for precursors 28.1-28.3) and 60.9 g (0.31 mol) of diphosgene were reacted in the m~nner described for precursor 3.1. Yield: 72.9 g.
Precursor 20.2 2,4-Dichloro-5-(6-trifluoromethyl-2,4(1H,3H)-pyrim;~ine~ion-3-yl)benzaldehyde (O-ethyl)oxime 9.2 g (0.31 mol) of sodium hydride, 51.3 g (0.28 mol) of ethyl 15 3-amino-4,4,4-trifluorocrotonate and 72.6 g (0.28 mol) of 2,4-dichloro-5-isocyanatohen7-aldehyde (O-ethyl)oxime were reacted f in the m~nn~r described for precursor 3.2. Yield: 72.0 g;
m.p.: 205-209~C.
20 Precursor 20.3 2,4-Dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyrim;~i n~ -dion-3-yl)benzaldehyde (O-ethyl)oxime 69.3 g (0.175 mol) of 2,4-dichloro-5-(6-trifluoromethyl-25 2,4(lH,3H)-pyri i~ine~ion-3-yl)~en 7.~1 dehyde (O-ethyl)oxime, 26.6 g (0.19 mol) of potassium carbonate and 27.3 g (0.19 mol) of methyl iodide were reacted in the ~-nner described for precursor 3.3. Yield: 69.0 g; m.p.: 140-143~C.
Precursor 20.4 2,4-Dichloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimi~in~-dion-3-yl)benzaldehyde 35 61.5 g (0.15 mol) of 2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyr;mi~in~ion-3-yl)benzaldehyde (O-ethyl)oxime were reacted in the m-nner described for precursor 3.4. Yield: 50.0 g;
m.p.: 117-120~C.
40 Example 21 Diphenyl 2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEg.56) 2.6 g (5.2 mmol) of diphenyl (triphenylphosphorany~i~ene)methane-45 phosphonate and 1 g (3.4 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexa-hydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde were dissolved in 100 ml of toluene, whereupon the mixture was refluxed for - 0050/46586 CA 0224~6~9 1998-08-06 .
4 hours. The reaction mixture was subsequently concentrated. The crude product obtained as residue was purified by means of silica gel chromatography (eluent: h~n~/ethyl acetate = 2:1) followed by crystallization from he~Ane/ethyl acetate. Yield: 0.8 g.
s Example 22 Diethyl l-chloro-2-(2-chloro-S-(4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate (No. ICh.861) Following the procedure described in Example 2 and using 37.3 g (0.15 mol) of diethyl trichloromethanephosphonate, 42 ml (67 mmol) of a 1.6-molar butyllithium solution and 10 g (29 mmol) lS of 2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorobenzaldehyde, 12.8 g of the above product of value are obtained.
Example 23 20 Diethy~ 1-chloro-2-(2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEh.3) Following the procedure described in Example 2 and using 4.4 g (17 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) 25 of a 1.6-molar butyllithium solution and 1 g (3.5 mmol) of 2-chloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)-benzaldehyde, 0.6 g of the above product of value is obtAine~.
Example 24 30 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl)vinylphosphonate (No. IEh.861) Following the procedure described in Example 2 and using 4.1 g 35 (16 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (3.2 mmol) of 2-chloro-4-fluoro-5(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)benzaldehyde, 0.6 g of the above product of value is obtained.
- 0050/46586 CA 0224~6~9 1998-08-06 .
~ 170 Example 25 Diethyl l-chloro-2-(2-chloro-5-(3,4-dimethyl-lH ~yllole-2,5-dion- .
l-yl)-phenyl)vinylphosphonate (No. IFh.3) 5 Following the procedure described in Example 2 and using 4.8 g (19 mmol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (3.8 mmol) of 2-chloro-5-(3,4-dimethyl-lH-pyrrole-2,5-dion-1-yl)benzaldehyde, 0.4 g of the above product of value is obt~; n~
Example 26 Diethyl 1-chloro-2-t2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyr; mi ~; ne~; on-3-yl)phenyl]vinylphosphonate Following the procedure described in Example 2 and using 4 g - (16 mmol) of diethyl trichlorometh~nephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 0.7 g (2.8 mmol) of 20 2-chloro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyri~;~;n~;on- .
3-yl)benzaldehyde, 0.5 g of the above product of value is obt~ine~.
Example 27 25 Diethyl l-chloro-2-t2,4-dichloro-5-(1-methyl-6-trifluoromethyl-2,4(lH,3H)-pyr; m; ~; neA; o~-3-yl)phenyl]vinylphosphonate (No. IAh.432) Following the procedure described in Example 2 and using 4 g 30 (16 m.mol) of diethyl trichloromethanephosphonate, 5 ml (8 mmol) of a 1.6-molar butyllithium solution and 1 g (2.7 mmol) of L 2,4-dichloro-5-(l-methyl-6-trifluoromethyl-2,4(1H,3H)-pyr~ ;ne ~- dion-3-yl)benzaldehyde, 0.3 g of the above product of value is obt~;ne~.
Example 28 Diethyl l-chloro-2-t2,4-dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl)phenyl]vinylphosphonate (No. IEh.432) Following the procedure described in Example 2 and using 1.5 g (6 mmol) of diethyl tr;chlo~omethanephosphonate, 1.8 ml (2.9 mmol) of a 1.8-molar butyllithium solution and 0.3 g (o.9 mmol) of 2,4-dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-45 2H-isoindol-2-yl)benzaldehyde, 0.3 g of the above product of value is obt~; ne~ .
- 0050/46586 CA 0224~6~9 1998-08-06 , Precursor 28.1 2,4-Dichloro-5-nitrobenzaldehyde A solution of 125 g of nitric acid in 153 g of sulfuric acid 5 which had been prepared with ice-cooling at (-5)~C was added dropwise to a solution of 262.5 g (1.5 mol) of 2,4-dichlorobenzaldehyde in 560 ml of sulfuric acid. After the reaction mixture had been stirred for 2 hours at 10~C, it was poured onto 4 kg of ice. The resulting solids were subsequently 10 separated off, washed with water and dissolved in 2 1 of dichloromethane. The resulting solution was washed with saturated aqueous sodium hydrogen carbonate solution, then dried over magnesium sulfate and finally concentrated. Yield: 329.5 g;
m.p.: 61-63~C.
_ Precursor 28.2 2,4-Dichloro-5 - nitroh~n 7 A ldehyde (O-methyl)oxime 20 93.1 g (0.223 mol) of methoxyamine hydrochloride (20% strength by weight solution in water) were treated with 100 ml of water and 18.7 g (0.223 mol) of sodium hydrogen carbonate. A solution of 44 g (0.2 mol) of 2,4-dichlorobenzaldehyde in 200 ml of toluene were added dropwise to tnis mixture. l~ne mixture was subsequently 25 heated for 5 hours at 50~C. The organic phase was then separated off. After washing with water and saturated aqueous sodium chloride solution, the resulting crude-product solution was dried over magnesium sulfate and finally concentrated. Yield: 39.2 g;
m.p.: 77-79~C.
Precursor 28.3 5-Amino-2,4-dichlorobenzaldehyde (O-methyl)oxime 16.8 g (0.3 mol) of iron powder were dissolved in 130 ml of methanol and 100 ml of acetic acid. A solution of 24.9 g (0.1 mol) of 2,4-dichloro-5-nitrobenzaldehyde (O-methyl)oxime in 100 ml of acetic acid and 100 ml of methanol was added dropwise to this solution at 70~C. The reaction mixture was then heated for 1 hour at 75-80~C, whereupon it was poured onto 3 kg of ice. The 40 product of value was subsequently extracted with 2 1 of dichloromethane. The organic phase was dried over magnesium sulfate and finally concentrated. The crude product was purified by stirring with a small amount of pentane. Filtration gave 18.5 g of product of value. M.p.: 129-132~C.
- ~ 0050/46586 CA 0224~6~9 l998-08-06 Precursor 28.4 2,4-Dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl) benzaldehyde (O-methyl)oxime 5 18 g (82 mmol) of 5-amino-2,4-dichlorobenzaldehyde (o-methyl)oxime were added to a solution of 12.5 g (82 mmol) of 3,4,5,6-tetrah~dLophthalic anhydride in 300 ml of acetic acid, whereupon the mixture was stirred for 15 hours at reflux temperature. The reaction mixture was subsequently poured into 10 1 l of water. The product was then extracted with 300 ml of methyl tert-butyl ether. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate and finally concentrated. The residue was purified by means of silica gel chromatography (eluent: h~ne/ethyl acetate 15 = 4:1). Yield: 20.9 g; m.p.: 122-124~C.
Precursor 28.5 2,4-Dichloro-5-(1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl) 20 benzaldehyde 9 ml of a 37% strength by weight aqueous formaldehyde solution and 9 ml of concentrated hydrochloric acid were added to a solution of 10.6 g (30 mmol) of 2,4-dichloro-25 5-(1,3,4,5,6,7-hexah~dlo 1,3-dioxo-2H-isoindol-2-yl)ben~ ehyde (O-methyl)oxime in 45 ml of acetic acid. The mixture was subsequently heated for 1 hour at 50-60~C, whereupon the reaction mixture was poured into 300 ml of ice-water. The product was extracted from the resulting mixture using 200 ml of 30 dichloromethane. The extract was dried over magnesium sulfate and then concentrated. The ~esidue was purified by means of silica gel chromatography (eluent: heY~ne/ethyl acetate = 4:1). Yield:
5.2 g; 1H NMR (270 MHz; in CDCl3): atppm] s 1.85 (s, 4H), 2.45 (s, 4H), 7.67 (s, lH), 7.81 (s, lH), 10.40 (s, lH).
Example 29 Diisopropyl 2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)ethylphosphonate (No. ICa.863) 40 A suspension of 6 g (11 mmol) of diisopropyl 1-chloro-2-(2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonate, 1.1 g (13 mmol) of sodium acetate and 50 mg of 5% palladium on active charcoal in 100 ml of ethanol was treated with 5 bar of hydrogen. After the mixture had 45 been stirred for one day, the catalyst was Lc..~ved by filtration.
The filtrate was concentrated. 100 ml of water and 100 ml of ethyl acetate were added to the resulting residue. The organic - ~ 0050/46586 CA 0224~6~9 1998-08-06 .
