CA2000165A1 - N-sulfenylated and n-acylated pyrazolines - Google Patents
N-sulfenylated and n-acylated pyrazolinesInfo
- Publication number
- CA2000165A1 CA2000165A1 CA 2000165 CA2000165A CA2000165A1 CA 2000165 A1 CA2000165 A1 CA 2000165A1 CA 2000165 CA2000165 CA 2000165 CA 2000165 A CA2000165 A CA 2000165A CA 2000165 A1 CA2000165 A1 CA 2000165A1
- Authority
- CA
- Canada
- Prior art keywords
- co2me
- ipr
- oet
- tbu
- ocf3
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
TITLE
N-SULFENYLATED AND N-ACYLATED PYRAZOLINES
Abstract of the Disclosure N-sulfenylated and N-acylated pyrazoline arthropodicides, compositions containing them and methods for controlling arthropods by applying compounds of the invention to them or to their environment. The pyrazolines are selected from those of Formulae I to III wherein R1, R2, R3, Q, A, B, J, K, Y, m, n and p are as defined in the text:
I II
N-SULFENYLATED AND N-ACYLATED PYRAZOLINES
Abstract of the Disclosure N-sulfenylated and N-acylated pyrazoline arthropodicides, compositions containing them and methods for controlling arthropods by applying compounds of the invention to them or to their environment. The pyrazolines are selected from those of Formulae I to III wherein R1, R2, R3, Q, A, B, J, K, Y, m, n and p are as defined in the text:
I II
Description
2~QQ~65 ~IT~E :
N-SULFE_YLA~ N-ACYLATED PY~AZO~INES-ELackaround of the Invention -The following publications disclose pyrazolines: .
V.S. 4,070,365 EPA 21,506 .
. 10 U.S. 4,156,007 EPA 5B,424 U.S. 4,174,393 EPA 65,334 U.S. 4,663,341 EPA 113,213 Wo 88/05046 EPA 153,127 wo 88/07994 EPA 286,346 ; 15 wo 89/00562 EPA 300,692 Grosscurt et al., -J. Aa~ic. Food Chem., ; Vol. 27, No. 2 (1979).
~ 20 This application is a cognate of U.S. applica-:.`: tions 07/249, 881 and 07/304,011.
mE~y of the InventiQn This invention pertains to compounds of Formulae l~ 25 I, II and III, including all geometric and stereo-.~ isomers, agriculturally suitable salts thereof, . compositions containing them and their use as arthropodicides in agricultural and home uses.
Hereafter, the compounds, isomers and salts are . 30 referred to as compound(s) for the sake of simplicity. The compounds are:
. . .
','1 ~' , ' :,':
. 35 . .:
.~ . ''~.
... .
,,~ . i .
~ ' .. , -- . . . ~ . . : . ... . .
2110Q~6S
-:
(Rz~n~kR3)P ~ ~R ~ .
N~N /~IXH
o~f ~N~ --f ~N~
~; 15 . II
'' , .
.
I I I
' 30 .- wherein A is a 1, 2 or 3-atom bridge comprising 0 to 3 ~ .
carbon atoms, 0 to 1 o~ygen atoms, NR6, or S(O)q, wherein each carbon individually can /!~
be substituted with 1 to 2 substituents selected from 1 to 2 halogen, Cl to C6 alkyl, ~ .
. :
'.
- . : ::, - . . . .
2~ 65 ~ 3 . .
C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W and one of the carbon atoms can be combined into the group C(O) or C(S);
is H, Cl to C6 alkyl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 - to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4Rs, C(S)NR4Rs, C(S)R4, C(S)SR4, phenyl, phenyl substituted by (R14)p, benzyl, .
~: or benzyl substituted with 1 to 3 , substituents independently selected from W; .
J is H, Cl to C4 alkyl or phenyl optionally substituted with W;
~- ~ is H or CH3;
- q is 0, 1 or 2;
Rl, R2, R3 and R14 are independently selected .^ from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, .~ 25 S(O)R4, S(O)2R4, OC(O)R4, OS¦O)2R4, CO2R4, C(O)R4, C(O)NR4Rs~ S()2NR4R5~ NR4R5~
NRsC(O)R4, OC(O)NHR4, NR5C(O)NHR~ and ~ NR5S(O)2R4; or when m, n or p is 2, Rl, R2, : R3 or R14 can independently be taken together ; 30 as OCH2O, OCH2CH2O or CH2CH2O, to form a 5 or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups; :
R4 is selected from H, Cl to C6 al~yl, C3 to C6 . 35 cycloalkyl, C3 to C8 alko~ycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, Cl to C
.,' ` ' "
, :
,; ..
,' '" ' ' ' ' ' ` ' ' "' "' ' ` " ' '`" " ` ' . ' ' ~.'` ~ ' ' ` ' 2~0Q~65 : 4 haloalkyl, C3 to C6 haloalkenyl, Cl to C6 - alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally : substituted with W; or R4 and P~5 can be taken together as (CH2)4, (CH2)5 or CH2cH2ocH2cH2 R5 is selected from H, Cl to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or Cl to C4 halo-alkyl;
m, n and p are independently 1 to 3;
~: W is halogen, CN, NO2, Cl to C2 alkyl, Cl to C2 :. haloalkyl, Cl to C2 alkoxy, Cl to C? halo-:~. 15 alkoxy, Cl to C2 alkylthio, Cl to C2 halo-.i alkylthio, Cl to C2 alkylsulfonyl or Cl to C2 haloalkylsulfonyl;
:- ~6 is H, Cl to C4 alkyl, Cl to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl ~ 20 optionally substituted with W or benzyl optionally substituted with W;
.~ R7 is H, Cl to C4 alkyl, C2 to C4 alkenyl, C2 to C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 .- alkoxycarbonyl or Cl-C4 alkylsulfonyl;
Q is SX, C2 to C22 alko~ycarbonyl, C2 to C22 . haloalkoxycarbonyl, C7 to C15 pheno~ycarbonyl optionally substitu'sed with 1 to 3 substi- !:
.
tuents selected f rom W; C7 to C15 phenyl carbonyl optionally substituted with 1 to 3 substituents independently selected f rom W;
C2 to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben-zylosycarbonyl optionally substituted with 1 to 3 subs'cituents independently selected from .
... .
,' 7 ' ' ' . . . ' . ~ , ~ . ' ' . - ~
2~0C~.65 w; when Q is other than SX, R3 is other than C2R~ C(O)R4, SO2NR3R4 or CONR4R5;
is C5 to C22 alkyl, C2 to C22 haloalkyl, C5 to Cz2 alkoxyalkyl, C4 to C22 alkoxyalkoxyalkyl, C5 to C12 alkylthio, C5 to C12 haloalkylthio, : C5 to C22 alkylcarbonyl, C5 to C22 ~ haloalkylcarbonyl, C5 to C22 alkoxycarbonyl, 10 C3 to C22 haloalkoxycarbonyl, or SX;
Z is C7 to C22 alkyl, C2 to C22 haloalkyl, C7 to C22 alko~yal~yl, C4 to C22 alko~yalkoxyalkyl, C7 to C12 alkylthio, C7 to C12 haloalkylthio, C7 to C22 alkylcarbonyl, C7 to C22 t.
: 15 haloalkylcarbonyl, C7 to C22 alko~ycarbonyl, C3 to C22 haloalkoxycarbonyl or SX;
~Y Rlo 1~Y Rll .
X is NR8CRg~ NRgS(O)aRg, NR8P~y,R 8 ~Rlo CR9 PI~R10 NR8R12 or SR10 2 5 ~R 11 X7 ~8 . R8 and R12 are independently Cl to C6 alkyl, . Cl to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally :.
substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents independently selected from W, phenethyl optionally substituted by 1 to 2 substituents independently selected from W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 to .. ,:
:~ , . :
., . , . -.
., . .. . . . . - : . .. .
- .
Zl~Q~6~
C8 alkoxycarbonylal)cyl, C4 to C8 dialkylaminocarbonylalkyl; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)20(CH2)2~
Rg is F, Cl to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalko~y, C2 to C8 dialkylamino, Cl to C6 haloalkyl, phenyl or phenoxy either : 10 optionally substituted by 1 to 2 substituents independently selected from W; Cl to C22 alkoxy, Cl to C4 alkoxy substituted by cyano, nitro, C2 to C4 alko~y, C4 to C~ alko~y~lkoxy, Cl to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or R9 is morpholino, piperidino or -.
pyrrolidino, l-naphthoxy, 2,2-dimethyl-2,3-. dihydrobenzofuranoxy-7 or ON~C(CH3)SCH3;
: Rlo and Rll are independently Cl to C4 alky.l, ! ;
C2 to C4 haloalkyl or phenyl optionally substituted by 1 to 2 substituents independently selected from W; or Rlo and Rll . -: can be taken together as (CH2)2, (CH2)3 or CH2C(CH3)2cH2;
i 25 Y~ is S or O; and s~ a is 0 to 2.
~.
Preferred compounds A are those of Formula I, II ::
i or III wherein:
Rl, R2, R3 and R14 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(0)2R4 or ; NR4R5, or when m, n or p is 2;
Rl, R2, R3 or R14 can be taken together as OC~20, - OCH2CH20 or CH2CH20, each of which can be :. 35 substituted with 1 to 4 halogen atoms or 1 to 2 ; methyl groups;
~ .
~
. . , I .
., .
zn~6s R4 is Cl to C2 alkyl, C3 to Cq alkenyl, Cl to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen:
R5 is H or Cl to C2 alkyl;
Q is S~, CHO, C2 to C6 alkoxycarbonyl, C2 - to C6 haloalko~ycarbonyl, C2 to C~ alkyl-carbonyl, C2 to C4 haloalkylcarbonyl, 10 C7 to C10 phenoxycarbonyl, C7 to C10 phenylcarbonyl or C8 to C10 benzyloxy-carbonyl each pheno~y, phenyl Dr benzyl-o~y group optionally substituted with 1 to 2 substituents selected from W;
X is Xl, X2, X3, X4 or Xs;
R8 and R12 are independently Cl to C6 alkyl, Cl to C6 haloalkyl, C5 to C6 cycloalkyl, . C3 to C8 alkoxycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally . 20 independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(cH2)2;
Rlo and Rll are independently Cl to C3 alkyl ` or phenyl; :
a is 2;
Formula III is ~
~R-3)9 ( R2) n~ ( R2) n~
N--N N~N
.
;, r~ .
2(~ 6S
(Rz),{~: ~Rz)"~ or .
lS
' ' X
2 0 ( R,) n~
N ~N
i ` .
`s 25 .' ~ .
, X' is O or S;
t is 0, 1 or 2; ~ ~
V is 0, S(O)g, or NR6; ~ ~ .
Z' is O or NR6;
R13 is H, halogen, Cl to C6 alkyl, C2 to C4 alkosycarbonyl~ phenyl or phenyl substi- :
tuted by 1 to 3 substituents independently :~
, selected from W; and ; g 18 O, 1 or 2.
; ! ' ~. '.
' . .. . ' ' . ' .. - . . ' ':.: ` , : ',: , . . :
,' . ' . . ' . : ' . ., . . ~ : , . . ' ' , ' ' ' , . ' , .' ' ' . ! .
Zn~Q'L~5 Preferred compounds B are compounds A wherein:
Rl is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, 5 . OCF2CF2H, CF3 or when m is 2 then Rl may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring;
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
: R3 and R14 are independently R2 or CO2R4;
Q is SX, C2 to C4 alko~ycarbonyl, C2 to C4 alkylcarbonyl, C7 to CB phenylcarbonyl or CHO;
: 1~ X is Xl, X2 or X3;
` R8 is Cl to C4 alkyl, CF3, cyclohexyl, phenyl optionally substituted with W or benzyl optionally substituted by W;
R9 is F, Cl to C22 alkyl, Cl to C6 haloalkyl, phenyl or phenoxy optionally substituted by W; Cl to C22 alkoxy, dimethylamino or Cl to C4 alkoxy substituted with NO2, C2 to C4 alkoxy or 1 to 6 halogens;
.; m, n or p are independently 1 to 2 and one , .
'. 25 substituent is in the 4-position and B is H, Cl-C4 alkyl, CO2R4, C(ojR4 or phenyl ` optionally substituted by (R14)p.
.:
Preferred compounds C are preferred compounds B
wherein:
X is Xl;
:.~ R8 is Cl to C4 alkyl;
Rg is Cl to C22 alko~y;
Formula III is III-l or III-2;
V is O or CH2; :
t is l; and R13 is H.