173 _ phase was separated off, dried over magnesium sulfate and finally concentrated. Silica gel chromatography of the residue (eluent:
h~n~/ethyl acetate = 3:1) first gave 0.2 g of the product of value and then 1.5 g of diisopropyl 5 2-t5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl]ethyl-phosphonate.
Example 30 l-Chloro-2-(2-chloro-5-(4-chloro- 1-methyl-5-trifluoromethyl-10 lH-pyrazol-3-yl)-4-fluorophenyl)vinylphosphonic acid (No. ICh.859) A solution of 1 g (2 mmol) of diethyl 1-chloro-2-t2-chloro-15 5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluoro-phenyl]vinylphosphonate~ 0.97 g (5.9 mmol) of potassium iodide and 0.6 g (5.9 mmol) of chlorotrimethylsilane in 20 ml of acetonitrile was heated for 3 hours at 50-60~C. The mixture was subsequently concentrated. The residue was treated with 50 ml of 20 water and 50 ml of ethyl acetate. After the organic phase had been separated off and dried over magnesium sulfate, the mixture was concentrated. Yield: 0.7 g.
Example 31 25 1-Chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid (No. IBh.859~
Following the procedure described in Example 30 and using 11.4 g 30 (22.6 mmol) of diethyl 1-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl-phosphonate, 11.3 g (68 mmol) of potassium iodide and 7.8 g (67 mmol) of chlorotrimethylsilane, 9 g of the above product of value are obt~; n~A .
Example 32 l-Chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-(lH,3H)pyr; m; A; neA; on-3-yl)phenyl]vinylphosphonic acid (No. IAh.859 Eollowing the procedure described in Example 30 and using 5 g (9.6 mmol) of diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr; m; ~; neA;on-3-yl)phenyl]vinyl-45 phosphonate, 4.8 g (29 mmol) of potassium iodide and 3.1 g(29 mmol) of chlorotrimethylsilane, 4.5 g of the above product of value are obtained.
- ~ 0050146586 CA 022456S9 1998-08-06 .
Example 33 Dimethyl l-chloro-2-[2-chloro-5-(4-chloro-1-methyl-5-trifluoro-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (~o.
ICh.860) 0.7 g (5.5 mmol) of oxalyl chloride and one drop of dimethyl-formAm;~e were added to a solution of O.7 g (1.5 mmol) of l-chloro-2-l2-chloro-5-(4-chloro-1-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid in 30 ml of lO dichloromethane. After the evolution of gas had ceased, a solution of 2.3 g (15 mmol) of methanol and 0.6 g (8 mmol) of pyridine in 50 ml of dichloromethane was added dropwise to the resulting mixture. The reaction mixture was stirred for a further 2 hours and subsequently concentrated. The residue was treated 15 with 50 ml of water and 50 ml of ethyl acetate. The organic phase was dried over magnesium sulfate and then concentrated. The crude product was purified by means of siliga gel chromatography (eluent: h~YAne/ethyl acetate = 3:1). Yield: 0.25 g.
Example 34 2~ Chloro-2-[2-chloro-5-(4-chloro-l-methyl-5-trifluoromethyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl)-2,1,3-phosph~;ox~n-2-one (No. ICh.1154) Following the procedure described in Example 33 and using l g (2.2 mmol) of l-chloro-2-t2-chloro-5-(4-chloro-1-methyl-S-tri-fluoromethyl--lH--pyrazol--3--yl)--4--fluorophenyl]vinylphosphoni~
acid, 0.7 g (5.5 mmol) of oxalyl chloride, 1.5 g (20 mmol) of 30 1,3-propAne~;ol and 0.8 g (10 mmol) of pyridine, 0.6 g of the above product of value is obt~ne~.
~_ Example 35 Dimethyl l-chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-35 1-methyl-1~-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No. I8h.860) Following the procedure described in Example 33 and using 0.7 g (1.5 mmol) of 1-chloro-2-l2-chloro-5-(4-chloro-5-difluoromethoxy-40 1-methyl-lH-pyrazol-3-yl)-4-fluorophenyllvinylphosphonic acid, 0.7 g (5.5 mmol) of oxalyl chloride, 0.45 g (14 mmol) of methanol and 0.56 g (7.2 mmol) of pyridine, 0.3 g of the above product of value is obt~;ne~.
- 0050/46586 CA 0224~6~9 1998-08-06 .
175 _ Example 36 2-(1-Chloro-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH--pyrazol-3--yl)--4-fluorophenyl]vinyl)-2,1,3-phosphA~l;oxan--2--one (No. IBh.1154) Following the procedure described in Example 33 and using 0.7 g (1.5 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-flUorophenyl]VinylphosphoniC acid, 0.7 g (5.5 mmol) of oxalyl chloride, 1 g (14 mmol) of 10 1,3-propanediol and 0.56 g (7.2 mmol) of pyridine, 0.3 g of the above product of value is obtA;ne~.
Example 37 S,S-Diethyl 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyldithiophosphonate f (No. IBh.1271) Following the procedure described in Example 33 and using 0.8 g 20 (1.8 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonic acid, 0.5 g (3.9 mmol) of oxalyl chloride, 1.0 g (18 mmol) of ethylmercaptan and 0.7 g (8.8 mmol) of pyridine, 0.5 g of the above product of value is obtA;ne~.
Example 38 2-(1-Chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinyl)-1,3-dimethylperhydro-2,1,3-phosphA~iA7in-2-one (No. IBh.1256) Following the procedure described in Example 33 and using 0.8 g ~1.8 mmol) of 1-chloro-2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonic acid, 0.5 g (3.9 mmol) of oxalylchloride, 1.8 g (18 mmol) of 35 N,N'-dimethyl-1,3-~;; ;nopropane and 0.7 g (8.8 mmol) of pyridine, 0.34 g of the above product of value is obtained.
Example 39 40 Dimethyl l-Chloro-2-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl--2,4-(lH,3H)pyr;m;~l;nadion--3-yl)phenyl]vinylphosphonate (No. IAh.860) Following the procedure described in Example 33 and using 0.9 g 45 (1.9 mmol) of 1-chloro-2-[2-chloro-4-fluoro-5-(1-methyl-6-tri-fluoromethyl-2,4(1H,3H)pyrimi~;ne~;on-3-yl)phenyl]vinylphosphonic acid, 0.7 g (5.5 mmol) of oxalyl chloride, 0.6 g (19 mmol) of - 0050/46586 CA 0224~6~9 1998-08-06 methanol and 0.75 g (9.5 mmol) of pyridine, 0.2 g of the above product of value i5 obtained.
Example 40 5 Diisopropyl l-chloro-2-t2-chloro-4-fluoro-5-(1-methyl-6-tri-fluoromethyl--2,4--(lH,3H)pyr;m;~;ne~;on--3--yl)phenyl]vinyl--phosphonate (No. IAh.863) .
10 0 4 g (15 mmol) of sodium hydride was added to a solution of 5.8 g (15 mmol) of tetraisopropyl chloromethane~;phosphonate in 100 ml of tetrahydrofuran. After the mixture had been stirred for 30 minutes, 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr;m;~;n~A;on-3-yl)benzaldehyde were 15 added. The mixture was subsequently stirred for 1 hour. The reaction mixture was then treated with 50 ml of water and 50 ml of ethyl acetate. The organic phase was separated off, dried over magnesium sulfate and finally concentrated. The crude product obtained was purified by means of MPLC on silica gel (eluent:
20 he~Ane/ethyl acetate = 2:1). Yield: 1.1 g.
Example 41 Diisopropyl l-bromo-2-12-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl--2,4--(lH~3H)pyr;m;c~;ne~l;on--3--yl)phenyl]Vinylphosphonate 25 (No- IAi.863) Following the procedure described in Example 40 and using 6.5 g (15 mmol) of tetraiso~Lo~yl b~ thAne~;rhosphonate, 0.4 g (15 mmol) of sodium hydride and 3.2 g (9 mmol) of 2-chloro-30 4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyr;m;~;ne~;on-3-yl)benzaldehyde, 2.6 g of the above product of value are obtained.
Example 42 35 Diethyl 2-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4(1H,3H)pyrimi~; ne~; on-3-yl)phenyl]-1-cyanovinylphosphonate (No. IAj.861) 40 A solution of 1.6 g (9 mmol) of diethyl cyanomethanephosphonate, 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoro-methyl-2,4(lH,3H)pyr; m; ~; nedion-3-yl)benzaldehyder 0.6 ml of acetic acid and 0.18 ml of piperidine in 60 ml of toluene was refluxed for 6 hours, whereupon the mixture was concentrated. The 45 crude product obtA;n~ was purified by silica gel chromatography (eluent: hexane/ethyl acetate ~ 1:1). Yield: 1.8 g.
-~ 0050/46586 CA 0224~6~9 1998-08-06 .. . .
Example 43 Diethyl 1-~2-chloro-4-fluoro-S-(l-methyl-6-trifluoromethyl-2,4(1H,3H)pyrim;~ine~;on-3-yl)phenyl]prop-l-en-2-ylphosphonate (No. IAk.861) A solution of 10 ml (20 mmol) of a 2-molar solution of lithium diisopropylamide in 50 ml of tetrahydrofuran was cooled to (-60)~C
and at this temperature treated with 1.5 g (9 mmol) of diethyl ethanephosphonate, whereupon the mixture was stirred for 10 15 minutes. The mixture was subsequently cooled to (-70)~C, and 1 g (9.5 mmol) of chlorotrimethylsilane was added at this temperature. After the mixture had been stirred for a further 15 minutes, it was heated to (-20)~C and treated with 3.2 g (9 mmol) of 2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-15 2,4(lH,3H)pyrimi~;n~;on-3-yl)benzaldehyde. Stirring was then continued for 2 hours at room t~ _e~ature. For working-up, the reaction mixture was treated with 10 ml of dilute hydrochloric acid. The product was extracted with ethyl acetate. Finally, the ethyl acetate phase was separated off, dried over magnesium 20 sulfate and concentrated. The crude product was purified by means of MPLC on silica gel (eluent: hexane/ethyl acetate = 1:2).
Yield: 0.2 g.
25 Example 44 Diethyl 1-chloro-2-t2-chloro-4-fluoro-5-(5,6,7,8-tetrahydro-1,2,4-triazolot4,3-a]pyridine-3(2H)-on-2-yl)phenyl]vinyl-phosphonate (No. IKh.861) 30 1.4 g (16.8 mmol) of sodium acetate were added to a solution of 2 g (5.6 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-hydrazinophenyl)vinylphosphonate in 50 ml of acetonitrile.
After the mixture had been stirred for 30 minutes, it was cooled to 0~C and treated with 1.1 g (5.6 mmol) of methyl 35 2-iminopiperidine-1-carboxylate hydrochloride. The reaction mixture was subsequently stirred for 3 hours. It was then treated with 50 ml of water and 50 ml of ethyl acetate. The organic phase was separated off, dried over magnesium sulfate and finally concentrated.
The residue, which cont~;ne~ methyl 2-t2-(4-chloro-2-fluoro-5-t2-chloro-(2-diethylphosphoryl)vinyl]phenyl)hydrazin-1-yl-idene]piperidine-1-carboxylate, was dissolved in 50 ml of toluene and then treated with 0.1 ml of acetic acid. The mixture was 45 subsequently refluxed for 2 hours and then concentrated. The 0050/46~86 CA 0224~6~9 1998-08-06 , crude product obtained was purified by means of silica gel chromatography (eluent: ethyl acetate). Yield: 0.3 g.
Precursor 44.1 5 Diethyl l-chloro-2-(2-chloro-4-$1uorophenyl)vinylphosphonate (No. XXXIII.24) 462 ml (0.74 mol) of a 1.6-molar butyllithium solution (in 10 he~ne) were added to a solution, cooled to (-70)~C, of 408 g (1.6 mol) of diethyl trichloromethanephosphonate in 1.5 1 of tetrahydrofuran, whereupon the mixture was stirred for 1 hour at (-70)~C. 51 g (0.32 mol) of 2-chloro-4-fluorobenzaldehyde (dissolved in 200 ml of tetrahydrofuran) were subsequently added 15 dropwise to the mixture. The reaction mixture was then allowed to come to approximately 20~C, at which t- ~rature it was treated with 10 ml of water. Finally, the mixture was concentrated (under a high vacuum during the last phase). To purify the crude product, it was suspen~PA in 50 ml of hexane, and the solids were 20 filtered off. Concentration of the filtrate gave 47.5 g of the product of value.
H NMR (270 ~Hz; in CDCl3): ~ tppm] s 1.20-1.40 (m,6H), 4.10-4.30 (m,4H), 6.95-7.20 (m,2H), 7.45-7.95 (m,2H).
25 Precursor 44.2 Diethyl l-chloro-2-(2-chloro-4-fluoro-5-nitrophenyl)vinyl-phosphonate (~o. XXXII.36) 47.5 g (0.16 mol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-30 phenyl)vinylphosphonate were dissolved in 320 ml of co~centrated nitric acid at (-40)~C, whereupon the mixture was stirred for 1 hour. The reaction mixture was subsequently stirred into ~_ 2.5 1 of ice-water. The product was then extracted with dichloromethane. The organic phase was washed with saturated 35 aqueous sodium chloride solution, dried over magnesium sulfate and finally concentrated. The crude product was purified by means of MPLC on silica gel (eluent: hPx~ne/ethyl acetate = 2:1).
Yield: 33 g; lH NMR (270 MHz; in CDCl3): ~ lppml = 1.30-1.45 (m,6H), 4.10-4.30 (m,4H), 7.35-7.85 (m,2H), 8.30-8.70 (m,lH).
Precursor 44.3 Diethyl l-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinyl-phosphonate (No. XXXI.36) 17.5 g (47 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-nitrophenyl)vinylphosphonate were added at 60-65~C to a _ - OOS0/46586 CA 0224~6~9 1998-08-06 .
suspension of 13.1 g (0.24 mol) of iron powder in 40 ml of ethanol and 88 ml of acetic acid, whereupon the mixture was stirred for 2 hours at reflux temperature. The mixture was subsequently treated with 200 ml of ethyl acetate. The resulting 5 suspension was filtered through a Rieselguhr bed. The filtrate was then concentrated. The residue was dissolved in 200 ml of ethyl acetate. The organic phase was then washed with water, dried over magnesium sulfate and finally concentrated. Yield:
14.8 g; lH NMR (270 MHz; in CDCl3): ~ [ppm] = 1.41 (t,6H), 3.90 10 (s,2H), 4.20 (m,4H), 7.09 (d,lH), 7.37 (d,lH), 7.80 (d,lH).
Precursor 44.4 ~iethyl l-chloro-2-(2-chloro-4-fluoro-5-hydrazinophenyl)vinyl-phosphonate (No. XXVIII.36) ~_ 2.5 g (7.3 mmol) of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinylphosphonate were dissolved in 13.1 g of concentrated hydrochloric acid by briefly heating to 60~C. The 20 resulting solution was cooled to 0~C and treated with a solution of 0.5 g (7.3 mmol) of sodium nitrite in 1.5 ml of water. After the mixture had been stirred for 1 hour, a solution of 4.15 g (18.4 mmol) of tin(II) chloride dihydrate in 2.6 ml of concentrated hydrochloric acid was added dropwise. The mixture 25 was subsequently stirred for 2 hours at approximately 20~C. It was then diluted with 100 ml of water. The solids were filtered off.
The filtrate was rendered ~kAl;ne by adding 50 % strength sodium hydroxide solution. The product was extracted from the aqueous phase using three portions of 50 ml of dichloromethane. The 30 combined organic phases were washed with water, dried over magnesium sulfate and finally concentrated. Yield: 2 g; lH NMR
(270 MHz; in CDCl3): ~ [ppm] = 1.40 (t,6H), 3.60 (s,2H), 4.22 (m,4H), 5.48 (s,lH), 7.07 (d,lH), 7.73 (d,lH), 7.85 (d,lH).
35 Example 45 Diethyl l-chloro-2-(2-chloro-4-fluoro-5-[(3-methyl-4-trifluoro-methyl-2(3H)-thiazolylidene)amino]phenyl)vinylphosphonate (No. ILh.861) 40 0.3 g (3.5 mmol) of sodium acetate and 0.6 g (2.9 mmol) of 3-bromo-1,1,1-trifluoroacetone were added to a solution of 1.2 g (2.9 mmol) of diethyl 1-chloro-2-(2-chloro-4-fluoro-5-t(methyl-aminothiocarbonyl)amino~phenyl)vinylphosphonate in 50 ml of toluene, whereupon the mixture was refluxed for 1 week. The 45 reaction mixture was then washed with water, dried over magnesium sulfate and concentrated. The crude product was purified by means - 0050/46586 CA 0224~6~9 l998-08-06 of silica gel chromatography (eluent: hexane/ethyl acetate =
1:1). Yield: 0.2 g.
Precursor 45.1 5 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-[(methylaminothio-carbonyl)amino]phenyl)vinylphosphonate (No. XXXV.36) 1.2 g (16.4 mmol) of methyl isothiocyanate were added to a solution of 3 g (8.7 mmol) of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinylphosphonate in 50 ml of ethanol.
After the mixture had been stirred for 8 hours at reflux temperature, it was concentrated. The crude product was purified by means of silica gel chromatography (eluent: h~xAne/ethyl 15 scetate = 1:1). Yield: 1.3 g; 1H NMR (270 MHz; in CDCl3): ~ tppm]
= 1.41 (t,6H), 3.15 and 3.17 (2s, together 3H), 4.22 (m,4H), 6.40 ~ (s,lH), 7.29 (d,lH), 7.60 (s,lH), 7.81 (d,lH), 8.16 (s,lH).
t Example 46 20 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-((tetrahydro-3-oxo-lH,3H-[1,3,4]-~h; AA i A ~olo~3,4-a]pyridazin-1-ylidene)amino)phenyl)vinyl-phosphonate (No. IMh.861) 2.2 g (28 mmol) of pyridine and 1.4 g (7 mmol) of diphosgene were 25 added to a solution of 3.3 g (7 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-5-((hexahyd u~y ;~A~;n-1-ylthiocarbonyl)-amino)phenyl)vinylphosphonate in 100 ml of dichloromethane, wheLeu~on the mixture was stirred for 1 hour. The reaction mixture was subsequently washed with water, dried over magnesium 30 sulfate and concentrated. The crude product was purified by means of silica gel chromatography (eluent: he~Ane/ethyl acetate =
1:2). Yield: 1 g.
Precursor 46.1 35 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5-isothiocyanatophenyl)-vinylphosphonate (No. XL.36) 1.1 g (9.7 mmol) of thiophosgene and a solution of 3 g (8.7 mmol) 40 of diethyl 1-chloro-2-(5-amino-2-chloro-4-fluorophenyl)vinyl-phosphonate in 15 ml of dichloromethane were added to a solution of 1.6 g (19 mmol) of sodium hydrogen carbonate in 10 ml of water and 10 ml of dichloromethane, whereupon the mixture was stirred for 5 hours. The reaction mixture was subsequently washed with 45 water, dried over magnesium sulfate and concentrated. Yield: 3 g;
lH NMR (270 MHz; in CDCl3): ~ tppm] = 1.40 (t,6H), 4.22 (m,4H), 7.30 (d,lH), 7.74 (d,lH), 7.78 (d,lH).
-~ OOS0/46586 CA 0224~6~9 1998-08-06 , 181 _ Precursor 46.2 Diethyl 1-chloro-2-(2-chloro-4-fluoro-5[(hexahydropyridazin-l-yl-thiocarbonyl)amino]phenyl)vinylphosphonate (No. xx~TxA~36) 5 A solution of 3 g (8.7 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-S-isothiocyanatophenyl)vinylphosphonate in 20 ml of tetrahydrofuran was added to a solution of 0.8 g (9.3 mmol) of hexahydropyri~A7;ne in 20 ml of tetrahydrofuran, whereupon the mixture was stirred for 16 hours. The reaction mixture was then lO concentrated. The residue was treated with 50 ml of ethyl acetate. Finally, the organic phase was washed with water, dried over magnesium sulfate and concentrated. Yield: 3.3 g. The crude product was further reacted without further purification.