,.:
: ~ . . , . . - .. .. - . :. . : . . . - .
2~1~Q~6S
Preferred compounds D are preferred compounds wherein:
X is X2;
R8 is Cl to C4 alkyl or phenyl optionally substituted with CH3 or Cl; and Rg is Cl to C6 alkyl, Cl to C6 haloalkyl, dimethylamino or phenyl optionally substituted with CH3 or Cl.
;
Preferred compounds E are preferred compounds C
: of Formula I.
Preferred compounds F are preferred compounds B
of Formula II.
Preferred compounds G are preferred compounds B
of Formula III.
Specifically preferred are the compounds:
20 H. methyl 3,4-di-(4-chlorophenyl)-1-t[N-~: [[(ethoxycarbonyl)(l-methylethyl)-amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro- ~ ~ .
lH-pyrazole of preferred E;
2S I. N-acetyl-3,4-bis(4-chloropheny)-; 4,5-dihydro-N-[4-(trifluoromethyl) phenyl]-lH-pyrazole-l-carboxamide of .preferred F; and : J. methyl 7-chloro-3,3a,4,5-tetrahydro- :.
2-[EN-[[N-methyl-N-[octadecylo~y)-carbonyl~amino]thiol-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl]-2H-benz-[g]indazole-3a-carbo~ylate o preferred G.
','' -.
', ; , .. . . . . . . . . . . .. . .. . . .. . . . .
2(~ 'L65 Details of the Invention Compounds of Formulae I, II and III can be 5 prepared by the reaction of a pyrazoline compound of -Formula V, VI or VII with a sulfenyl halide of : Formula IV.
': :
(R2)n~
--N~ XSY III
(R~)m ~ NH
V IV
.s~
. ..
. ~R,)~ R3)p .` / I XSY ' I
.. N~N~
o~N~ R1 ) m H
Vl IV
: :
` 35 .,.
: ' '-.
' ' ., " .:
-: : . . : :: : :, . . . . .
~:~0~!~6S
( R2 ~n ~ R3~ p 1 N~H Y . I I
H~( VII IV
wherein ~.
Y in Formula IV represents a halogen such as chloro, bromo, or iodo.
~j :
The treatment of V, VI or VII with IV is carried out by mixing the two reagents in the presence of a base and a solvent. Suitable bases are the tertiary -25 amines such as triethylamine or pyridine. Alkali metal bases such as sodium hydride or potassium tert-butoxide or organo lithium bases such as aryl or alkyllithium also can be utilized.
Suitable solvents include methylene chloride, 30 tetrahydrofuran or ether. In some cases, the base can :
also be used as the solvent, e.g., pyridine. In most cases, it is desirable to mi~ compounds o~ Formula v, VI or VII and the desired base at a low temperature of about 5C to -70C which is held at this temperature ~ ' - 3s during treatment with the appropriate amount of compounds of Formula IV. The mi~ture is then warmed '','~ "
" .
.
.
- : . ., . . : . . :. . .. -2C~Q~65 to room temperature to complete the reaction.
Generally, it is desirable to employ a moderate stoichio~etric excess, up to 10% of the base and compounds of Formula IV relative to compounds of Formula V, VI or VII. Water should be e~cluded from the reaction mixture by using anhydrous reagents and conducting the treatment in a nitrogen atmosphere.
The product is isolated and purified by conventional techniques as demonstrated in E~ample 1. The pyra-zoline precursors of Formula V, VI, and VII are compounds that can be prepared by methods known to those skilled in the art. The methods of pyrazoline synthesis have been recently reviewed by El-Rayyes and Al-Awadi in "Synthesis" page 1028 to 1042, November `~ 1985.
Compounds of Formula V wherein B-H can be prepared by the following sequence of reactions as shown in Scheme 1.
SCHEME I
`: :
Rx A
. . .
(R~n ~ ~ ~N-NH~ ~
VIII IX
~.
~' : ' :, . .. ~ . , - , - , .
2~QQ~,S
': :
, IX ~ (R~)i~NCO -- V (B=H) `~
. :,' .
. .
:' ., .
In another embodiment, certain compounds of ;` 15 Formula V wherein B is other than H can be prepared :-directly from compounds of Formula V wherein B is H
by further treatment with a base and the appropriate type of electrophile as illustrated by Scheme 2~ :
S~HEME 2 . 1. Base ', V -----~ V
,......................................................................... . .
is H) 2. electrophile ~B is other than H, r~3i phenyl, or substi-tuted phenyl) ,:
Compounds of Formula V where B is also phenyl ~l;.
~ or substituted phenyl can be prepared by reaction of a .. i substituted ketone of Formula X with hydrazine as .i shown in Scheme 3.
. :
,,`, i: :
.~ .
N-SULFE_YLA~ N-ACYLATED PY~AZO~INES-ELackaround of the Invention -The following publications disclose pyrazolines: .
V.S. 4,070,365 EPA 21,506 .
. 10 U.S. 4,156,007 EPA 5B,424 U.S. 4,174,393 EPA 65,334 U.S. 4,663,341 EPA 113,213 Wo 88/05046 EPA 153,127 wo 88/07994 EPA 286,346 ; 15 wo 89/00562 EPA 300,692 Grosscurt et al., -J. Aa~ic. Food Chem., ; Vol. 27, No. 2 (1979).
~ 20 This application is a cognate of U.S. applica-:.`: tions 07/249, 881 and 07/304,011.
mE~y of the InventiQn This invention pertains to compounds of Formulae l~ 25 I, II and III, including all geometric and stereo-.~ isomers, agriculturally suitable salts thereof, . compositions containing them and their use as arthropodicides in agricultural and home uses.
Hereafter, the compounds, isomers and salts are . 30 referred to as compound(s) for the sake of simplicity. The compounds are:
. . .
','1 ~' , ' :,':
. 35 . .:
.~ . ''~.
... .
,,~ . i .
~ ' .. , -- . . . ~ . . : . ... . .
2110Q~6S
-:
(Rz~n~kR3)P ~ ~R ~ .
N~N /~IXH
o~f ~N~ --f ~N~
~; 15 . II
'' , .
.
I I I
' 30 .- wherein A is a 1, 2 or 3-atom bridge comprising 0 to 3 ~ .
carbon atoms, 0 to 1 o~ygen atoms, NR6, or S(O)q, wherein each carbon individually can /!~
be substituted with 1 to 2 substituents selected from 1 to 2 halogen, Cl to C6 alkyl, ~ .
. :
'.
- . : ::, - . . . .
2~ 65 ~ 3 . .
C2 to C4 alkoxycarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W and one of the carbon atoms can be combined into the group C(O) or C(S);
is H, Cl to C6 alkyl, C4 to C7 cycloalkyl alkyl, C3 to C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3; Cl to C6 haloalkyl, C2 to C6 alkenyl, C2 - to C6 haloalkenyl, C2 to C6 alkynyl, OR7, C2 to C6 alkoxyalkyl, C2 to C6 cyanoalkyl, C3 to C8 alkoxycarbonylalkyl, CO2R4, C(O)R4, C(O)NR4Rs, C(S)NR4Rs, C(S)R4, C(S)SR4, phenyl, phenyl substituted by (R14)p, benzyl, .
~: or benzyl substituted with 1 to 3 , substituents independently selected from W; .
J is H, Cl to C4 alkyl or phenyl optionally substituted with W;
~- ~ is H or CH3;
- q is 0, 1 or 2;
Rl, R2, R3 and R14 are independently selected .^ from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, .~ 25 S(O)R4, S(O)2R4, OC(O)R4, OS¦O)2R4, CO2R4, C(O)R4, C(O)NR4Rs~ S()2NR4R5~ NR4R5~
NRsC(O)R4, OC(O)NHR4, NR5C(O)NHR~ and ~ NR5S(O)2R4; or when m, n or p is 2, Rl, R2, : R3 or R14 can independently be taken together ; 30 as OCH2O, OCH2CH2O or CH2CH2O, to form a 5 or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups; :
R4 is selected from H, Cl to C6 al~yl, C3 to C6 . 35 cycloalkyl, C3 to C8 alko~ycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, Cl to C
.,' ` ' "
, :
,; ..
,' '" ' ' ' ' ' ` ' ' "' "' ' ` " ' '`" " ` ' . ' ' ~.'` ~ ' ' ` ' 2~0Q~65 : 4 haloalkyl, C3 to C6 haloalkenyl, Cl to C6 - alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally : substituted with W; or R4 and P~5 can be taken together as (CH2)4, (CH2)5 or CH2cH2ocH2cH2 R5 is selected from H, Cl to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or Cl to C4 halo-alkyl;
m, n and p are independently 1 to 3;
~: W is halogen, CN, NO2, Cl to C2 alkyl, Cl to C2 :. haloalkyl, Cl to C2 alkoxy, Cl to C? halo-:~. 15 alkoxy, Cl to C2 alkylthio, Cl to C2 halo-.i alkylthio, Cl to C2 alkylsulfonyl or Cl to C2 haloalkylsulfonyl;
:- ~6 is H, Cl to C4 alkyl, Cl to C4 haloalkyl, C2 to C4 alkenyl, C2 to C4 haloalkenyl, phenyl ~ 20 optionally substituted with W or benzyl optionally substituted with W;
.~ R7 is H, Cl to C4 alkyl, C2 to C4 alkenyl, C2 to C4 alkynyl, C2 to C4 alkylcarbonyl, C2 to C4 .- alkoxycarbonyl or Cl-C4 alkylsulfonyl;
Q is SX, C2 to C22 alko~ycarbonyl, C2 to C22 . haloalkoxycarbonyl, C7 to C15 pheno~ycarbonyl optionally substitu'sed with 1 to 3 substi- !:
.
tuents selected f rom W; C7 to C15 phenyl carbonyl optionally substituted with 1 to 3 substituents independently selected f rom W;
C2 to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben-zylosycarbonyl optionally substituted with 1 to 3 subs'cituents independently selected from .
... .
,' 7 ' ' ' . . . ' . ~ , ~ . ' ' . - ~
2~0C~.65 w; when Q is other than SX, R3 is other than C2R~ C(O)R4, SO2NR3R4 or CONR4R5;
is C5 to C22 alkyl, C2 to C22 haloalkyl, C5 to Cz2 alkoxyalkyl, C4 to C22 alkoxyalkoxyalkyl, C5 to C12 alkylthio, C5 to C12 haloalkylthio, : C5 to C22 alkylcarbonyl, C5 to C22 ~ haloalkylcarbonyl, C5 to C22 alkoxycarbonyl, 10 C3 to C22 haloalkoxycarbonyl, or SX;
Z is C7 to C22 alkyl, C2 to C22 haloalkyl, C7 to C22 alko~yal~yl, C4 to C22 alko~yalkoxyalkyl, C7 to C12 alkylthio, C7 to C12 haloalkylthio, C7 to C22 alkylcarbonyl, C7 to C22 t.
: 15 haloalkylcarbonyl, C7 to C22 alko~ycarbonyl, C3 to C22 haloalkoxycarbonyl or SX;
~Y Rlo 1~Y Rll .
X is NR8CRg~ NRgS(O)aRg, NR8P~y,R 8 ~Rlo CR9 PI~R10 NR8R12 or SR10 2 5 ~R 11 X7 ~8 . R8 and R12 are independently Cl to C6 alkyl, . Cl to C6 haloalkyl, C3 to C6 cycloalkyl, C4 to C7 cycloalkylalkyl, phenyl optionally :.
substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents independently selected from W, phenethyl optionally substituted by 1 to 2 substituents independently selected from W, C2 to C6 cyanoalkyl, C2 to C6 alkoxyalkyl, C3 to .. ,:
:~ , . :
., . , . -.
., . .. . . . . - : . .. .
- .
Zl~Q~6~
C8 alkoxycarbonylal)cyl, C4 to C8 dialkylaminocarbonylalkyl; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)20(CH2)2~
Rg is F, Cl to C22 alkyl, C3 to C6 cycloalkyl, C3 to C6 cycloalko~y, C2 to C8 dialkylamino, Cl to C6 haloalkyl, phenyl or phenoxy either : 10 optionally substituted by 1 to 2 substituents independently selected from W; Cl to C22 alkoxy, Cl to C4 alkoxy substituted by cyano, nitro, C2 to C4 alko~y, C4 to C~ alko~y~lkoxy, Cl to C2 alkylthio, C2 to C3 alkoxycarbonyl, C3 to C5 dialkylaminocarbonyl, phenyl or 1 to 6 halogens; or R9 is morpholino, piperidino or -.
pyrrolidino, l-naphthoxy, 2,2-dimethyl-2,3-. dihydrobenzofuranoxy-7 or ON~C(CH3)SCH3;
: Rlo and Rll are independently Cl to C4 alky.l, ! ;
C2 to C4 haloalkyl or phenyl optionally substituted by 1 to 2 substituents independently selected from W; or Rlo and Rll . -: can be taken together as (CH2)2, (CH2)3 or CH2C(CH3)2cH2;
i 25 Y~ is S or O; and s~ a is 0 to 2.
~.
Preferred compounds A are those of Formula I, II ::
i or III wherein:
Rl, R2, R3 and R14 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(0)2R4 or ; NR4R5, or when m, n or p is 2;
Rl, R2, R3 or R14 can be taken together as OC~20, - OCH2CH20 or CH2CH20, each of which can be :. 35 substituted with 1 to 4 halogen atoms or 1 to 2 ; methyl groups;
~ .
~
. . , I .
., .
zn~6s R4 is Cl to C2 alkyl, C3 to Cq alkenyl, Cl to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen:
R5 is H or Cl to C2 alkyl;
Q is S~, CHO, C2 to C6 alkoxycarbonyl, C2 - to C6 haloalko~ycarbonyl, C2 to C~ alkyl-carbonyl, C2 to C4 haloalkylcarbonyl, 10 C7 to C10 phenoxycarbonyl, C7 to C10 phenylcarbonyl or C8 to C10 benzyloxy-carbonyl each pheno~y, phenyl Dr benzyl-o~y group optionally substituted with 1 to 2 substituents selected from W;
X is Xl, X2, X3, X4 or Xs;
R8 and R12 are independently Cl to C6 alkyl, Cl to C6 haloalkyl, C5 to C6 cycloalkyl, . C3 to C8 alkoxycarbonylalkyl, phenyl, benzyl or phenethyl, each optionally . 20 independently substituted with W; or R8 and R12 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(cH2)2;
Rlo and Rll are independently Cl to C3 alkyl ` or phenyl; :
a is 2;
Formula III is ~
~R-3)9 ( R2) n~ ( R2) n~
N--N N~N
.
;, r~ .
2(~ 6S
(Rz),{~: ~Rz)"~ or .
lS
' ' X
2 0 ( R,) n~
N ~N
i ` .
`s 25 .' ~ .
, X' is O or S;
t is 0, 1 or 2; ~ ~
V is 0, S(O)g, or NR6; ~ ~ .
Z' is O or NR6;
R13 is H, halogen, Cl to C6 alkyl, C2 to C4 alkosycarbonyl~ phenyl or phenyl substi- :
tuted by 1 to 3 substituents independently :~
, selected from W; and ; g 18 O, 1 or 2.
; ! ' ~. '.
' . .. . ' ' . ' .. - . . ' ':.: ` , : ',: , . . :
,' . ' . . ' . : ' . ., . . ~ : , . . ' ' , ' ' ' , . ' , .' ' ' . ! .
Zn~Q'L~5 Preferred compounds B are compounds A wherein:
Rl is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, 5 . OCF2CF2H, CF3 or when m is 2 then Rl may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring;
R2 is H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
: R3 and R14 are independently R2 or CO2R4;
Q is SX, C2 to C4 alko~ycarbonyl, C2 to C4 alkylcarbonyl, C7 to CB phenylcarbonyl or CHO;
: 1~ X is Xl, X2 or X3;
` R8 is Cl to C4 alkyl, CF3, cyclohexyl, phenyl optionally substituted with W or benzyl optionally substituted by W;
R9 is F, Cl to C22 alkyl, Cl to C6 haloalkyl, phenyl or phenoxy optionally substituted by W; Cl to C22 alkoxy, dimethylamino or Cl to C4 alkoxy substituted with NO2, C2 to C4 alkoxy or 1 to 6 halogens;
.; m, n or p are independently 1 to 2 and one , .
'. 25 substituent is in the 4-position and B is H, Cl-C4 alkyl, CO2R4, C(ojR4 or phenyl ` optionally substituted by (R14)p.
.:
Preferred compounds C are preferred compounds B
wherein:
X is Xl;
:.~ R8 is Cl to C4 alkyl;
Rg is Cl to C22 alko~y;
Formula III is III-l or III-2;
V is O or CH2; :
t is l; and R13 is H.
,.:
: ~ . . , . . - .. .. - . :. . : . . . - .
2~1~Q~6S
Preferred compounds D are preferred compounds wherein:
X is X2;
R8 is Cl to C4 alkyl or phenyl optionally substituted with CH3 or Cl; and Rg is Cl to C6 alkyl, Cl to C6 haloalkyl, dimethylamino or phenyl optionally substituted with CH3 or Cl.
;
Preferred compounds E are preferred compounds C
: of Formula I.
Preferred compounds F are preferred compounds B
of Formula II.
Preferred compounds G are preferred compounds B
of Formula III.
Specifically preferred are the compounds:
20 H. methyl 3,4-di-(4-chlorophenyl)-1-t[N-~: [[(ethoxycarbonyl)(l-methylethyl)-amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro- ~ ~ .
lH-pyrazole of preferred E;
2S I. N-acetyl-3,4-bis(4-chloropheny)-; 4,5-dihydro-N-[4-(trifluoromethyl) phenyl]-lH-pyrazole-l-carboxamide of .preferred F; and : J. methyl 7-chloro-3,3a,4,5-tetrahydro- :.
2-[EN-[[N-methyl-N-[octadecylo~y)-carbonyl~amino]thiol-N-[4-(trifluoro-methyl)-phenyl]amino]carbonyl]-2H-benz-[g]indazole-3a-carbo~ylate o preferred G.
','' -.
', ; , .. . . . . . . . . . . .. . .. . . .. . . . .
2(~ 'L65 Details of the Invention Compounds of Formulae I, II and III can be 5 prepared by the reaction of a pyrazoline compound of -Formula V, VI or VII with a sulfenyl halide of : Formula IV.
': :
(R2)n~
--N~ XSY III
(R~)m ~ NH
V IV
.s~
. ..
. ~R,)~ R3)p .` / I XSY ' I
.. N~N~
o~N~ R1 ) m H
Vl IV
: :
` 35 .,.
: ' '-.
' ' ., " .:
-: : . . : :: : :, . . . . .
~:~0~!~6S
( R2 ~n ~ R3~ p 1 N~H Y . I I
H~( VII IV
wherein ~.
Y in Formula IV represents a halogen such as chloro, bromo, or iodo.
~j :
The treatment of V, VI or VII with IV is carried out by mixing the two reagents in the presence of a base and a solvent. Suitable bases are the tertiary -25 amines such as triethylamine or pyridine. Alkali metal bases such as sodium hydride or potassium tert-butoxide or organo lithium bases such as aryl or alkyllithium also can be utilized.
Suitable solvents include methylene chloride, 30 tetrahydrofuran or ether. In some cases, the base can :
also be used as the solvent, e.g., pyridine. In most cases, it is desirable to mi~ compounds o~ Formula v, VI or VII and the desired base at a low temperature of about 5C to -70C which is held at this temperature ~ ' - 3s during treatment with the appropriate amount of compounds of Formula IV. The mi~ture is then warmed '','~ "
" .
.
.
- : . ., . . : . . :. . .. -2C~Q~65 to room temperature to complete the reaction.
Generally, it is desirable to employ a moderate stoichio~etric excess, up to 10% of the base and compounds of Formula IV relative to compounds of Formula V, VI or VII. Water should be e~cluded from the reaction mixture by using anhydrous reagents and conducting the treatment in a nitrogen atmosphere.
The product is isolated and purified by conventional techniques as demonstrated in E~ample 1. The pyra-zoline precursors of Formula V, VI, and VII are compounds that can be prepared by methods known to those skilled in the art. The methods of pyrazoline synthesis have been recently reviewed by El-Rayyes and Al-Awadi in "Synthesis" page 1028 to 1042, November `~ 1985.
Compounds of Formula V wherein B-H can be prepared by the following sequence of reactions as shown in Scheme 1.
SCHEME I
`: :
Rx A
. . .
(R~n ~ ~ ~N-NH~ ~
VIII IX
~.
~' : ' :, . .. ~ . , - , - , .
2~QQ~,S
': :
, IX ~ (R~)i~NCO -- V (B=H) `~
. :,' .
. .
:' ., .
In another embodiment, certain compounds of ;` 15 Formula V wherein B is other than H can be prepared :-directly from compounds of Formula V wherein B is H
by further treatment with a base and the appropriate type of electrophile as illustrated by Scheme 2~ :
S~HEME 2 . 1. Base ', V -----~ V
,......................................................................... . .
is H) 2. electrophile ~B is other than H, r~3i phenyl, or substi-tuted phenyl) ,:
Compounds of Formula V where B is also phenyl ~l;.
~ or substituted phenyl can be prepared by reaction of a .. i substituted ketone of Formula X with hydrazine as .i shown in Scheme 3.
. :
,,`, i: :
.~ .
3 5 .:
:' ' .
.,~ , .
.', . ~
.' ' '~'.
.,', '' ~:.~.
.. .. - : , , . .. ~ .
2~1()Q~65 ~Ç~E 3 RX E~
(R~n~l~-X ~Rj~D~\_~H
X XI
, .
(X = Cl, ~r, tosyl or other l~avlng groups) ~ '~
., ' ' ' .
-~ 20 ' ":
XI ~ ~ R1 ) m~t~CO -- V
:~ - 25 (13 19 phçlnyl or ~ubstltuted phenyl) :. ' ' ;
For compounds of Formula.VI, Gro~scurt et al., have published the synthesis of 3,9-diphenyl-1-phenyl-; carbamoyl-2-pyrazolines in Journal of Agricultural :~
and Food Chemistry, 27:406-409 (1979). Similar methods of synthesis are also presented in U.S.
:' ' .
.,~ , .
.', . ~
.' ' '~'.
.,', '' ~:.~.
.. .. - : , , . .. ~ .
2~1()Q~65 ~Ç~E 3 RX E~
(R~n~l~-X ~Rj~D~\_~H
X XI
, .
(X = Cl, ~r, tosyl or other l~avlng groups) ~ '~
., ' ' ' .
-~ 20 ' ":
XI ~ ~ R1 ) m~t~CO -- V
:~ - 25 (13 19 phçlnyl or ~ubstltuted phenyl) :. ' ' ;
For compounds of Formula.VI, Gro~scurt et al., have published the synthesis of 3,9-diphenyl-1-phenyl-; carbamoyl-2-pyrazolines in Journal of Agricultural :~
and Food Chemistry, 27:406-409 (1979). Similar methods of synthesis are also presented in U.S.
4,633,341. Compounds of Formula VII have been prepared using procedures indicated in PCT
WO 88/OS046. .
. .
;,'.
, , , , ~, . , , " ., .. - . , , . . , . - . . . ~ .
2(~ 65 ~, ~..
Sulfenyl halides of the type XSY (Formula IV) wherein X and Y are as specified in this disclosure are known in the literature. A review article by Kule in Synthesis, 561, ~1970) describes the chemistry and preparation of the majority of sulfenyl halides utilized in this invention. The synthesis of N-chlorosulfenylcarbamates was described in U.S.
3,843,689. Other sulfenyl halides can be prepared by the general procedures described in these literature e~amples or obvious modifications thereof.
Compounds of Formula I (Q is other than SX) are synthesized from compounds of Formula VI.
15 Reaction of compounds of Formula VI in the presence :
of an acid acceptor with electrophilic - carbonyl-containing reagents results in substitution on nitrogen. Strong bases known to deprotonate ureas such as potassium t-butoxide, potassium hydride and sodium hydride are the preferred acid acceptors in the process. Suitable electrophiles include, but are ; not restricted to , acyl halides, acid anhydrides, carbonates, and chloroformates. The reaction sequence is normally run in the temperature range of -10 to 25C, but can be run at temperatures as high ` as 110C or as low as -50C in certain cases.
Solvents which are not deprotonated under the conditions of the reaction such as tetrahydrofuran, dimethylformamide, dimethoxyethane, and diethyl ether -~
-': ,; -, .
, . ' . ~ ! , . . . .
X~QC~65 are preferred. The electrophiles used in this process are well known to those skilled in the art and are generally commercially available.
Acïd Acceptor VI ~ QX
.. 10 wherein: ;
; QX is selected from acyl halides, chloroformates a~d acid anhydrides.
The following Examples illustrate the invention.