Example 47 Diethyl 1-chloro-2-(2-chloro-5-t(6,7-dihydro-6,6-dimethyl-3H,5H--pyrrolo--t2,1--c]tl,2,4]th;A~;A7-ol--3--yl;~ene)amino]--4-fluorophenyl)vinylphosphonate (No. INh.861) 10.5 g (26.4 mmol) of a 10 % strength by weight sodium hydlo~ide solution were added at 0-5~C to a solution of 1.3 g (8.8 mmol) of 5-amino-3,4-dihydro-3,3-dimethyl-2H ~ylLole hydrochloride in 50 ml of dichloromethane. After the mixture had been stirred for 25 one hour, it was treated with 2.5 g (6.5 mmol) of diethyl l-chloro-2-(2-chloro-4-fluoro-5-isothiocyanatophenyl)vinyl-phosphonate. The reaction mixture was subsequently stirred for 3 hours and then cooled to (-20)~C and treated with 1.2 g (6.9 mmol) of bromine. In order to react all reactants as 30 completely as possible, stirring was cont;n~eA for 16 hours at approximately 20~C. Finally, the organic phase was separated off, dried over magnesium sulfate and concentrated. The crude product was purified by means of silica gel chromatography (eluent:
h~Ane/ethyl acetate - 1:1). Yield: 1.7 g.
Example 48 Diisopropyl 1-bromo-2-t2-chloro-5-(4-chloro-5-difluoromethoxy-l-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]vinylphosphonate (No. Isi~863) and diisopLo~yl 2-t2-chloro-5-(4-chloro-40 5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]-ethynylphosphonate (No. IBn.863) Following the procedure described in Example 40 and using 3.4 g (8 mmol) of tetraisopropyl b~ Lhanediphosphonate, 0.2 g 45 (8 mmol) of sodium hydride and 1.6 g (4 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoro-benzaldehyde, a crude product is obt~;ne~ whose silica gel -~ 0050~46586 CA 0224~6~9 l998-08-06 chromatography first revealed 0.5 g of diisopropyl 1-bromo-2-l2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH ~yl dZOl -3-yl)-4-fluorophenyl]vinylphosphonate followed by 0.4 g of diisopropyl 2-l2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-5 lH-pyrazol-3-yl)-4-fluorophenyl]ethynylphosphonate.
Example 49 Diethyl 2-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fiuorophenyl]-1-cyanoethylphosphonate 10 (No. IBd.86l) 0.66 g (3.7 mmol) of diethyl cy~n~ -~hanephosphonate was added to a suspension of 80 mg (3.4 mmol) of sodium hydride in 50 ml of 15 tetrahydrofuran. After the mixture had been stirred for 10 minutes, it was treated with 1 g (2.5 mmol) of 2-chloro-5-~4-chloro-5-difluoromethoxy-1-methyl-lH ~yLazol-3-yl)-4-fluor C benzyl bromide. The mixture was subsequently stirred for 16 hours. The reaction mixture was subsequently concentrated.
The residue was treated with 100 ml of water and 100 ml of ethyl acetate. After the phases had been mixed, the organic phase was separated off, dried over magnesium sulfate and concentrated.
The crude product was purified by silica gel chromatography (eluent: ~e~ne/ethyl acetate - 4:1). Yield: 0.7 g.
Example 50 Methyl 3-[2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluorophenyl]-2-(diethylphosphoryl)propionate (No. IBf.861) Following the procedure described in Example 49 and using 80 mg (3.4 mmol) of sodium hydride, 0.78 g (3.7 mmol) of methyl diethylphosphorylacetate and 1 g (2.5 mmol) of 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-lH-pyrazol-3-yl)-4-fluoro-35 benzyl bromide, 0.7 g of the desired product of value were obt~;ne~.
In addition to the subst~nces described above, further aromatic phosphonic acid derivatives of the form~ I which were, or can 40 be, prepared in a similar ~nne~ are listed in Tables 9-20 below:
Table 9 - (/ \~= O
,~N yl IA {R3 = Cl, D
~ ~ Eth--P -- y2R1 R5 - ~pl~ O
R9 = (~F8 }
Cl y3R2 w ~
-Eth- -P(=Yl)(Y2RI)(Y3R2) M.p. / IH NMR (o in [ppm]) / MS [m/z]
IAb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 3.13 (dt, lH),3.56 (s, 3H), 3.66 (ddd, lH), 3.83 (d, 3H), 3.90 (d, 3H), 4.28 (dt, lH), 6.37 (s, lH), 7.12 (dd, lH), 7.21 (d, lH), 7.53 (d, lH) lAg.3 H -CH=CH- p(=O)(OC2Hs)2 96-98oc IAg.432 Cl -CH=CH- _p(=O)(Oc2Hs)2 150-lS~C
IAg.861 F -CH=CH- _p(=O)(OC2Hs)2 1.37 (t, 6H), 3.57 (s, 3H), 4.16 (quint, 4H), 6.20 (dd, lH), 6.39 (s, lH), 7.36 (d, lH), 7.52 (d, lH), 7.77 (dd, lH) No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (o in [ppm]) / MS [m/z] ~
IAh.3 H -CH=C(a)- -P(=o)(oc2Hs)2 1.19 and 1.40 (2t, together 6H), 3.54 and 3,56 (2s, together 3H), 4.22 (m, 4H), 6.34 and 6.38 (2s, together lH), 7.15 and 7.20 (2dd, together lH), 7.48 and 7.81 (2d, together G:~
lH), 7.50 and 7.90 (2d, together lH), 7.52 and 7.59 (2d, together lH) lAh.432 a -CH=C(a)- _p(=O)(OC2Hs)2 118-121~C
lAh.859 F -CH=C(CI)- -P(=O)(OH)2 3.42 (s, 3H), 6.60 (s, lH), 7.59 (d, lH), 7.86 (d, lH), 8.03 (d, lH) D
IAh.860 F -CH=C(a)- _p(=O)(OCH3)2 3.59 (s, 3H), 3.87 (d, 6H), 6.39 (s, lH), 7.40 (d, lH), 7.87 (d~ lH)~ 7-92 (d~ lH) IAh.861 F -CH=C(a)- -P(=o)(oc2Hs)2 518 [M]+, 483 [M-CI]+ '~
IAh.862 F -CH=¢(CI)- _p(=o)[o-(n-c3H7)]2 0.99 (t, 6H), 1.76 (sext, 4H), 3.58 (s,3H), 4.10 (quint, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.86 (d, lH), 7.93 (d, lH) O
IAh.863 F -CH=¢(a)- _p(=o)[OCH(CH3)2]2 1.36 (d, 6H), 1.41 (d, 6H), 3.58 (s, 3H), 4.77 (m, 2H), 6.38 ~
(s, lH), 7.37 (d, lH), 7.86 (d, lH), 7.90 (d, lH) lAh.864 F -CH=¢(a)- -P(=O)[O-(n-(iHs)]2 0.95 (t, 6H), 1.43 (sext, 4H), 1.72 (quint, 4H), 3.58 (s, 3H), 4.13 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.85 (d,lH), 7.93 (d, lH) IAh.865 F -CH=¢(a)- _p(=o)[ocH2-cH(cH3)2]2 0.98 (d, 12H), 2.03 (m, 2H),3.59 (s, 3H), 3.91 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.85 (d, lH), 7.93 (d, lH) No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (~ in [ppm]) / MS [m/z] ~
IAh.866 F -CH=C(CI)- _p(=o)[ocH(cH3)-c2Hs]2 0.95 and 0.98 (2t, together 6H), 1.35 and 1.40 (2d, together 6H), 1.65-1.80 (m, 4H), 3.58 (s,3H), 4.57 ,~
(m, 2H), 6.39 (s, lH), 7.39 (d, lH), 7.87 (d, lH), 7.89 '"
(d, lH
IAh.867 F -CH=C(CI)- _p(=o)(ocH2-cF3)2 3.57 (s, 3H), 4.50 (m, 4H), 6.38 (s, lH), 7.42 (d, lH), 7.94 (d, lH), 7.96 (d, lH) IAh.870 F -CH=C(CI)- -P(=O)(OCH2-CH2-OCH3)2 3.39 (s, 6H),3.56 (s, 3H),3.66 (t, 4H), 4.29 (m, 4H), 4.50 ~, (m, 4H), 6.38 (s, lH), 7.40 (d, lH), 7.88 (d, lH), 7.92 D
(d~ lH) IAh.890 F -CH=C(CI)- -P(=O)(OCH2-CH=CH2)2 3.57 (s, 3H),4.65 (m, 4H), 5.27 (d, 2H), 5.42 (d, 2H), 5.97 (m, 2H), 6.39 (s, lH), 7.39 (d, lH), 7.87 (d, lH), 7.92 ~O
(d, lH) ~-1Ah.894 F -CH=C(CI)- -P(=o)(ocH2-c- CH)2 2.64 (t, 2H), 3.57 (s, 3H), 4.82 (dd,4H), 6.38 (s, lH), 7.40 ~n ~
(d~ lH), 7.92 (d, lH), 7.95 (d, lH) ~O
IAh.896 F -CH=C(CI)- ~P(=o)(ocHrco-ocH3)2 3.58 (s, 3H), 3.81 (s, 6H), 4.74 (dd, 2H), 4.83 (dd, 2H), 6.38 (s, lH), 7.39 (d, lH), 7.84 (d, lH), 7.86 (d, lH) IAh.914 F -CH=C(CI)- -P(=O)(O-phenyl~ 3.58 (s,3H), 6.38 (s, lH), 7.15-7.40 (m, llH), 7.87 (d, lH), 7.99 (d, lH) IAh.1154 F -CH=C(CI)- _P(=o)(o-cH2-cH2-cH2-o) 2.08 (m, lH), 2.30 (m, lH), 3.57 (s, 3H), 4.58 (m, 4H), 6.38 (s, lH), 7.39 (d, lH), 7.82 (d, lH), 7.87 (d, lH) IAh.1155 F -CH=C(CI)- _p(=o)(o-cH2-c(cH3)2-cH2-o) 530 [M]+, 495 [M-CI]+
r. ~ .