;~ . , ' Example_1 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)pheny]-N-[N'-(l-methyl-ethyl)-N'-(etho~ycarbonyl)aminosulfenyl]-2H-benz~alindazole-2-carbo~amide :
Step A: 3,3a,4,5-Tetrahydro-N-[4-~trifluoromethyl)-phenyl]-2H-benz[g]indazole-2-carboxamide A mixture of 10.0 9 of -tetralone, 2.0 9 of paraformaldehyde, 6.5 9 of dimethylamine hydrochloride and 1.75 ml of conc. HCl in 20 ml of ethanol was heated at reflux for 24 h, cooled to room temperature and then partitioned between ether and . water. The aqueous extracts-were made basic with lN
aqueous NaOH and e~tracted with ether. The ether extracts were dried over magnesium sulfate and ~-concentrated to 12.3 g of a yellow oil. The residual oil was dissolved in 40 ml of n-propyl alcohol, combined with 6.7 ml of hydrazine hydra~e and heated .' ~,: ..
- v . .
" . :~ . . . : : : ~ : . . :: ~ : :
Z(?Q~65 at reflu~ for 1 h. The reaction mixture was then concentrated under vacuum, partitioned between 5%
aqueous NaHCO3 and methylene chloride and dried over magnesium sulfate. To the methylene chloride :
extracts were added 12.5 9 of 4-trifluoro-methylphenyl isocyanate and the mixture was then re-fluxed o~e hour, cooled to room temperature and con-centrated to 26.1 9 of a brown oil. Chromatography on silica gel followed by trituration with ether afforded 11.78 g of the title compound as a tan powder, m.p. 149-151C.
lH NMR (CDC13), ~ 1.9 (m,lH), 2.4 (m,lH), 3.0 (m, - 15 2H), 3.5 (m,2H), 4.4 (m,lH), 7.3 (m,3H), 7.58 (d,2H), 7.65 (d,2H), 8.0 (d,2H), 8.3 (bs,lH).
;.' Step B: 3,3a,4,5-tetrahydro-3a-metho~ycarbonyl-N-[4'-(trifluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide ,, :
; To a solution of 0.9 ml of diisopropylamine in 10 ml of THF, at -78C, was added 2.3 ml of 2.5 M
n-butyl lithium in hexane and the mi~ture was stirred -25 for 5 mins. To this solution was added a solution of 1.0 9 of the title compound of Step A in 5 ml of THF. The reaction was warmed to 0C, recooled to -78C and then 0.75 ml of methyl chloroformate was added. The reaction mixture was then stirred for 24 ; 30 h, with gradual warming to room temperature, quenched with 0.5 ml of glacial acetic acid, and poured into a 5% solution of aqueous NaHCO3. The mi~ture was ; extracted with chloroform, dried over magnesium sulfate and concentrated. Chromatography on silica 35 gel with 30% ethyl acetate he~ane afforded 0.25 9 of the title compound, m.p. 177 to 180C.
. . .
"' :- ' ' ' ' , ' . ' ,~
:
2~ 65 :
lH NMR (CDC13), 6 2.1 (m,lH), 2.7 (m,lH), 3.0 (m,2H), 3.71 (s,3H), 3.76 (d,lH), 4.5~ (d,lH), 7.3 (m,3H), 7.~7 (d,2H), 7.66 (d,2H), 8.0 (d,lH), B.22 (s,lH).
Step C: Ethyl (l-methylethyl)carbamate To a solution of ethyl chloroformate (21.7 9, 0.2 mol) in 200 ml ether cooled to 0C was added dropwise 35.7 ml of isopropylamine with stirring and cooling. After complete addition of the amine, the reaction mixture was stirred at room temperature for an additional 0.5 hour. The reaction mixture was filtered, and the ether solution was washed with water, and dried over magnesium sulfate. Evapora-tion of the ether and distillation of the residue in a Kugelrohr apparatus resulted in 22.6 9 of the title compound B.p.: 5~-66C (bath temperature) at 1.5 mm ~ 20 Hg.
:'. ' Step D: Ethyl (chlorosulfenyl)(l-methyl-ethyl)carbamate .
To a solution of ethyl (l-methylethyl)-carbamate (13.1 9, 0.1 mol) in 100 ml methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8.7 3û g, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature . and stirring was continued for additional 1.5 hours.
The mixture was let stand overnight. Methylene ` 35 chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of the pyridine , 2~ fi5 '~ .
hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr 5 apparatus to give 12.5 9 of the title compound Bp:
64-80 (bath temperature) at 1.4 mm Hg.
Step E: 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-tN'-(l-methyl- :.
ethyl)-N'-(ethoxycarbonyl)aminosulfenyl]-2H-benz[g]indazole-2-carboxamide . .
To a solution of the title compound of Step B
(2.0 g, 4.8 mmol) in 50 ml methylene chloride cooled to 0C was added triethylamine (1.0 g, 0.01 mol) and ethyl (chlorosulfenyl)(l-methylethyl)carbamate from Step D (1.4 g, 7.7 mmol). The misture was allowed to warm to room temperature and stirred for one hour.
The crude mixture was purified by silica column chromatography using ether-hexane (1:2) as eluent.
The title compound (2.38 9) was obtained in about 90%
purity (mp: 130-139). Extraction of the product with ether-hexane (2:1) gave 1.8 9 of highly pure ~`
material mp: 139-140C.
lH NMR (CDC13); ô 0.92 (t,3H), 1.26 (d,3H), 1.35 (d,3H), 1.95 (m,lH), 2.7 (m,lH), 2.95 (m,2H), 3.67 (s,3H), 3.8 (m,3H), 4.5 (m,2H), 7.2 (m,3H), 7.45 (d,3H), 7.65 (d,2H).
0 Example 2 ;
3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-~ 14-(trifluoromethYl)PhenYl]-N-(l-methyl-- propo~ylcarbonylsulfenyl)-2H-benzlg]-`; indazole-2-carboxami~e. _ Step A: (l-methylpropoxycarbonyl)sulfenyl chloride .
.
, . . . . . . .
. .
- , ;'. - . ., 21~ 65 Chlorocarbonylsulfenyl chloride (13.1 9, 0.1 mol) was mixed with 2-butanol (6.7 g, 0.09 mol) and 5 warmed to about 35 to 40C for one hour. Distil-lation resulted in the title compound (5.93 g) Bp.
70C/û.8 mm Hg. NMR spectrum was consistent with the structure.
Step B: 3,3a,4,8-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl~-N-(l-methyl-propoxycarbonylsulfenyl)-2H-benz[g]indazole-2-carboxamide.
To a solution of the title compound of Step B
(Example 1) (0.4 9, 0.96 mmol) in 5 ml methylene chloride was added triethylamine (0.12 9~ and cooled to 0C. To this solution was added (l-methylpropoxy-carbonyl)sulfenyl chloride (S'cep A) (0.2 g, 0.0012 - 20 mol). The mixture was stirred at room temperature for one hour. At this stage thin layer `~ chromatography indicated only partial conversion, therefor, addition- al amounts of (l-methylpro-poxycarbonyl)sulfenyl chloride (0.2 9) and 25 triethylamine (0.12 9) was added and the mi~cture was let stand overnight. The reaction mixture was subjected to silica gel column chromatography using ` hexane-ether (7:1) as eluent. The title compound was obtained (0.22 9) in high purity; m.p.: 125-126~C.
30 lH NMR (CDC13): 8 0.9 (m,3H), 1.3 (m,3H), 1.6 (m,2H), 1.9 (m,lH), 2.8 (m,3H), 3.67 (s,3H), 3.8 (d,lH), 4.5 (d,lH), 5.0 (m,lH), 7.05 (m,3H), 7.25 (m,lH), 7.5 (d,2H), 7.57 (d,2H).
! :~
.
, , . . , . ~ . , . . ~ . .
2~C~Q~65 Ex~m~le 3 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4- --5 ' '(trifluoromethyl)phenyl]-N-(dibutylamino-~- sulfe~yl2-2H-benzralindazole-2-carboxamide Step A: N,N'-bis-(dibutylamino)disulfide ~.
To a solution of dibutylamine (52 9, 0.4 mol) in 200 ml hexane cooled to 0C was added sulfur mono-chloride (13.5 g, 0.1 mol) dropwise with stirring over a period of 20 minutes. The reaction mixture was warmed up to ro~m temperature and stirrin~ was continued for 30 minutes. The reaction mixture was filtered and hexane was evaporated to yield 30.1 9 of the title compound.
.
Step B: Dibutylaminosulfenylchloride ~
''~ 20 ' To a solution of N,N'-bis-(dibutylamino)disul-fide (13.2 9, 0.05 mol) in 12 ml carbontetrachloride was added. Sulfuryl chloride (6.75 9, 0.05 mol) was ` added dropwise at ambient temperature. Then heated - 25 to about 60C for 10 minutes, and distilled to give the title compound (7.55 9) as a yellow liquid. Bp:
, 80-87C at 0.6 mm Hg.
... .
~ Step C: 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-'~ 30 (trifluoromethyl)phenyl]-N-(dibutylamino-sulfenyl)-2H-benz[g]indazole-2-carbosamide.
.. .~ .
To a solution of the title compound of ~tep ; B (Example 1) (0.~ 9, 0.96 mmol) in 8 ml methylene chloride cooled to 0C was added triethylamine (0.15 9) and dibutylaminosulfenylchloride (0.2 9).
, '' ' ' - ' .' , . ' . . ~ ~ . ;
~: . , . .: . ~ , , r~
2~!QQ~65 The reaction mixture was warmed to room temperature and stirred for one hour. The mixture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 9) in high purity.
lH NMR (CDC13): ~ 0.7 to 1.7 (m,14H), 1.9 (m,lH), 2.6 to 3.1 (m,7H), 3.67 (s,3H), 3.75 (d,lH), 4.45 (d,lH), 7.1 (m,3H), 7.25 (m,lH), 7.4 (d,2H), 7.6 (d,2H).
Example 4 7-Chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-N--[N'-(methyl)-N'-(hexoxycarbonyl)amino-; sulfenyll-2H-benz~glindazole-2-carbo~amide Step A: ((2-(3-chlorophenyl)ethyl)methanesulfonate To a 0C solution of 30.0 9 of 3-chloro-phenethyl alcohol and 15.3 ml of methane sulfonyl ; chloride in 150 ml of THF was added, dropwise, a solution of 28.0 ml of triethylamine in 50 ml of THF. The reaction was warmed to room temperature, stirred overnight, and then filtered. The filtrate was partitioned between aqueous sodium bicarbonate and ether. The organic extracts were then dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford 45.93 g of a clear, colorless oil. !~
Step B: 3-chlorobenzenebutanoic acid To a mixture of 8.0 9 of 60% sodium hydride in -- 300 ml of ~HF, under N2, was added dropwise a solution of 31.0 ml of diethyl malonate in 50 ml of : . :.
:.
' .: ~ . . : ., - . . , : ~ .. .: . - .
~.^, -ZC~Q~
THF. Upon complete addition of the diethyl malonate, a pale yellow homogenous solution was obtained. To this was added a solution of 45.93 9 of the sulfonate from Step A and the mixture was then heated at reflux overnight. The reaction was then cooled to room temperature, poured into 400 ml of lN HCl, and e~tracted with ether. The ether extracts were dried ~ 10 over magnesium sulfate, filtered and concentrated - under reduced pressure to afford 68.9 g of a yellow oil. The crude oil was dissolved in 400 ml of methanol, 100 ml of H2O and 40 ml of 50% aqueous NaOH. The reaction was stirred overnight and the methanol was then removed at reduced pressure. The crude residue was partitioned between H2O and ether, the aqueous extracts were acidified with concentrated HCl and then extracted several times with ether. The ether e~tracts were dried over magne- sium sulfate, filtered and concentrated to afford 51.7 9 of a yellow oil. The crude residue was dissolved in 200 ml of toluene and heated at reflux for 9 days under N2 to effect decarboxylation. After this time toluene was removed by concentration at reduced 2S pressure to afford 35.72 9 of a yellow oil. lH NMR
- analysis of the crude product was consistent with 3-chlorobenzene- butenoic acid of purity estimated to be 80%. The crude product was used without further purification directly in the next step.
Step C: 6-chloro-3,4-dihydro-1(2H~-naphthalenone A mi~ture of 35.72 of the product from Step and 50 ml of thionyl chloride was heated at reflux 35 for 2 hours and then stirred at room temperature for l `
18 hours. After this time thionyl chloride was ~ . , , :
.
::: , . ~ :: .