No. R4 -Eth- _p(=yl)(y2Rl)(y3R2) M.p. / IH NMR (~ in [ppm]) / MS [m/z] ~
IAh.1256 F -CH=C(CI)- -P(=o)[N(cH3)-cH2-cH2-cH2-N(cH3)] 1.90 (m, lH), 2.20 (m, lH), 2.68 (d, 6H), 3.16 (m, 2H), 3.35 (m, 2H), 3.58 (s, 3H), 6.39 (s, lH), 7.37 (d, lH), 7.77 ~
(d, lH), 7.84 (d, lH) , "
IAi.863 F -CH=C(Br)- p(=o)[oCH(CH3)2]2 1.21 (d, 6H), 1.25 (d, 6H),3.55 (s, 3H), 4.78 (okt, 2H), 6.34 (s, lH), 7.31 (d, lH), 7.62 (d, lH), 7.70 (d, lH) IAj.861 F -CH=C(CN)- p(=O)(OC2Hs)2 1.42 (t, 6H), 3.57 (s, 3H), 4.25 (m, 4H), 6.38 (s, lH), 7.44 (d, lH), 8.26 (d, lH), 8.35 (d, lH) IAk.861 F -CH=C(CH3)- -P(=O)(OC2Hs)2 1.15 and 1.28 (2dt, together 6H), 1.95 and 2.15 (2dd, D
together 3H), 3.52 and 3.56 (2s, together 3H), 3.90 and ~
~ 4.10 (2m, together 4H), 6.31 and 6.36 (2s, together lH), ~
7.02 and 7.43 (2dd, together lH), 7.24, 7.30, 7.38 and 7.62 , (4d, together 2H) '~
Table l~ u F2HCO p Cl , / ~ Y~ 3 = Cl, R4 ~ Eth - p - y2Rl R5 ~2, \=( I Rll = OCHF2, ~
\ y3R2 Rl2 = Cl} D
Cl No. R4 -Eth- -P(=Y')(Y~R')(Y~R~) M.p./1H N M R (~in[ppm])/ MS[m/z]
IBa.861 F -cH2-cH2- _p(=o)(oc2Hs)2 474[M]+,439[M-CI~ ~ ~
IBb.431 Cl -CH2-CH(a)- _p(=O)(OCH3)2 3.11 (dt, lH),3.62 (ddd, lH),3.85(s,3H),3.87 (d, 3H), O
3.92 (d, 3H),4.27 (dt, lH),6.72 (t, lH),7.39(s,lH),7.53 (s,lH) IBb.860 F -CH2-CH(CI)- _p(=O)(OCH3)2 3.12 (ddd, lH),3.64 (ddd, lH),3.85(s,3H),3.87 (d, 3H), 3.91 (d, 3H),4.25 (dt, lH),6.71 (t, lH),7.26 (d,lH), 7.51 (d, lH) IBb.861 F -CH2-CH(CI)- -P(=o)(oc2Hs)2 1.39 (dt, 6H),3.11 (ddd, lH),3.65 (ddd, lH),3.84(s,3H), 4.20-4.30 (m, SH),6.71 (t, lH),7.25 (d, lH),7.52 (d, lH) IBc.860 F -CH2-CH(Br)- _p(=O)(OCH3)2 3.18 (ddd, lH),3.72 (ddd, lH),3.84(s,3H),3.87 (d, 3H), 3.92 (d, 3H),4.21 (dt, lH),6.71 (t, lH),7.25 (d,lH), 7.50 (d, lH) O050/46586 CA 02245659 l998-08-06 6 ~ 6 ~ ~ 66 ~ 6 ~O ~ ~
ac ~ i~+ ~ E~~~
~ 00 0 ~ ~C~ ~ .C ~ _, ~ ~ g ~ o~ O ~ ~ ~ ~ _1 z ~ ' ~ â ~
a~; m ~ m m~ m a~ m m ~m m .
_ o~ ~
o ~ ~ ~ ~ ~ ~ ~
ô o ~ ~, X
--I ~ ~_ O 0~ ~
~
ô ~
~) r~
_ _ ~O, _ U~ O O
O O O O O O
v ~3 ~) m ~ ~ ~ .
~z m m m m m m r~
Table 11 g Cl \N~J\ yl Ic {R3 = Cl, R4~ Eth--p -- y2Rl Rl~ - CH3, \=( ¦ Rl 1 = CF3, D
Cl Y3R2 R12 = Cl} - o !~
No. R4-Eth- -P(=Y')(Y~R')(Y~R~) M.p. / ~H NMR (o in [ppm]) / MS [m/z] ~D
ICa.863 F -cH2-cH2- -P(=o)(ocH(cH3)2)2 504 lM]+, 485 [M-E~l+, 469 [M-CI]+
ICg.861 F -CH=CH- _p(=O)(OC2Hs)2 1.38 (t, 6H), 4.09 (s, 3H), 4.16 (quint, 4H), 6.29 (t, lH), 7.29 (d, lH), 7.78 (d, lH), 7.83 (dd, lH) o ICh.859 F -CH=C(CI)- -P(=O)(OH)2 resin ICh.860 F -CH=C(CI)- -P(=O)(OCH3)2 89-93~C
ICh.861 F -CH=C(CI)- -P(=O)(Oc2Hs)2 62-65~C
ICh.862 F -CH=C(CI)- -P(=O)[O-(n-C3H7)]2 1.01 (t, 6H), 1.78 (sext, 4H), 4.09 (s, 3H), 4.14 (m, 4H), 7.34 (d, lH), 7.87 (d, lH), 8.13 (d, lH) ICh.863 F -CH=C(CI)- -P(=O)[OCH(CH3)2]2 1.39 (d, 6H), 1.43 (d, 6H), 4.08 (s, 3H), 4.79 (okt, 2H), 7.34 (d, lH), 7.88 (d, lH), 8.10 (d, lH) ~ . . _ ~~ o ~ ~ ~ ~o ~ 6 :~
~, 0. ~ .~
~ _ ~ ~, 8 ~~ ~ ~ ~ ~o ~ ~ ~~
Z ~?6 ~? 8 66 6 ~ V ~6 60,, -- ~ ~ ~ ~ ~ ~ ~ ~'~ 6 '-6 ~ o ~ o ~_ o _ ~ ~ ~
C
~- ~ ~ o o oo o z y~
~ o o o oo o o o c~ ~ l l l l l l l v v v vv v v ~
~l v v v v v v v v ~t ' z v v v v v ~ ~ ~
Table 12 - o CF3 yl ID ~R3 = C1, R4~ Eth--P -- y2R1 R5 ~2, \=(~ Rll = R12 = C
Cl y3R2 No.R4 -Eth- -P(=Y')(Y~R')(Y~R;~) M.p. / IH NMR (~ in [ppm]) / MS [m/z]
IDb.860 F -CH2-CH(CI)- -P(=O)(OCH3)2 98-101~C '~
Table 13 O
,~q R4~ Eth--P-- Y2RI y~ - o R13R14 = (CH2)4}
y3R2 D
Cl No. R4 -Eth- _p(=yl)(Y~Rl)(Y~R~) M.p. / lH NMR (~ in [ppm]) / MS [m/z]
IEb.2 H -CH2-CH(CI)- -P(=O)(OcH3)2 1.84 (s, 4H), 2.44 (s, 4H), 3.11 (dt, lH), 3.65 (ddd, lH), - 3.88 (d, 3H), 3.91 (d, 3H), 4.37 (dt, lH), 7.25 (dd, lH), - ~
7.35 (d, lH), 7.46 (d, lH) O
IEg.3 H -CH=CH- -P(=o)(oc2Hs)2 1.37 (t, 6H), 1.84 (s,4H), 2.46 (s, 4H),4.15 (quint, 4H), O
6.19 (t, 1 H), 7.35 (dd, lH), 7.48 (d, lH), 7.64 (d, lH), -7.85 (dd, lH) IEg.56 H -CH=CH- -P(=O)(O-phenyl~Q 124-126~C
IEh.3 H -CH=C(C!)- -P(=O)(OC2Hs)2 114-118~C
IEh.432 Cl -CH=C(CI)- -P(=O)(OC2Hs)2 1.40 (t, 6H), 1.86 (s, 4H), 2.47 (s, 4H), 4.20 (m, 4H), 7.64 (d, lH), 7.85 (s, lH), 7.86 (s, lH) IEb.860 F -CH2-CH(CI)- -P(=O)(OCH3)2 1.86 (s, 4H), 2.47 (s, 4H), 3.12 (dt, lH), 3.62 (ddd, lH), 3.85 (d, 3H), 3.90 (d, 3H), 4.20 (dt, lH), 7.25 (d, lH), 7.32 (d, lH) o ~-- ~ ~ ~ ~
~--@ ~ ~ ? ~
rC ~D ~? ~ ~C o r t~
~ O O
~_ '~ ~ O ~ O
_~ _ _ _ _ ~) m ~ ~OD
00 ~ 00 00 Z ~ ~ $ ~
Table 14 ~
H3C~f H3C ~/
6~N yl IF {R3 = Cl, O 1I R5 = <p3, R4~/ \~ Eth--P --Y2Rl y4 0 \~:( ¦ R13 = R14 = CH3}
y3R2 D
Cl No. R4 -Eth- -P(=Yl)(Y~R~)(YJR~) M.p. / IH NMR (~ in [ppm]) / MS [m/z]
IFg.3 H -CH=CH- -p(=o)(oc~Hs)2 736(dd,IH),749(d,IH);7.64(d,iH),7.g4(dd lH) ~
1Fh.3 H -CH=C(CI)- -P(=O)(Oc2Hs)2 124-126~C x .
Table 15 0 o O
I ~n N yl R~ th - P - YZRI Rs - ~4, Cl y3R2 Rl7 = Cl} D
No.R4 -Eth- -P(=Y')(Y'RI)(Y~R~) M.p./ 'H N M R (oin[ppm])/ MS[m/z] ~o IGb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 1.85 (m, 4H),2.52 (t, 2H),2.72 (t, 2H),3.15 (ddd, lH), 3.70 (ddd, lH),3.92 (d, 3H),3.95 (d, 3H),4.30 (dt, lH), 7.45(s,2H),7.55(s,lH) ~
IGb.3 H -CH2-CH(CI)- -P(=O)(Oc2Hs)2 1.37 (m, 6H),1.82 (m, 4H),2.52(t,2H),2.72(t,2H),3.13 ~
(ddd, lH),3.70 (ddd, lH),4.20-4.35(m,SH),7.47 (s,2H),7.54(s,lH) IGb.860 F-CH2-CH(CI)- -P(=O)(OCH3)2 1.82 (m, 4H),2.51(t,2H),2.71 (t, 2H),3.11 (ddd, lH), 3.63 (ddd, lH),3.88 (d, 3H),3.92 (d, 3H),4.25 (dt, lH), 7.32 (d, lH),7.44 (d, lH) - Q r~ ~
Table 16 o F2HC Cl N
H3C~ yl . .