2C~ i5 removed at reduced pressure and the product was dissolved in carbon tetrachloride and concentrated at reduced pressure. The residue was dissolved in 150 ml of dichloroethane cooled to 0C and 28 9 of aluminum chloride was added portionwise over about 1 hr in approximately 3 g portions. After stirring for 3 hrs the reaction was poured over a mixture of ice/lN HCl and extracted three times with methylene chloride. The organic extracts were dried sver magnesium sulfate and concentrated to appro~imately 30 9 of a brown oil. Chromatography on silica gel with 10~ ethyl acetate/hexane afforded 17.83 y of 15 6-chloro-3,4-dihydro-1(2H)-naphthalenone as a brown oil. lH NMR was consistent with the structure.
. Step D: 7-chloro-3,3a,4-5-tetrahydro-N-[4-(tri-fluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide ~'. .
~ A mi~ture of 6-chloro-3,4-dihydro-; 1(2H)-naphthalenone (Step C), 2.5 9 of dimethylamine hydrochloride, 1.0 9 of paraformaldehyde, 0.7 ml of 25 concentrated HCl and 15 ml of ethanol was combined ~ i and heated at reflux for 18 hrs. The reaction was then concentrated at re- duced pressure end partitioned between H20 and ether. The aqueous extracts were made baic with lN NaOH and then extracted three times with ether. The ether extracts were dried over magnesium sulfate and concentrated to 4.64 9 of a yellow oil. This compound was dissolved in 25 ml of ethanol and 1.5 ml of hydrazine hydrate was added followed by 5 to 6 drops of 50% sodium hydroxide. The reaction was then heated at reflux, under N2, for 2 to 3 hrs after which time it was cooled and most of the ethanol was removed by . .
- ., . , . . , . . , . ~ : .
2~ 6S
concentration at reduced pressure. The crude residue was partitioned between saturated aqueous sodium bicarbonate and methylene chloride The methylene chloride extracts were dried over mag~esium sulfate and filtered. The methylene chloride extracts were then combined with 3.5 9 of 4-trifluoromethylphenyl isocyanate and stirred under N2 overnight. The reaction was then concentrated and the crude residue triturated with ether to afford 3.35 9 of the title - compound as a white powder, m.p. 196 to 199C.
lH NMR (CDC13) 6 1.9 (m,lH), 2.2 (m,lH), 3.0 (m,2H), - 3.5 (m,2H), 4.43 (m,lH), 7.24 (m,2H), 7.55 (d,2H), 7.67 ~d,2H), 7.92 (d,lH), 8.20 (s,lH).
Step E: 7-chloro-3,3a,4,5-tetrahydro-3a-metho~y-carbonyl-N-[4-(trifluoromethyl)phenyl]-2H-benz[g]indazole-2-carboxamide A solution of 50 ml of THF and 6.7 ml of `. diisopropylamine was cooled under N2 to -78C and then 17.5 ml of 2.5 M n-butyllithium in hexane was added. After 5 min, a solution of 7.8 9 of the title compound of Step D in 15 ml of THF was added dropwise and the dark red solution that formed was stirred at --78C for an additional 15 min. After this time a solution of 4.6 ml of methyl chloroformate in 10 ml of THF was added dropwise and the red color dissipated rapidly. The reaction was warmed to room temperature and after 1 hr quenched with 5~ aqueous sodium bicarbonate. The reaction mi~ture was partitioned between ether and S% aqueous sodium bicarbonate. The ether extracts were dried over magnesium sulfate and concentrated to 14.1 9 of a yellow oily solid. The crude product was triturated ~! , . . .'. . . , :'' ' ' "' ,. . ' ,, ~' ' ' .
' .' ' ' ~
2~ 65 with ether and ~he resulting white precipitate was filtered and dried to afford 5.56 9 of the title compound as a white solid, m.p. 234 to 236C.
1~ NMR(CDC13) ~ 2.1 (m,lH), 2.75 (m,lH~, 2.95 (m,2H), 3.71 (s,3H), 3.75 (d,lH, J-6Hz), 4.59 (d,1H, J-6Hz), 7.25 (m,2H), 7.57 (d,2H), 7.66 (d,2H), 7.94 (d,lH), 8.18 (d,lH).
: 10 ~ Step F: 7-chloro-3,3a,4,5-tetrahydro-3a-metho~y-:~ carbonyl-N-[4-(trifluoromethyl)phPnyl~-N-[N~-(methyl)-N~-(he~oxycarbonyl)amino-sulfenyl]-2H-benz[g]indazole-2-carboxamide To a suspension of the title compound of Step E above (2.2 g, 0.005 mol) in 25 ml methylene chloride cooled to 0C was added triethylamine (1.0 g) and hexyl (chlorosulfenyl)(methyl)carbamate, (prepared in a manner similar to ~ample 1, Step D), ~ (2.5 g 75% pure) dropwise at 0C. The mi~ture was ; stirred at room temperature for additional one hour. -The reaction mixture was concentrated under high vacuum and subjected to silica gel column chromatography using hexane-ether (1:1) as an eluent. The title compound (2.5 9) was obtained, melting point 12B-129C in high purity.
H NMR (CDC13) ~ 0.87 (t,3H), l.lB (m,8H), 1.9(m,1H), 2.8 (m,3H), 3.5 (s,3H), 3.66 (s,3H), 3.7 (m,3H), 4.5 (d,lH), 7.05 sm~3H)~ 7.35 (d,2H), 7.6 (d,2H).
Vsing the procedures described in Examples 1 to 4 with obvious modifications, the compounds e~emplified in E~amples S to 28 were prepared.
- j : :
:: ., .
..
. ~ .
2C~Q~65 T~ble A
R
~ O~CH9 N -N
CF3 ~N- S- Z
., . ~
Ex~mple R2 Z m.p. C lH NMR (~ iD ppm) , i~ CDC13 :?
~ S H N(CH3)C(O)OCgH9 134 1.0(t,3H), 1.2(m,4H?, 'r I.9(m,lH), 2.6-3(m,3H), 3.5(s,3H), 3.66(s,3H), '~ 25 3.7(m,2H), 3.7S(d,lH), ~, 4.45(d,1H),7.1(m,3H), 7.25(m,lH), 7.35(d,2H), 7.6(d,2H). ~;
WO 88/OS046. .
. .
;,'.
, , , , ~, . , , " ., .. - . , , . . , . - . . . ~ .
2(~ 65 ~, ~..
Sulfenyl halides of the type XSY (Formula IV) wherein X and Y are as specified in this disclosure are known in the literature. A review article by Kule in Synthesis, 561, ~1970) describes the chemistry and preparation of the majority of sulfenyl halides utilized in this invention. The synthesis of N-chlorosulfenylcarbamates was described in U.S.
3,843,689. Other sulfenyl halides can be prepared by the general procedures described in these literature e~amples or obvious modifications thereof.
Compounds of Formula I (Q is other than SX) are synthesized from compounds of Formula VI.
15 Reaction of compounds of Formula VI in the presence :
of an acid acceptor with electrophilic - carbonyl-containing reagents results in substitution on nitrogen. Strong bases known to deprotonate ureas such as potassium t-butoxide, potassium hydride and sodium hydride are the preferred acid acceptors in the process. Suitable electrophiles include, but are ; not restricted to , acyl halides, acid anhydrides, carbonates, and chloroformates. The reaction sequence is normally run in the temperature range of -10 to 25C, but can be run at temperatures as high ` as 110C or as low as -50C in certain cases.
Solvents which are not deprotonated under the conditions of the reaction such as tetrahydrofuran, dimethylformamide, dimethoxyethane, and diethyl ether -~
-': ,; -, .
, . ' . ~ ! , . . . .
X~QC~65 are preferred. The electrophiles used in this process are well known to those skilled in the art and are generally commercially available.
Acïd Acceptor VI ~ QX
.. 10 wherein: ;
; QX is selected from acyl halides, chloroformates a~d acid anhydrides.
The following Examples illustrate the invention.
;~ . , ' Example_1 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)pheny]-N-[N'-(l-methyl-ethyl)-N'-(etho~ycarbonyl)aminosulfenyl]-2H-benz~alindazole-2-carbo~amide :
Step A: 3,3a,4,5-Tetrahydro-N-[4-~trifluoromethyl)-phenyl]-2H-benz[g]indazole-2-carboxamide A mixture of 10.0 9 of -tetralone, 2.0 9 of paraformaldehyde, 6.5 9 of dimethylamine hydrochloride and 1.75 ml of conc. HCl in 20 ml of ethanol was heated at reflux for 24 h, cooled to room temperature and then partitioned between ether and . water. The aqueous extracts-were made basic with lN
aqueous NaOH and e~tracted with ether. The ether extracts were dried over magnesium sulfate and ~-concentrated to 12.3 g of a yellow oil. The residual oil was dissolved in 40 ml of n-propyl alcohol, combined with 6.7 ml of hydrazine hydra~e and heated .' ~,: ..
- v . .
" . :~ . . . : : : ~ : . . :: ~ : :
Z(?Q~65 at reflu~ for 1 h. The reaction mixture was then concentrated under vacuum, partitioned between 5%
aqueous NaHCO3 and methylene chloride and dried over magnesium sulfate. To the methylene chloride :
extracts were added 12.5 9 of 4-trifluoro-methylphenyl isocyanate and the mixture was then re-fluxed o~e hour, cooled to room temperature and con-centrated to 26.1 9 of a brown oil. Chromatography on silica gel followed by trituration with ether afforded 11.78 g of the title compound as a tan powder, m.p. 149-151C.
lH NMR (CDC13), ~ 1.9 (m,lH), 2.4 (m,lH), 3.0 (m, - 15 2H), 3.5 (m,2H), 4.4 (m,lH), 7.3 (m,3H), 7.58 (d,2H), 7.65 (d,2H), 8.0 (d,2H), 8.3 (bs,lH).
;.' Step B: 3,3a,4,5-tetrahydro-3a-metho~ycarbonyl-N-[4'-(trifluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide ,, :
; To a solution of 0.9 ml of diisopropylamine in 10 ml of THF, at -78C, was added 2.3 ml of 2.5 M
n-butyl lithium in hexane and the mi~ture was stirred -25 for 5 mins. To this solution was added a solution of 1.0 9 of the title compound of Step A in 5 ml of THF. The reaction was warmed to 0C, recooled to -78C and then 0.75 ml of methyl chloroformate was added. The reaction mixture was then stirred for 24 ; 30 h, with gradual warming to room temperature, quenched with 0.5 ml of glacial acetic acid, and poured into a 5% solution of aqueous NaHCO3. The mi~ture was ; extracted with chloroform, dried over magnesium sulfate and concentrated. Chromatography on silica 35 gel with 30% ethyl acetate he~ane afforded 0.25 9 of the title compound, m.p. 177 to 180C.
. . .
"' :- ' ' ' ' , ' . ' ,~
:
2~ 65 :
lH NMR (CDC13), 6 2.1 (m,lH), 2.7 (m,lH), 3.0 (m,2H), 3.71 (s,3H), 3.76 (d,lH), 4.5~ (d,lH), 7.3 (m,3H), 7.~7 (d,2H), 7.66 (d,2H), 8.0 (d,lH), B.22 (s,lH).
Step C: Ethyl (l-methylethyl)carbamate To a solution of ethyl chloroformate (21.7 9, 0.2 mol) in 200 ml ether cooled to 0C was added dropwise 35.7 ml of isopropylamine with stirring and cooling. After complete addition of the amine, the reaction mixture was stirred at room temperature for an additional 0.5 hour. The reaction mixture was filtered, and the ether solution was washed with water, and dried over magnesium sulfate. Evapora-tion of the ether and distillation of the residue in a Kugelrohr apparatus resulted in 22.6 9 of the title compound B.p.: 5~-66C (bath temperature) at 1.5 mm ~ 20 Hg.
:'. ' Step D: Ethyl (chlorosulfenyl)(l-methyl-ethyl)carbamate .
To a solution of ethyl (l-methylethyl)-carbamate (13.1 9, 0.1 mol) in 100 ml methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8.7 3û g, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature . and stirring was continued for additional 1.5 hours.
The mixture was let stand overnight. Methylene ` 35 chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of the pyridine , 2~ fi5 '~ .
hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr 5 apparatus to give 12.5 9 of the title compound Bp:
64-80 (bath temperature) at 1.4 mm Hg.
Step E: 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl]-N-tN'-(l-methyl- :.
ethyl)-N'-(ethoxycarbonyl)aminosulfenyl]-2H-benz[g]indazole-2-carboxamide . .
To a solution of the title compound of Step B
(2.0 g, 4.8 mmol) in 50 ml methylene chloride cooled to 0C was added triethylamine (1.0 g, 0.01 mol) and ethyl (chlorosulfenyl)(l-methylethyl)carbamate from Step D (1.4 g, 7.7 mmol). The misture was allowed to warm to room temperature and stirred for one hour.
The crude mixture was purified by silica column chromatography using ether-hexane (1:2) as eluent.
The title compound (2.38 9) was obtained in about 90%
purity (mp: 130-139). Extraction of the product with ether-hexane (2:1) gave 1.8 9 of highly pure ~`
material mp: 139-140C.
lH NMR (CDC13); ô 0.92 (t,3H), 1.26 (d,3H), 1.35 (d,3H), 1.95 (m,lH), 2.7 (m,lH), 2.95 (m,2H), 3.67 (s,3H), 3.8 (m,3H), 4.5 (m,2H), 7.2 (m,3H), 7.45 (d,3H), 7.65 (d,2H).
0 Example 2 ;
3,3a,4,5-Tetrahydro-3a-metho~ycarbonyl-N-~ 14-(trifluoromethYl)PhenYl]-N-(l-methyl-- propo~ylcarbonylsulfenyl)-2H-benzlg]-`; indazole-2-carboxami~e. _ Step A: (l-methylpropoxycarbonyl)sulfenyl chloride .
.
, . . . . . . .
. .
- , ;'. - . ., 21~ 65 Chlorocarbonylsulfenyl chloride (13.1 9, 0.1 mol) was mixed with 2-butanol (6.7 g, 0.09 mol) and 5 warmed to about 35 to 40C for one hour. Distil-lation resulted in the title compound (5.93 g) Bp.
70C/û.8 mm Hg. NMR spectrum was consistent with the structure.
Step B: 3,3a,4,8-Tetrahydro-3a-methoxycarbonyl-N-[4-(trifluoromethyl)phenyl~-N-(l-methyl-propoxycarbonylsulfenyl)-2H-benz[g]indazole-2-carboxamide.
To a solution of the title compound of Step B
(Example 1) (0.4 9, 0.96 mmol) in 5 ml methylene chloride was added triethylamine (0.12 9~ and cooled to 0C. To this solution was added (l-methylpropoxy-carbonyl)sulfenyl chloride (S'cep A) (0.2 g, 0.0012 - 20 mol). The mixture was stirred at room temperature for one hour. At this stage thin layer `~ chromatography indicated only partial conversion, therefor, addition- al amounts of (l-methylpro-poxycarbonyl)sulfenyl chloride (0.2 9) and 25 triethylamine (0.12 9) was added and the mi~cture was let stand overnight. The reaction mixture was subjected to silica gel column chromatography using ` hexane-ether (7:1) as eluent. The title compound was obtained (0.22 9) in high purity; m.p.: 125-126~C.
30 lH NMR (CDC13): 8 0.9 (m,3H), 1.3 (m,3H), 1.6 (m,2H), 1.9 (m,lH), 2.8 (m,3H), 3.67 (s,3H), 3.8 (d,lH), 4.5 (d,lH), 5.0 (m,lH), 7.05 (m,3H), 7.25 (m,lH), 7.5 (d,2H), 7.57 (d,2H).
! :~
.
, , . . , . ~ . , . . ~ . .
2~C~Q~65 Ex~m~le 3 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4- --5 ' '(trifluoromethyl)phenyl]-N-(dibutylamino-~- sulfe~yl2-2H-benzralindazole-2-carboxamide Step A: N,N'-bis-(dibutylamino)disulfide ~.
To a solution of dibutylamine (52 9, 0.4 mol) in 200 ml hexane cooled to 0C was added sulfur mono-chloride (13.5 g, 0.1 mol) dropwise with stirring over a period of 20 minutes. The reaction mixture was warmed up to ro~m temperature and stirrin~ was continued for 30 minutes. The reaction mixture was filtered and hexane was evaporated to yield 30.1 9 of the title compound.
.
Step B: Dibutylaminosulfenylchloride ~
''~ 20 ' To a solution of N,N'-bis-(dibutylamino)disul-fide (13.2 9, 0.05 mol) in 12 ml carbontetrachloride was added. Sulfuryl chloride (6.75 9, 0.05 mol) was ` added dropwise at ambient temperature. Then heated - 25 to about 60C for 10 minutes, and distilled to give the title compound (7.55 9) as a yellow liquid. Bp:
, 80-87C at 0.6 mm Hg.
... .
~ Step C: 3,3a,4,5-Tetrahydro-3a-methoxycarbonyl-N-[4-'~ 30 (trifluoromethyl)phenyl]-N-(dibutylamino-sulfenyl)-2H-benz[g]indazole-2-carbosamide.
.. .~ .
To a solution of the title compound of ~tep ; B (Example 1) (0.~ 9, 0.96 mmol) in 8 ml methylene chloride cooled to 0C was added triethylamine (0.15 9) and dibutylaminosulfenylchloride (0.2 9).
, '' ' ' - ' .' , . ' . . ~ ~ . ;
~: . , . .: . ~ , , r~
2~!QQ~65 The reaction mixture was warmed to room temperature and stirred for one hour. The mixture was subjected to silica gel column chromatography using hexane-ether (6:1) as the eluent. The title compound was obtained (0.24 9) in high purity.
lH NMR (CDC13): ~ 0.7 to 1.7 (m,14H), 1.9 (m,lH), 2.6 to 3.1 (m,7H), 3.67 (s,3H), 3.75 (d,lH), 4.45 (d,lH), 7.1 (m,3H), 7.25 (m,lH), 7.4 (d,2H), 7.6 (d,2H).
Example 4 7-Chloro-3,3a,4,5-tetrahydro-3a-methoxy-carbonyl-N-[4-(trifluoromethyl)phenyl]-N--[N'-(methyl)-N'-(hexoxycarbonyl)amino-; sulfenyll-2H-benz~glindazole-2-carbo~amide Step A: ((2-(3-chlorophenyl)ethyl)methanesulfonate To a 0C solution of 30.0 9 of 3-chloro-phenethyl alcohol and 15.3 ml of methane sulfonyl ; chloride in 150 ml of THF was added, dropwise, a solution of 28.0 ml of triethylamine in 50 ml of THF. The reaction was warmed to room temperature, stirred overnight, and then filtered. The filtrate was partitioned between aqueous sodium bicarbonate and ether. The organic extracts were then dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford 45.93 g of a clear, colorless oil. !~
Step B: 3-chlorobenzenebutanoic acid To a mixture of 8.0 9 of 60% sodium hydride in -- 300 ml of ~HF, under N2, was added dropwise a solution of 31.0 ml of diethyl malonate in 50 ml of : . :.
:.
' .: ~ . . : ., - . . , : ~ .. .: . - .
~.^, -ZC~Q~
THF. Upon complete addition of the diethyl malonate, a pale yellow homogenous solution was obtained. To this was added a solution of 45.93 9 of the sulfonate from Step A and the mixture was then heated at reflux overnight. The reaction was then cooled to room temperature, poured into 400 ml of lN HCl, and e~tracted with ether. The ether extracts were dried ~ 10 over magnesium sulfate, filtered and concentrated - under reduced pressure to afford 68.9 g of a yellow oil. The crude oil was dissolved in 400 ml of methanol, 100 ml of H2O and 40 ml of 50% aqueous NaOH. The reaction was stirred overnight and the methanol was then removed at reduced pressure. The crude residue was partitioned between H2O and ether, the aqueous extracts were acidified with concentrated HCl and then extracted several times with ether. The ether e~tracts were dried over magne- sium sulfate, filtered and concentrated to afford 51.7 9 of a yellow oil. The crude residue was dissolved in 200 ml of toluene and heated at reflux for 9 days under N2 to effect decarboxylation. After this time toluene was removed by concentration at reduced 2S pressure to afford 35.72 9 of a yellow oil. lH NMR
- analysis of the crude product was consistent with 3-chlorobenzene- butenoic acid of purity estimated to be 80%. The crude product was used without further purification directly in the next step.
Step C: 6-chloro-3,4-dihydro-1(2H~-naphthalenone A mi~ture of 35.72 of the product from Step and 50 ml of thionyl chloride was heated at reflux 35 for 2 hours and then stirred at room temperature for l `
18 hours. After this time thionyl chloride was ~ . , , :
.
::: , . ~ :: .
2C~ i5 removed at reduced pressure and the product was dissolved in carbon tetrachloride and concentrated at reduced pressure. The residue was dissolved in 150 ml of dichloroethane cooled to 0C and 28 9 of aluminum chloride was added portionwise over about 1 hr in approximately 3 g portions. After stirring for 3 hrs the reaction was poured over a mixture of ice/lN HCl and extracted three times with methylene chloride. The organic extracts were dried sver magnesium sulfate and concentrated to appro~imately 30 9 of a brown oil. Chromatography on silica gel with 10~ ethyl acetate/hexane afforded 17.83 y of 15 6-chloro-3,4-dihydro-1(2H)-naphthalenone as a brown oil. lH NMR was consistent with the structure.
. Step D: 7-chloro-3,3a,4-5-tetrahydro-N-[4-(tri-fluoromethyl)phenyl]-2H-benz[g]-indazole-2-carboxamide ~'. .
~ A mi~ture of 6-chloro-3,4-dihydro-; 1(2H)-naphthalenone (Step C), 2.5 9 of dimethylamine hydrochloride, 1.0 9 of paraformaldehyde, 0.7 ml of 25 concentrated HCl and 15 ml of ethanol was combined ~ i and heated at reflux for 18 hrs. The reaction was then concentrated at re- duced pressure end partitioned between H20 and ether. The aqueous extracts were made baic with lN NaOH and then extracted three times with ether. The ether extracts were dried over magnesium sulfate and concentrated to 4.64 9 of a yellow oil. This compound was dissolved in 25 ml of ethanol and 1.5 ml of hydrazine hydrate was added followed by 5 to 6 drops of 50% sodium hydroxide. The reaction was then heated at reflux, under N2, for 2 to 3 hrs after which time it was cooled and most of the ethanol was removed by . .
- ., . , . . , . . , . ~ : .
2~ 6S
concentration at reduced pressure. The crude residue was partitioned between saturated aqueous sodium bicarbonate and methylene chloride The methylene chloride extracts were dried over mag~esium sulfate and filtered. The methylene chloride extracts were then combined with 3.5 9 of 4-trifluoromethylphenyl isocyanate and stirred under N2 overnight. The reaction was then concentrated and the crude residue triturated with ether to afford 3.35 9 of the title - compound as a white powder, m.p. 196 to 199C.
lH NMR (CDC13) 6 1.9 (m,lH), 2.2 (m,lH), 3.0 (m,2H), - 3.5 (m,2H), 4.43 (m,lH), 7.24 (m,2H), 7.55 (d,2H), 7.67 ~d,2H), 7.92 (d,lH), 8.20 (s,lH).
Step E: 7-chloro-3,3a,4,5-tetrahydro-3a-metho~y-carbonyl-N-[4-(trifluoromethyl)phenyl]-2H-benz[g]indazole-2-carboxamide A solution of 50 ml of THF and 6.7 ml of `. diisopropylamine was cooled under N2 to -78C and then 17.5 ml of 2.5 M n-butyllithium in hexane was added. After 5 min, a solution of 7.8 9 of the title compound of Step D in 15 ml of THF was added dropwise and the dark red solution that formed was stirred at --78C for an additional 15 min. After this time a solution of 4.6 ml of methyl chloroformate in 10 ml of THF was added dropwise and the red color dissipated rapidly. The reaction was warmed to room temperature and after 1 hr quenched with 5~ aqueous sodium bicarbonate. The reaction mi~ture was partitioned between ether and S% aqueous sodium bicarbonate. The ether extracts were dried over magnesium sulfate and concentrated to 14.1 9 of a yellow oily solid. The crude product was triturated ~! , . . .'. . . , :'' ' ' "' ,. . ' ,, ~' ' ' .
' .' ' ' ~
2~ 65 with ether and ~he resulting white precipitate was filtered and dried to afford 5.56 9 of the title compound as a white solid, m.p. 234 to 236C.
1~ NMR(CDC13) ~ 2.1 (m,lH), 2.75 (m,lH~, 2.95 (m,2H), 3.71 (s,3H), 3.75 (d,lH, J-6Hz), 4.59 (d,1H, J-6Hz), 7.25 (m,2H), 7.57 (d,2H), 7.66 (d,2H), 7.94 (d,lH), 8.18 (d,lH).