N~ IH {R3 z Cl /~ 1I R5 a (p5 ~
R4~/ \~ Eth--P -- Y2Rl R18 = Cl, \=( ¦ R19 = CHF2, Cl y3R2 R20 = CH3 } D
No. R4 -Eth- -P(=Yl)(y'Rl)(y~R~) M.p. / lH NMR (o in [ppm]) / MS [m/z] ~0 IHb.2 H -CH2-CH(CI)- -P(=O)(OCH3)2 2.62 (s, 3H), 3.15 (ddd, lH), 3.70 (ddd, lH), 3.88 (d, 3H), ~o 3.94 (d, 3H), 4.34 (dt, lH), 7.15 (t, lH), 7.M (d, lH), 7.79 (dd, lH), 7.87 (d, lH) ~
Table 17 o o ~NJ~ N yl a~
R4~ Eth--P -- Y2RI IR ~R3 ~ Cl \~ R23R24 - (CH2 ) 4}
Cl y3R2 D
No. R4 -Eth- -P(=Y~)(Y~RI)(Y~R~) M.p. / 'H NMR (~ in [ppm]) / MS [m/z] n IKh.861 F -CH=C(CI)- -P(=O)(OC2Hs)2 1.41 (t, 6H), 1.96 (m, 4H), 2.79 (t, 2H), 3.72 (t, 2H), 4.23 (q, 4H), 7.36 (d, lH), 7.84 (d, lH), 8.15 (d, lH) cl~
Table 18 0 CF3 ~
S~,N~ yl , N 11 IL {R3 = Cl, R4~ Eth--P --y2RlR5 ~20, 51 = CF3, ~
Cl y3R2 R52 = H} D
. .~
No. R4 -Eth- -P(=YI)(Y~R')(Y~R~) M.p. / IH NMR (o in [ppml) / MS [m/z] ~0 ILh.861 F -CH=C(CI)-! -P(=O)(O~zHs)2 1.40 (~, 6H), 3.57 (s, 3H), 4.~ (m, 4H), 6.58 (s, lH), 7.24 (d, lH), 7.69 (d, lH), 7.86 (d, lH) r ~ . .
Table 19 g O ' o ~N
~N~, S
~ Il yl r~
N IM {R3 = Cl, ~ ¦¦ .R5 = ~21, R4~/ \~ Eth--P -- Y2R1 z3 = z4 = N, \=~ R53R54 = ( CH2 ) 4 }
C1 y3~2 No. R4 -Eth- -P(=Y')(Y~R')(YJR~) M.p. / lH NMR (o in [ppm]) / MS ~m/z] ~O
IMh.861 F -CH=C(Cl)- -P(=O)(OC2Hs)2 1.41 (t, 6H), 1.80-2.00 (m,4H), 3.75 (t, 2H), 3.84 (t,2H), o 4.22 (m, 4H), 7.24 (d,lH), 7.57 (d,lH), 7.84 (d, IH) '~
r~
Table 2 0 0 H3C >~N
H3C N I yl N IN {R3 = Cl, ~ 1I R5 = ~22, R4~/ \~ Eth--P-- Y2Rl R55R56 =
CH2 -C ( CH3 ) 2 -CH2 - }
Cl y3R2 D
~, No. R4 -Eth- _p(=yl)(Y2R~)(Y3R~) M.p. / lH NMR (~ in [ppm]) / MS [m/z] N
INh.861 F -CH=C(CI)- -P(=O)(OC2HS)2 117-120~C . o x x - , OOSO/46586 CA 0224~659 1998-08-06 Use examples (herbicidal activity) 5 The herbicidal activity of the substituted aromatic phosphonic acid derivatives I was demonstrated by the greenhouse experiments which follow:
The culture cont~in~rs used were plastic flower pots contA;ning 10 loamy sand with approximately 3.0 ~ of humus as the substrate.
The seeds of the test plants were sown separately for each species.
For pre .~ -rgence treatment, the active ingredients, which had 15 been suspended or emulsified in water, were applied by means of finely distributing nozzles directly after sowing. The cont~;n~rs ~~ were irrigated gently to promote ger~;n~tion and growth and subsequently covered with translucent plastic hoods until the plants had rooted. This cover causes uniform g~rmin~tion of the Z0 test plants unless this was adversely affected by the active in-gredients.
For post-emergence treatment, the test plants were first grown to a plant height of 3 to lS cm, ~ep~n~ing on the plant habit, and 25 only then treated with the active ingredients which had been sus-pended or emulsified in water. The test plants were either sown directly and grown in the same cont~iners~ or they were first grown separately as seedlings and transplanted into the test con-tainers a few days prior to treatment. The rate of application 30 for the post-emergence treatment was 15.6, 7.8, 1.9 or 0.9 g of a.s. (active substance)/ha.
.., ~~ Depending on the species, the plants were kept at from 10 to 25~C
35 or from 20 to 35~C. The test period exten~e~ over 2 to 4 weeks.
During this time, the plants were ten~e~, and their response to the individual treatments was evaluated.
Evaluation was effected using a scale of from 0 to 100. 100 means 40 no emergence of the plants or complete destruction of at least the aerial parts, and 0 means no damage or normal course of growth.
The plants used in the greenhouse experiments belonged to the 45 following species:
-Scit~ntific name Common name Oryza sativa rice Abutilon theophrasti velvet leaf S ~m~ redroot pigweed retroflexus Chenopodium album lambs~lucu~
(goosefoot) 10 Galium aparine catcL~icd l~ed~ w Ipomoea subspecies morning glory Polygonum persicaria lady's thumb Solanum nigrum black ni~ht!ih~
15 Veronica ~ubs~ccies speedwell - At rates of application of 1.9 and 0.9 g of a.s./ha, compound No.
IBg.861 applied post-emergence showed a selective herbicidal ac-tivity against Abutilon theophrasti, Amaranthus retroflexus and 20 Solanum nigrum in the crop rice, which was only damaged to a minor extent.
Compounds No. IBh.861 and No. IAh.861, applied post-emergence at the same rates of application, showed a very good activity 25 against Abutilon theophrasti, Amaranthus retroflexus and Solanum nigrum.
At rates of application of 15.6 and 7.8 g of a.S./ha, compounds No. IBg.861, IBh.861 and IAh.861 control Amaranthus retroflexus, 30 Chenopodium album, Galium aparine and Solanum nigrum better than the co~r~ison o~...~ound A, which is known from ASC Symp. Ser. 584 (1995), go Cl ~ Cl Cl ~
CH2 - CH p ~C2Hs (A) ~N~N
F2HC ~C2Hs - 0050/46586 CA 022456~9 1998-08-06 Use examples (desiccant/defoliant activity) The test plants used were young cotton plants with 4 leaves (without cotyledons) which had been grown under greenhouse condi-5 tions (relative humidity 50 to 70 %; day/night t~mp~rature 27/20~C).
The young cotton plants were subjected to foliar treatment to 10 drip point with aqueous preparations of the active ingredients (with an addition of 0.15 % by weight of the fatty alcohol al-koxylate Plurafac LF~ 7001, based on the spray mixture). The amount of water applied was 1000 l/ha (converted). After 13 days, the number of shed leaves and the degree of defoliation in % were det~r~; ne~ .
No leaves were shed in the untreated control plants.
1) a low-foam, non-ionic surfactant from sASF AG
Claims (38)
1. A substituted aromatic phosphonic acid derivative of the formula I
where the variables have the following meanings:
Eth is 1,2-ethynediyl or an ethane- or ethene-1,2-diyl chain, each of which can be unsubstituted or have attached to it one or two of the following substituents: halogen, cyano, carboxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, (C1-C4-alkoxy)carbonyl and/or di(C1-C4-alkyl)amino, it being possible for the ethane-1,2-diyl chain, if desired, additionally to have attached to it a hydroxyl, amino or C1-C4-alkylamino group;
y1 is oxygen or sulfur;
y2 is oxygen, sulfur or -N(R6)-;
y3 is oxygen, sulfur or -N(R7)-;
R1, R2, R6 and R7 independently of one another are hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, hydroxy-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl,C1-C4-haloalkoxy-C1-C4-alkyl, C3-C4-alkenyloxy-C1-C4-alkyl, C3-C4-alkynyloxy-C1-C4-alkyl, C3-C8-cycloalkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, di(C1-C4-alkyl)amino-C1-C4-alkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-haloalkylthio-C1-C4-alkyl, C3-C4-alkenylthio-C1-C4-alkyl, C3-C4-alkynylthio-C1-C4-alkyl, C1-C4-alkylsulfinyl-C1-C4-alkyl, C1-C4-haloalkylsulfinyl-C1-C4-alkyl, C3-C4-alkenyl-sulfinyl-C1-C4-alkyl, C3-C4-alkynylsulfinyl-C1-C4-alkyl, C1-C4-alkylsulfonyl-C1-C4-alkyl, C1-C4-haloalkylsulfonyl-C1-C4-alkyl, C3-C4-alkenyl-sulfonyl-C1-C4-alkyl, C3-C4-alkynylsulfonyl-C1-C4-alkyl, C3-C6-alkenyl, C3-C6-haloalkenyl, cyano-C3-C6-alkenyl, C3-C6-alkynyl, C3-C6-haloalkynyl, cyano-C3-C6-alkynyl, hydroxycarbonyl-C1-C4-alkyl, (C1-C4-alkoxy)carbonyl-C1-C4-alkyl, (C1-C4-alkylthio)carbonyl-C1-C4-alkyl, aminocarbonyl -C1-C4-alkyl, (C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, di(C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C4-alkyl, phenyl, phenyl-C1-C4-alkyl or 3- to 7-membered heterocyclyl or heterocyclyl-C1-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or thiocarbonyl ring member, and it being possible for all cycloalkyl, phenyl and heterocyclyl rings to be unsubstituted or to have attached to them one to four substituents, in each case selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, carboxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, C1-C4-alkylsulfonyl, C1-C4-haloalkylsulfonyl, (C1-C4-alkyl)carbonyl, (C1-C4-haloalkyl)carbonyl, (C1-C4-alkoxy)carbonyl, (C1-C4-alkyl)carbonyloxy, (C1-C4-haloalkyl)carbonyloxy and di(C1-C4-alkyl)amino, or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethanediyl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four C1-C4-alkyl and/or one or two (C1-C4-alkoxy)carbonyl groups, or R1 and R2 together are 1,2-phenylene which can be unsubstituted or have attached to it one to three substituents, in each case selected from the group consisting of cyano, nitro, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy;
R3 is cyano, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy or C1-C4-haloalkoxy;
R4 is hydrogen or halogen;
R5 is one of the following heterocycles .PHI.1 to .PHI.20:
where R8 is hydrogen, amino, C1-C4-alkyl or C1-C4-haloalkyl;
R9 is cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkylsulfonyl or C1-C4-haloalkylsulfonyl;
R10 is C1-C4-alkyl or C1-C4-haloalkyl;
R11 is cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, C1-C4-alkylsulfinyl, C1-C4-haloalkylsulfinyl, C1-C4-alkylsulfonyl or C1-C4-haloalkylsulfonyl, or R10 and R11 together with the ring atoms linking them are a 5- to 7-membered heterocycle which has one or two hetero atoms and which can be unsubstituted or have attached to it one or two C1-C4-alkyl radicals;
R12 is hydrogen, cyano, halogen, C1-C4-alkyl or C1-C4-haloalkyl;
Y4 is oxygen, sulfur or methylene;
R13, R14, R25, R26, R27, R28, R30 and R31 independently of one another are hydrogen or C1-C4-alkyl, or R13 and R14 together with the ring atoms linking them are a 5- to 7-membered carbo- or heterocyclic ring, it being possible for the ring, if desired, additionally to have attached to it one or two halogen and/or C1-C4-alkyl radicals or a further, fused 3- to 6-membered carbo- or heterocyclic ring;
R15 and R16 independently of one another are hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl, or R15 and R16 together with the ring atoms linking them are a 5- to 7-membered carbo- or heterocyclic ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl radicals;
R17 is halogen or C1-C4-alkyl;
R18, R33 and R35 independently of one another are halogen;
R19, R20, R29, R37, R38, R39, R40, R41, R42, R44, R55 and R56 independently of one another are hydrogen, C1-C4-alkyl or C1-C4-haloalkyl, or R19 and R20 and/or R39 and R40 and/or R41 and R42 and/or R55 and R56 together with the ring atoms linking them are a 5- to 7-membered ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl or C1-C4-haloalkyl radicals;
Y5, Y6, Y7, Y9 and Y10 independently of one another are oxygen or sulfur;
Z1, Z2, Z3 and Z4 independently of one another are nitrogen or CH;
R21 and R22 and/or R23 and R24 and/or R53 and R54 together with the ring atoms linking them are a 5- to 7-membered ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl radicals;
R32, R34, R48, R49 and R52 independently of one another are hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl or C1-C4-haloalkyl;
Y8 is oxygen or =NH;
R36 is hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C1-C4-haloalkoxy;
R43 is C1-C4-alkyl; and R45, R46, R47, R50 and R51 independently of one another are C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl or an agriculturally useful salt of a compound I, with the exception of those compounds I where R4 is hydrogen and R5 is .PHI.2.