: 10 ~ Step F: 7-chloro-3,3a,4,5-tetrahydro-3a-metho~y-:~ carbonyl-N-[4-(trifluoromethyl)phPnyl~-N-[N~-(methyl)-N~-(he~oxycarbonyl)amino-sulfenyl]-2H-benz[g]indazole-2-carboxamide To a suspension of the title compound of Step E above (2.2 g, 0.005 mol) in 25 ml methylene chloride cooled to 0C was added triethylamine (1.0 g) and hexyl (chlorosulfenyl)(methyl)carbamate, (prepared in a manner similar to ~ample 1, Step D), ~ (2.5 g 75% pure) dropwise at 0C. The mi~ture was ; stirred at room temperature for additional one hour. -The reaction mixture was concentrated under high vacuum and subjected to silica gel column chromatography using hexane-ether (1:1) as an eluent. The title compound (2.5 9) was obtained, melting point 12B-129C in high purity.
H NMR (CDC13) ~ 0.87 (t,3H), l.lB (m,8H), 1.9(m,1H), 2.8 (m,3H), 3.5 (s,3H), 3.66 (s,3H), 3.7 (m,3H), 4.5 (d,lH), 7.05 sm~3H)~ 7.35 (d,2H), 7.6 (d,2H).
Vsing the procedures described in Examples 1 to 4 with obvious modifications, the compounds e~emplified in E~amples S to 28 were prepared.
- j : :
:: ., .
..
. ~ .
2C~Q~65 T~ble A
R
~ O~CH9 N -N
CF3 ~N- S- Z
., . ~
Ex~mple R2 Z m.p. C lH NMR (~ iD ppm) , i~ CDC13 :?
~ S H N(CH3)C(O)OCgH9 134 1.0(t,3H), 1.2(m,4H?, 'r I.9(m,lH), 2.6-3(m,3H), 3.5(s,3H), 3.66(s,3H), '~ 25 3.7(m,2H), 3.7S(d,lH), ~, 4.45(d,1H),7.1(m,3H), 7.25(m,lH), 7.35(d,2H), 7.6(d,2H). ~;
6 B N(CH3)C(O)OC2Hs 121-123 0.88(t,3N), l.9(m,1H), -~ 30 2.6-3(m,3H), 3.5(s,3H), 3.66 (s,3H), 3.8~m,3H), 4.47~d,1H), 7.11(m,3H), 7.25 (m,lH), 7,35(d,2H), , 7.6(d,2H).
.
Q~L6S
Example R2 Z m.p. C lH NMR l~ in ppm) ~n C~C13 .
7 6-F N(CH3)C(O)OC4H9 120 0.83(t,3H), 1.2(m,4H), 1.85(m,1H), 2.7(m,2H), 3.0(m,1H), 3.5(~,3H), 3.66(6,3H), 3.75(m,3H).
4.5(d,1H), 7.0~m,3H), 7.35 ( d ,2H ) , 7.6 ( d ,3H ) .
.
Q~L6S
Example R2 Z m.p. C lH NMR l~ in ppm) ~n C~C13 .
7 6-F N(CH3)C(O)OC4H9 120 0.83(t,3H), 1.2(m,4H), 1.85(m,1H), 2.7(m,2H), 3.0(m,1H), 3.5(~,3H), 3.66(6,3H), 3.75(m,3H).
4.5(d,1H), 7.0~m,3H), 7.35 ( d ,2H ) , 7.6 ( d ,3H ) .
8 N N~CH3~C~O)OcycloC6H11 175-176 0.6-1.7(m,10H), l.9(m,1H), 2.6-3.0(m,3H), 3.51(s,3H), 3.65(6,3B), 3.75(d,1H), 4.35(m,1H), 4.45 (d,lH), ' 7,1(m,3H), 7.25(m,1H), 7.35(d,2H), 7.6(d,2H).
- g H N(cH3)c(o)oc8Hl7 144-145 0.88(t,3H), 1.21(m,12H), l.9(m,1H), 2.7(m,1H), `~ 2.9(m,2H), 3.5(m,3H), ,. 3.65(m,3H), 3.75(m,3H), 4.5(d, lH), 7.1(m,3H), :...
7.25(m,1H), 7.35(d,2H), . 25 7.6 ( d ,2H ) .
H N(CH3)c(O)ocloH2l 76-78 0.88(t,3H), 1.25(m,16H), l.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.5~s,3H), "7 3.66(~,3H), 3.75(m,3H), ' 30 4.5(d,lH), 7.15(m,3H), ~ .
.. . . .
7.25(m, lH), ? .35(d,2H), `
7.6 (d,2H).
.i~ .
, . . .
~ 35 .
.', ~' ' ~', ' ',: ' .
2~()Qt~iS
Example R2 Z m.p.C lH NMR (~ in ppm) _ _ _ 1D CDC13 . .
11 6-F N-[CH(CH3)2]C(O)OC2Hs 143-5 O.91(t,3H), 1.27td,3H), 1.35~d,3H), 1.3tm,lH), 2.75(m,2H), 3.05(m,lN), 3.67(s,3H), 3.75(m,3H), 4.5(m,2H), 7.25(m,3H), 7.45(d,2H), 7.6(d,2H).
12 H N(CH3)c(O)ocl2H25 0.88(t,3H), 1.26(m,20H), l.9(m,1H), 2.7(m,1H), 2.9¦m,2H), 3.5(~,3N), 3.66(s,3H), 3.75(m,3H), .S(d,lH), 7.1(m,3H), 7.25(m,1H), 7.35(d,2H), 7.6(d,2H).
13 H N(CH3)c(O)oc6Hl3 0.88(t,3H), 1.26(m,8H), l.9(m,1H), 2.7(m,1N), - 2.9(m,2H), 3.51(s,3H), 3.66(s,3H), 3.75(m,3H), 4.5(d,2H), 7.1(m,3H), :~ 25 7.25(m,1H), 7.35(d,2H), 7.6(d,2H).
. 14 7-Cl C(O)O-sec-C4H9 132 0088(t,3H), 1.3(m,3H), 1.6(m,2H), l.9(m,1H), ` 2.6-3.0(m,3H), 3.88(~,3H), 3.8(d,1H), 4.5(d,1H), 5.0(m,1H), 7.0(m,3H), 7.35(d,2N), 7.6(d,2H).
7-Cl N-tcH(cH3)2lc(o)oc2H5 152 O.9(t,3H), 1.26(d,3H), 1.35(d,3H), l.9tm,1H), ;` 35 2.7(m,1H), 2.9(m,2H), 3.67(s,3H), 3.8(m,3H), 4.5(m,2H), 7.14(m,2H), - 7.4(m,3H), 7.6(d,2H).
.. ..
2~0Q~65 ! -` 31 . .
E~ample R2 Z m.p. C lH NMR (6 i~ ppm) ~n CDC13 _ --16 7-Cl N(CH3)C(O)OC2H5 0.88(t,3H), l.9(m~1HJ, 2.65(m,1H), 2.9(m,2H), 3.49(6,3H), 3.66(~,3H), 3.8(m,3H), 4.5(d,lH), 7.07(m, 3H), 7.35(d,2H), 7.6(d,2H).
17 7-Cl N(CH3)c(O)oc8~l7 103-106 0.88(t,3H~, 1.23(m,12H), , l.9(m,1H), 2.65(m,1H), , 15 2.85(m,2H), 3.5(6,3H), 3.66(6,3H), 3.75(m,3H), :
4.45(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(~,2H).
18 6-F C(O)O-sec-C4H9 125-126 0.9(m,3H), 1.3(m,5H), ~
l.9(m,1H), 2.75(m,2H), ~;
3.0(m,1H), 3.7(6,3H), 3.8(d,lH), 4.5(d,lH), '~ 5.0(m,1H), 6.8(m,1H), ,.~ .~.
7.05(m,2H), 7.45(d,2H) .c 25 7.6(d,2H).
. ~ .
~0 19 7-Cl N(CH3)C(O)OC4Hg 125-127 0.82(m,3H), 1.2(m,4H), .5 1 . 9(m,lH), 2.65(m,lH), 2.85(m,2H), 3.5(6,3H), ~; .
` 3.66~s,3H), 3.7S(m,3H), â~ 4.45(d,1H), 7.05(m,3H), ~ 7.35(d,2H), 7.6(d,2H).
;~ 20 7-Cl N[cH(cH3)2]c(o)oc4H9 - 0.84(t,3H), 1.25(m,10H), ~-~ 1.9(m,1H), 2.65(m,1H), i 3.66(E,3H~, 3.7(m,3H), 4.45(m,2H), 7.15(m,2H), 7.4(m,3N), 7.6(d,2H).
J
. . :.
'~
., ~ .
~QQ~65 Example R2 Z m.p. C lH NMR (~ in ppm) S ~ - in CDC~3 21 7-Cl N(CH3)C(O)ocl2H25 0.88(t,3H), 1.2(m,20H), l.9(m,lH), 2.65(m,lH), 2.9(m,2H), 3.5(6,3H), 3.67(s,3H), 3.75(m,3H), 4.5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
22 7-Cl N(CH3)C(O)O-cycloC6H11 87-91 0.8-1.7(BroDd m,lOH), 2.65(m,1H), 2.9(m,2H), 3.51(s,3H), 3.66(~,3H), 3.75(d,1H), 4.35(m,1H), 4.45(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
23 7-Cl N(CH3)C(O)O(CH2)20C4Hg - 0.9 ~t,3H3, 1.4 (m,4H) 1.9 (m,lH), 2.7 (m,lH?
2.9 (m,2H), 3.3 (m,4H) 3.5 (b,3H), 3.67 (s,3H), ` 3.9 (m,3H), 4.5 (d,lH), 7.1 (m,3H), 7.4 (d,2H), 7.6 ~d,2H).
24 7-Cl N(CH3)C(O)Ocl4H29 0.87 (t,3H), 1.26 (m,24H), 1.9 (m,lH), 2.65 (m,lH), ' 2.9 ~m,2H), 3.5 (s,3H), r. 3.68 (s,3H), 3.75 (m,3H), ' 30 4.47 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.57 (d,2H).
7-Cl N~CH3)C(O)OC16H33 ~ 0.87 (t,3H), 1.26 (m,28H), 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 (s,3H), 3.75 (m,3H), 4.47 (d,lH), 7.C5 (m,3H), 7.35 ~d,2H), 7.6 (d,2H).
.
~` :
.
Example R2 Z m.p. C lH NMR (~ in ppm) ~ CD~13 26 7-Cl N(cH3)c(o)ocl8H37 ~ 0.9 (t,3H), 1.26 (m,32H), - 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 (m,3H), 3.75 (m,3H), ,~ 4.5 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.6 (d,2Ht.
27 7-Cl N(cH3)c(o)oc22H45 0.8B ~t,3H), 1.26 (m,407a), -1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.65 (m,3H), 3.75 (m,3H), 4.4B (d,lH), 7.06 (m,3H), 7.35 (d,2H), 7.6 (d,2H).
28 7-Cl N(CH3)c(O)O(cH2)20(cH2)2oc4H9 0.91 (t,3H), 1.4 (m,4H), - 20 1.9 (m,lH), 2.7 (m,lH), 2.9 (m,2B), 3.5 (s,3H), 3.67 (s,3H), 3.7 tm~9H)~ -4.0 (m,lH), 4.2 (m,lH), , 4.5 (d,lH), 7.6 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
... . .
,~ , .
.~ " .
',7 ':
~), '.
., '.''~.
... . : .
', , 2(~Q~65 E~ample 29 1-(4-chlorophenyl~-5-(4-fluorophenyl~-4,5-dihydro-N- ;
'[4-(trifluoromethyl)phenyl]-N-lN'-(l-methylethyl)-N'-(ethoxycarbonyl)aminothiol]-lH-pyrazole-3-_carboxamide Step A: Ethyl (chlorosulfenyl)(l-methylethyl)-carbamate To a solution of ethyl (l-methylethyl)carbamate (13.1 9, 0.1 mol) in 100 ml of methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8.7 g, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature and stirring was continued for additional 1.5 hours.
The mixture was let stand overnight. Methylene chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of pyridine hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr apparatus to give 12.5 9 of the title Compound B.P.:
64-80 (bath temp.) ~.
Step B: 1-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyl]-N-lN'-(l-methylethyl)-N'-(ethoxycarbonyl)-aminothiol]-lH-pyrazole-3-carbo~amide To a solution of 1-(4-chlorophenyl)-5-(~-fluoro-phenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyll-lH-pyrazole-3-carboxamide (0.95 9, 0.002 mol) in 10 ml :
.. : .. . . . .