where the variables have the following meanings:
Eth is 1,2-ethynediyl or an ethane- or ethene-1,2-diyl chain, each of which can be unsubstituted or have attached to it one or two of the following substituents: halogen, cyano, carboxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, (C1-C4-alkoxy)carbonyl and/or di(C1-C4-alkyl)amino, it being possible for the ethane-1,2-diyl chain, if desired, additionally to have attached to it a hydroxyl, amino or C1-C4-alkylamino group;
y1 is oxygen or sulfur;
y2 is oxygen, sulfur or -N(R6)-;
y3 is oxygen, sulfur or -N(R7)-;
R1, R2, R6 and R7 independently of one another are hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, hydroxy-C1-C4-alkyl, cyano-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl,C1-C4-haloalkoxy-C1-C4-alkyl, C3-C4-alkenyloxy-C1-C4-alkyl, C3-C4-alkynyloxy-C1-C4-alkyl, C3-C8-cycloalkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, di(C1-C4-alkyl)amino-C1-C4-alkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-haloalkylthio-C1-C4-alkyl, C3-C4-alkenylthio-C1-C4-alkyl, C3-C4-alkynylthio-C1-C4-alkyl, C1-C4-alkylsulfinyl-C1-C4-alkyl, C1-C4-haloalkylsulfinyl-C1-C4-alkyl, C3-C4-alkenyl-sulfinyl-C1-C4-alkyl, C3-C4-alkynylsulfinyl-C1-C4-alkyl, C1-C4-alkylsulfonyl-C1-C4-alkyl, C1-C4-haloalkylsulfonyl-C1-C4-alkyl, C3-C4-alkenyl-sulfonyl-C1-C4-alkyl, C3-C4-alkynylsulfonyl-C1-C4-alkyl, C3-C6-alkenyl, C3-C6-haloalkenyl, cyano-C3-C6-alkenyl, C3-C6-alkynyl, C3-C6-haloalkynyl, cyano-C3-C6-alkynyl, hydroxycarbonyl-C1-C4-alkyl, (C1-C4-alkoxy)carbonyl-C1-C4-alkyl, (C1-C4-alkylthio)carbonyl-C1-C4-alkyl, aminocarbonyl -C1-C4-alkyl, (C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, di(C1-C4-alkyl)aminocarbonyl-C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C4-alkyl, phenyl, phenyl-C1-C4-alkyl or 3- to 7-membered heterocyclyl or heterocyclyl-C1-C4-alkyl, it being possible for all heterocycles, if desired, to contain a carbonyl or thiocarbonyl ring member, and it being possible for all cycloalkyl, phenyl and heterocyclyl rings to be unsubstituted or to have attached to them one to four substituents, in each case selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, carboxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, C1-C4-alkylsulfonyl, C1-C4-haloalkylsulfonyl, (C1-C4-alkyl)carbonyl, (C1-C4-haloalkyl)carbonyl, (C1-C4-alkoxy)carbonyl, (C1-C4-alkyl)carbonyloxy, (C1-C4-haloalkyl)carbonyloxy and di(C1-C4-alkyl)amino, or R1 and R2 or R1 and R6 and/or R2 and R7 in each case together form a 1,2-ethanediyl, 1,3-propylene, tetramethylene, pentamethylene or ethyleneoxyethylene chain which, if desired, can be substituted by one to four C1-C4-alkyl and/or one or two (C1-C4-alkoxy)carbonyl groups, or R1 and R2 together are 1,2-phenylene which can be unsubstituted or have attached to it one to three substituents, in each case selected from the group consisting of cyano, nitro, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy;
R3 is cyano, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy or C1-C4-haloalkoxy;
R4 is hydrogen or halogen;
R5 is one of the following heterocycles .PHI.1 to .PHI.20:
where R8 is hydrogen, amino, C1-C4-alkyl or C1-C4-haloalkyl;
R9 is cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkylsulfonyl or C1-C4-haloalkylsulfonyl;
R10 is C1-C4-alkyl or C1-C4-haloalkyl;
R11 is cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, C1-C4-alkylsulfinyl, C1-C4-haloalkylsulfinyl, C1-C4-alkylsulfonyl or C1-C4-haloalkylsulfonyl, or R10 and R11 together with the ring atoms linking them are a 5- to 7-membered heterocycle which has one or two hetero atoms and which can be unsubstituted or have attached to it one or two C1-C4-alkyl radicals;
R12 is hydrogen, cyano, halogen, C1-C4-alkyl or C1-C4-haloalkyl;
Y4 is oxygen, sulfur or methylene;
R13, R14, R25, R26, R27, R28, R30 and R31 independently of one another are hydrogen or C1-C4-alkyl, or R13 and R14 together with the ring atoms linking them are a 5- to 7-membered carbo- or heterocyclic ring, it being possible for the ring, if desired, additionally to have attached to it one or two halogen and/or C1-C4-alkyl radicals or a further, fused 3- to 6-membered carbo- or heterocyclic ring;
R15 and R16 independently of one another are hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl, or R15 and R16 together with the ring atoms linking them are a 5- to 7-membered carbo- or heterocyclic ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl radicals;
R17 is halogen or C1-C4-alkyl;
R18, R33 and R35 independently of one another are halogen;
R19, R20, R29, R37, R38, R39, R40, R41, R42, R44, R55 and R56 independently of one another are hydrogen, C1-C4-alkyl or C1-C4-haloalkyl, or R19 and R20 and/or R39 and R40 and/or R41 and R42 and/or R55 and R56 together with the ring atoms linking them are a 5- to 7-membered ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl or C1-C4-haloalkyl radicals;
Y5, Y6, Y7, Y9 and Y10 independently of one another are oxygen or sulfur;
Z1, Z2, Z3 and Z4 independently of one another are nitrogen or CH;
R21 and R22 and/or R23 and R24 and/or R53 and R54 together with the ring atoms linking them are a 5- to 7-membered ring which, if desired, can additionally have attached to it one or two C1-C4-alkyl radicals;
R32, R34, R48, R49 and R52 independently of one another are hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl or C1-C4-haloalkyl;
Y8 is oxygen or =NH;
R36 is hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C1-C4-haloalkoxy;
R43 is C1-C4-alkyl; and R45, R46, R47, R50 and R51 independently of one another are C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl or an agriculturally useful salt of a compound I, with the exception of those compounds I where R4 is hydrogen and R5 is .PHI.2.
2. A substituted aromatic phosphonic acid derivative of the formula I or a salt thereof as claimed in claim 1 where R5 is a heterocycle .PHI.1, .PHI.2, .PHI.3, .PHI.4, .PHI.5, .PHI.7, .PHI.20, .PHI.21 or .PHI.22.
3. A substituted aromatic phosphonic acid derivative of the formula I or a salt thereof as claimed in claim 1 where R5 is 1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedion-3-yl, 4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl, 4-chloro-1-methyl-5-trifluoromethyl-1H-pyrazol-3-yl, 1-methyl-4,5-di(trifluoromethyl)-1H-pyrazol-3-yl, 1,3,4,5,6,7-hexahydro-1,3-dioxo-2H-isoindol-2-yl, 3,4-dimethyl-1H-pyrrol-2,5-dion-1-yl, 3-chloro-4,5,6,7-tetrahydro-2H-indazol-2-yl, 5-chloro-1-difluoromethyl-2-methyl-1H-imidazol-4-yl, 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-on-2-yl, (3-methyl-4-trifluoro-methyl-2(3H)-thiazolylidene)amino, (tetrahydro-3-oxo-1H,3H-[1,3,4]thiadiazolo[3,4-a]pyridazin-1-ylidene)amino or (6,7-dihydro-6,6-dimethyl-3H,5H-pyrrolo[2,1-c][1,2,4]
thiadiazol-3-ylidene)amino.
thiadiazol-3-ylidene)amino.
4. The use of a substituted aromatic phosphonic acid derivative I or a salt thereof as claimed in claims 1 to 3 as a herbicide or for the desiccation/defoliation of plants.
5. A herbicidal composition comprising a herbicidally active amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 and at least one liquid and/or solid carrier and, if desired, at least one surfactant.
6. A composition for the desiccation and/or defoliation of plants, comprising such an amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 that it acts as a desiccant and/or defoliant, and at least one inert liquid and/or solid carrier and, if desired, at least one surfactant.
7. A process for the preparation of herbicidally active compositions, which comprises mixing a herbicidally active amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 with at least one liquid and/or solid carrier and, if desired, at least one surfactant.
8. A process for the preparation of compositions which act as desiccants and/or defoliants, which comprises mixing such an amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 that it acts as a desiccant/defoliant with at least one liquid and/or solid carrier and, if desired, at least one surfactant.
9. A method of controlling undesirable vegetation, which comprises allowing a herbicidally active amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 to act on plants, their environment or on seed.
10. A method of desiccating and/or defoliating plants, which comprises allowing such an amount of at least one substituted aromatic phosphonic acid derivative of the formula I or of a salt of I as claimed in claims 1 to 3 to act on plants that it acts as a desiccant/defoliant.
11. A method as claimed in claim 10, which comprises the treatment of cotton.
12. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claims 1 to 3, where Eth is -CH2-CH(Cl)-, -CH2-CH(Br)-, -CH=C(Cl)- or -CH=C(Br)-, which comprises diazotizing anilines of the formula II
where R3, R4 and R5 have the meanings given in claim 1 and reacting the resulting diazonium cations, in the presence of a copper salt, with vinylphosphonic acid derivatives of the formula IIIa or with alkynylphosphonic acid derivatives of the formula IIIb where Y1, Y2, Y3, R1 and R2 have the meanings given in claim 1.
where R3, R4 and R5 have the meanings given in claim 1 and reacting the resulting diazonium cations, in the presence of a copper salt, with vinylphosphonic acid derivatives of the formula IIIa or with alkynylphosphonic acid derivatives of the formula IIIb where Y1, Y2, Y3, R1 and R2 have the meanings given in claim 1.
13. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is -CH=C(CN)- or -CH=C[CO-O-(C1-C4-alkyl)]-, which comprises reacting either aromatic aldehydes of the formula VIa where R3, R4 and R5 have the meanings given in claim 1 with phosphonic acid derivatives VIIa or VIIb where Y1, Y2, Y3, R1 and R2 have the meanings given in claim 1, or phosphonic acid derivatives of the formula XVIa or XVIb where Y1, Y2, Y3, R1 and R2 have the meanings given in claim 1 with 3-pyridylbenzyl halides of the formula XVII
where R3, R4 and R5 have the meanings given in claim 1 in the presence of a strong base.
where R3, R4 and R5 have the meanings given in claim 1 in the presence of a strong base.
14. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is -CH=CH-, -CH=C(halogen)- or -CH=C(C1-C4-alkyl)-, which comprises reacting aldehydes of the formula VIa where R3, R4 und R5 have the meanings given in claim 1 with anions VIIIa, VIIIb or VIIIc where Y1, Y2, Y3, R1 and R2 have the meanings given in claim 1.
15. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is -CH=CH-, which comprises reacting aromatic aldehydes of the formula VIa with ylides IX
where Y1, Y2, Y3, R1 to R5 have the meanings given in claim 1 and Ph is phenyl.
where Y1, Y2, Y3, R1 to R5 have the meanings given in claim 1 and Ph is phenyl.
16. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is -CH=CH- or -CH=C(C1-C4-alkyl)-, which comprises reacting phosphonic acid derivatives of the formula X
where Y1, Y2, Y3, R1 und R2 have the meanings given in claim 1 with chlorotrimethylsilane and aromatic aldehydes of the formula VIa where R3, R4 and R5 have the meanings given in claim 1 in the presence of a strong base.
where Y1, Y2, Y3, R1 und R2 have the meanings given in claim 1 with chlorotrimethylsilane and aromatic aldehydes of the formula VIa where R3, R4 and R5 have the meanings given in claim 1 in the presence of a strong base.
17. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is -CH=C(Cl)-, which comprises reacting aldehydes of the formula VIa where R3, R4 und R5 have the meanings given in claim 1 with trichloromethanephosphonic acid derivatives XXVI
where Y1, Y2, Y3, R1 und R2 have the meanings given in claim 1 in the presence of an alkyllithium compound XXVII
(C1-C4-alkyl)-Li XXVII.
where Y1, Y2, Y3, R1 und R2 have the meanings given in claim 1 in the presence of an alkyllithium compound XXVII
(C1-C4-alkyl)-Li XXVII.
18. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Eth is ethane-1,2-diyl, which comprises hydrogenating a compound of the formula I where Eth is an ethane-1,2-diyl or ethene-1,2-diyl chain which can be substituted by chlorine, bromine or iodine with hydrogen in the presence of a catalyst.
19. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Y1, Y2 and Y3 are oxygen and R1 and R2 are hydrogen, which comprises either hydrolyzing compounds of the formula I where Y1, Y2 and Y3 are in each case oxygen and R1 and R2 are in each case C1-C6-alkyl with a hydrohalic acid, or first reacting compounds of the formula I where Y1, Y2 and Y3 are in each case oxygen and R1 and R2 are in each case C1-C6-alkyl with a tri(C1-C4-alkyl)silyl halide and then hydrolyzing the product with water.
20. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where Y1 is oxygen, which comprises chlorinating compounds of the formula I where Y1, Y2 and Y3 are oxygen and R1 and R2 are hydrogen and subsequently reacting the products XXIVa with nucleophiles HY2R1 and/or HY3R2.
21. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where R5 is .PHI.7 where Y7 = oxygen, which comprises reacting phenylhydrazines of the formula XXVIII or acid addition salts thereof where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1 with amidines of the formula XXIXa or acid addition salts thereof where Y7 is oxygen and R23 and R24 have the meanings given in claim 1 in the presence of a base and cyclizing the reaction product by means of acid.
22. A phenylhydrazine of the formula XXVIII
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
23. A process for the preparation of phenylhydrazines of the formula XXVIII
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises diazotizing anilines of the formula XXXI
and reducing the resulting diazonium cations.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises diazotizing anilines of the formula XXXI
and reducing the resulting diazonium cations.
24. An aniline of the formula XXXI
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
25. A process for the preparation of anilines of the formula XXXI
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reducing corresponding nitro compounds of the formula XXXII
.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reducing corresponding nitro compounds of the formula XXXII
.
26. A nitro compound of the formula XXXII
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
27. A process for the preparation of nitro compounds of the formula XXXII
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises nitrating corresponding aromatic phosphonic acid derivatives of the formula XXXIII
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises nitrating corresponding aromatic phosphonic acid derivatives of the formula XXXIII
28. An aromatic phosphonic acid derivative of the formula XXXIIIa where Eth, Y1, Y2, Y3 and R1-R3 have the meanings given in claim 1 and R4' is halogen.
29. A process for the preparation of aromatic phosphonic acid derivatives of the formula XXXIII
where Eth is -CH=C(Cl)-and Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reacting aldehydes of the formula XXXIV
with trichloromethanephosphonic acid derivatives XXVI
in the presence of an alkyllithium XXVII
(C1-C4-alkyl)-Li XXVII.
where Eth is -CH=C(Cl)-and Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reacting aldehydes of the formula XXXIV
with trichloromethanephosphonic acid derivatives XXVI
in the presence of an alkyllithium XXVII
(C1-C4-alkyl)-Li XXVII.
30. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where R5 is .PHI.20 which comprises reacting thiourea derivatives of the formula XXXV
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1 with ketones of the formula XXXVI
where R51 and R52 have the meanings given in claim 1 in the presence of a base.
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1 with ketones of the formula XXXVI
where R51 and R52 have the meanings given in claim 1 in the presence of a base.
31. A thiourea derivative of the formula XXXV
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1.
32. A process for the preparation of thiourea derivatives of the formula XXXV
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1, which comprises reacting anilines of the formula XXXI
with isothiocyanates of the formula XXXVIII
SCN-R50 XXXVIII.
where Eth, Y1, Y2, Y3, R1-R4 and R50 have the meanings given in claim 1, which comprises reacting anilines of the formula XXXI
with isothiocyanates of the formula XXXVIII
SCN-R50 XXXVIII.
33. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where R5 is .PHI.21 and Z3 and Z4 are in each case nitrogen, which comprises reacting thiosemicarbazide derivatives of the formula XXXIX
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1 with phosgene, diphosgene or triphosgene in the presence of a base.
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1 with phosgene, diphosgene or triphosgene in the presence of a base.
34. A thiosemicarbazide derivative of the formula XXXIX
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1.
35. A process for the preparation of thiosemicarbazide derivatives of the formula XXXIX
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1, which comprises reacting corresponding isothiocyanates of the formula XL
with hydrazines of the formula XLI
where Eth, Y1, Y2, Y3, R1-R4, R53 and R54 have the meanings given in claim 1, which comprises reacting corresponding isothiocyanates of the formula XL
with hydrazines of the formula XLI
36. An isothiocyanate of the formula XL
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1.
37. A process for the preparation of isothiocyanates of the formula XL
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reacting corresponding anilines of the formula XXXI
with thiophosgene in the presence of a base.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1, which comprises reacting corresponding anilines of the formula XXXI
with thiophosgene in the presence of a base.
38. A process for the preparation of substituted aromatic phosphonic acid derivatives of the formula I as claimed in claim 1 where R5 is .PHI.22, which comprises reacting isothiocyanates of the formula XL
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1 with amidines of the formula XLII or XLIII
where R55 and R56 have the meanings given in claim 1 or with the acid addition salts thereof in the presence of a base and oxidizing the reaction products.
where Eth, Y1, Y2, Y3 and R1-R4 have the meanings given in claim 1 with amidines of the formula XLII or XLIII
where R55 and R56 have the meanings given in claim 1 or with the acid addition salts thereof in the presence of a base and oxidizing the reaction products.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19605765.5 | 1996-02-16 | ||
| DE19605765 | 1996-02-16 | ||
| PCT/EP1997/000733 WO1997030060A1 (en) | 1996-02-16 | 1997-02-17 | Substituted aromatic phosphonic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2245659A1 true CA2245659A1 (en) | 1997-08-21 |
Family
ID=29421552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2245659 Abandoned CA2245659A1 (en) | 1996-02-16 | 1997-02-17 | Substituted aromatic phosphonic acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2245659A1 (en) |
-
1997
- 1997-02-17 CA CA 2245659 patent/CA2245659A1/en not_active Abandoned
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