2C~QQ~65 . .
of methylene chloride cooled to QC was added triethylamine (0.25 9) followed by the title compound of Step A (0.5 9, 0.0025 mol). The reaction mi~ture was allowed to warm to room temperature with stirring for one hour. Methylenç chloride (50 ml) was added and the mi~ture was washed with water, dried over magnesium sulfate and filtered. The solvent was evaporated and the residue was purified by silica gel column chromatograph using hexane:ether (2:1~ as the eluent. Obtained 1.0 g of the title compound, m.p.: 136-137C, 'H-NMR (CDC13); ~ 7.7 (d,ZH), 7.4 (~, 2H), 7.0 (m, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 15 4.5 (m, lH), 3.75 (m, 3H), 3.05 td of d, lH) 1.3 (d of d, 6H), 0.87 (t, 3H).
.
Example 30 3,9-bis-(4-chlorophenyl)-N-[4-(trifluoromethyl)-20 phenyl]-N-[N'-(l-methylethyl)-N'-(etho~ycarbonyl)-aminothioll-4.5-dihydro-lH-pyraz~lç-l-car~Qxamide ,: i . : .
To a solution of 3,4-bis-(4-chlorophenyl)-N-[4-(trifluoromethyl)phenyl)~-4,5-dihydro-lH-pyrazole-25 l-carboxamide (0.466 9, 0.001 mol) in 5 ml of - methylene chloride cooled to 0C was added 0.3 9 of triethylamine and ethyl (chlorosulfenyl)(l-methyl-: ethyl)carbamate (0.5 9). The mi~ture was allowed to warm to room temperature and let stand overnight. 20 - 30 ml CH2C12 was added and the mi~ture was washed with water and dried over MgSO4 and filtered. The solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using - CH2C12:Butylchloride mi~ture (1:1) as a primary eluent followed by ether. The title compound was obtained in high purity (0.28 9), m.p.: 65-68C.
:
: , ' .: : .
,: , . . .
.
.. ... . ..
~?a!Q~.65 lH-NMR (CDC13), ~ 7.65 ~d, 2H), 7.5 (d, 2H), 7-27 (d, 2H), 7.17 (S, 4H), 7.0 (d, 2H), 4.6-4.3 (m, 3H), 3.95 (d of d, lH), 3.8 (q, 2H), 1.3 (m, 6H), 0.95 (t, 3H).
The following additional Examples (Tables B
and C) employed procedures similar to those described in the previous E~amples 29 and 30 or in the disclosed literature.
.
~ 15 . ' ~ .
. .
:.
:. ~O
.
35 ~
. .
., .
, ,. , .- :: . - -2(~Q(:~6S
~able B
Cl ~ N S
~ ~ C~3 Example X m.p.C 'H-NMR (6 in ppm) in CDC13 ,~ . .
N[cH(cH3)2]c(o)oc4H9 165-170 7.23 (d, 2H), ?.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), 5.2 (d of a, lH), 4.5 (M, lH), 3.75 (M, 3H), 3.1 (a of d, lH), 1.4-1.1 (M, lOH), .85 (t, 3H) 32 N[CH(CH3)(c2Hs)]c(O)oc2H5 ~ 7.23 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 4.5 (N, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.8-1.1 ;-(M, 5H), 0.9 (M, 6H).
.
2~Q~6ti Example X m.p.C 'H-NMR ~ ~n ppm) ~n CDC13 .
:
,. .
33 C(O)OCH(CH3)(C2H5) 159-161 7.25 (d, 2H), 7.55 (d, 2H), 7.0 (M, 6H), 6.25 (d, 2H), 0 5.2 (d of d, lH), 5.0 ~M, lH), 3.75 (d of d, lH3, 3.1 (d of d, lH), 1.65 (M, 2H), 1.28 (d, 3H), 0.9 (t, 3H).
34 N(CH3)C(O)O(cyclo C6Hll) 147-150 7.2 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), -5.2 (d of d, lH), 4.3 (M, lH), 3.7 (d of d, lH), 3.5 (5, 3H), 3.2 (d of d, lH), l.B-0.9 (M, lOH).
':
. ".
. :
~"' ' ' :'.` ..
.. . .
... :
.. . .
-:.
~`', , ' -' .
, . . .
,. . . .
;~ . :
~,: - ,. , -: . : : . - - . .: . . : : . .
::: . - : . , . . ,: . - . . . . .
2~ S
~ 39 .
Table C
.
. 5 :
, .
10 C~ ~R3 : N ~
O=Cj . :~, ~ ~Q
R1 :'-''`.` "' ~i 20 .. ~ .
,j. :
- EX- Q R3 Rl m.p.C 'H-NMR (~ in ppm) ~` ~_ , ,, ~ 35 S-N(CH3)CIO)O-ce~-C4H9 Cl CF3 B3-84 7.B-6.9 ~m, 128), .~, 4.6-4.3 (M, 3H), 4.0 (M, lH), 3.52 (S, 3H), :'! 1.25 (M, 2H), 1.0-0.7 . (M, 6H).
i. 30 36 S-C(0)0-~ec-C4Hg Cl CF3 78-80 7.7-7.0 (M, 12H), 5.0 M, lH), 4.45 (M, 2H), ~.0 (M, lH), 1.6 (M, .~ 2H), 1.3 (d, 3H), o.g . . . .
; (t, 3H).
'^ 35 . ,' .
~.
:, ... . - . . : : :. .. : ,: .,- , . . . .
: . - . : ~ ~ . . : .
.
: , . .. . . . . .
,i ~ . - . . ,: . i - .: : -- .
,: .- , ; ,::
2(~0~65 EX- Q R3 Rl m.p.C 'H-NMR (S in ppm) ---37 S-C(O)O-6ec-C4Hg Cl Cl 66-69 7.4-6.9 (M, 12H), 5.0 (M, lH), 4.5 (M, 2H), 4.0 (M, lH), 1.6 (M, 2H), 1.28 (d, 3H), 0.9 (M, 3H), ,:
38 C2CH3 Cl CF3 151-154 7.7-7.0 (m, lZH), 4.7 (d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 (s,3H).
39 COCH3 F C~3 157-159 7.7-7.0 (m,12H), 4.7 ; (d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 (s,3H). i`
. .
40 S-N~cH(cH3)2)so2c2H5 Cl CF3 oil 7.65 (m,2H), 7.25 (m,4H), 7.05 (m,lH), 4.6-3.9 (m,3H), 3/65 (m,lH), 3.03 (~,2H), 1.36 (t,3H), 1.24 (d,6H).
.. . .
41 COCB3 Cl CF3 166-168 7.6-7.0 ~m,12H?, 4.7-4.0 (m,3H), 2~3 (s,3H).
..
42 COCH3 F Cl 187-190 7.5-7.~ (m,12H), 4.6 (m,lH), 4.4 ~m,lH), 4.0 (m,lH), 2.26 (6,3H). ,~
~:
.
'' ,.;, ,. :
`~
ZC~ 65 41 ~:
~' ',' 5 EX- Q R3 Rl m.p.C 'H NMR (~ i~ ppm) ~MPLE .
43 COCH3 F Br181-186 7.6-7.0 (m,12H), 4.65 (m,lH~, 4.4 (m,lH), 4.0 (m,lH), 2.25 (~,3H).
44 CO2Me F CF380-86 :
~ 15 45 COPh F CF3176-179 . ~
46 COEt Cl CF3 169-170 . 47 EtCOCO Cl CF3 166-167 , 20 ,, 48 CO-n-9u Cl CF3 60-62 ~, .~^ 49 COCH3 Cl Cl 205-206 ~ A ' ~, , 25 50 COEt Cl Cl lS7-158 :~,~ . , '~ 51 CO2Me Cl Cl 162-166 '.' ~, 52 4-ClPhCO Cl CF3 209-211 ., 30 - 53 t-BuCO Cl CF3 140-145 ;
-. 54 PhOCO Cl CF3 150-155 ' ;:
~ .
r, ''. ' ' :. , ~ . -,, '. '' ~.. ' ` :" ' 2(~)Q~5 Example 55 N-acetyl-3,9-bis(4-chlorophenyl)-4,5-dihydro-N-[9-(trifluoromethyl)phenyl]-lH-pyrazole-l-~_sarboxamide The compound of Step D of E~ample 6 (0.65 9) was dissolved in tetrahydrofuran (20 ml) and treated with 60~ sodium hydride in oil (0.12 9). After the evolution of hydrogen was complete (30 minutes), acetic anhydride (0.6 ml) was added and the mi~ture was stirIed at room temperature for 16 hours. The reaction was diluted with saturated aqueous ammonium chloride solution (15 ml~ and ethyl acetate (30 ml).
The organic layer was dried with magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel with hexanes/ethyl acetate (3:1) as eluent. Addition of methanol (10 ml) to the product gave, after filtration, the title compound (0.4 9). m.p. 166 to 168C.
-~ NMR (CDC13) 7.6-7.0 (m, ArH, 12H), 9.7-4.0 (m, 3H, CH and CH2), 2.3 (s, COCH3, 3H).
.
,, :
,, ', :
,~ : ' .
:~, ,~
,.
'.
' -.
- ,,. -, , ,,: - . . ~, .. ,., . ,, . ~,.. , . .. : . ; -.. - . . ~,. . .,, i, ,,, ~ . : . ;
. . . . .~ . . : . .: :
2~10Q~6S
`: . :
. 43 Table 1 : ':
1~)~N--N ~/~
O ~
~B
:~
'. R2 B R8 Rg 4-CF35-Cl H Me OEt ~ 4-CF35-Cl Me Me OEt .. 20 9-CF3 H CO2Me Me OEt 4-Cl H CO2Me Me OEt ' , 4-Br H CO2Me Me OEt ~,~ 4-OCF3 H CO2Me Me OEt :
`. 4-CF35-Cl CO2Me Me OEt .~ 25 4-C15-Cl C02Me Me OEt ~' 4-OCF35-Cl CO2Me Me OEt .~ 4-CF35-CF3 CO2Me Me OEt 4-CF35-F CO2Me Me OEt 4-CF35-Cl Ph Me OEt 4-CF35-C14-Cl-Ph Me OEt 4-CF35-Cl CO2Et Me OEt - 4-CF35-Cl H Me O-n-Bu 4-CF34-F H Me O-n-Bu 4-CF3 H Me Me O-n-Bu 4-CF35-Cl Me Me O-n-Bu .
; 4-CF35-Br Me Me O-n-Bu ~, , .
,. ~' . .
:.-.......... :
21?Q~i5 :
Rl R2 B R8 Rg :-4-CF3 4-F Me Me O-n-8u 4-CF3 H CV2Me Me O-n-Bu 4-Cl H CO2Me Me O-n-Bu 4-Br H CO2Me Me O-n-Bu 4-OCF3 H CO2Me Me O-n-Bu 4-CF3 5-Cl CO2Me Me O-n-Bu .~ 4-C1 5-Cl CO2Me Me O-n-Bu '.- 4-Br 5-Cl CO2Me Me O-n-Bu -: 4-OCF3 5-Cl CO2Me Me O-n-Bu 4-CF3 5-Br CO2Me Me O-n-Bu 4-C1 5-Br CO2Me Me O-n-Bu ~ 4-Br S-Br CO2Me Me O-n-Bu ;. 4-OCF3 5-Br CO2~e Me O-n-Bu 4-CF3 4-F CO2Me Me O-n-Bu . 20 4-C1 4-F CO2Me Me O-n-Bu 9-Br 4-P C02Me Me O-n-E3u ; 4-OCF3 4-F C02Me Me C)-n-Bu 4-CF3 5-CF3 CO2Me Me O-n-Bu 4-CF3 5-F CO2Me Me O-n-Bu :
4 CF3 5-Cl Ph Me O-n-Bu ~, - 4-CF3 5-C1 4-Cl-Ph Me O-n-Bu 4-CF3 5-Cl CO2Et Me O-n-Bu 4-CF3 5-Cl Me Me O-n-hexyl .~ 4-CF3 H CO2Me Me O-n-hexyl 3 4-Cl H CO2Me Me O-n-hexyl ~: -4-Br H CO2Me Me O-n-hexyl 4-OCF3 H C02Me Me O-n-hexyl 4-CF3 5-Cl C02Me Me O-n-hexyl 4-Cl S-Cl CO2Me Me O-n-hexyl .:
4-Br 5-Cl CO2Me Me O-n-hexyl . ~.
4-OCF3 5-Cl CO2Me Me O-n-hexyl : ::
4-CF3 5-Br CO2Me Me O-n-hexyl .,`1 ..
. . , , ; ' ~.
- .. ~ - ~ : . . ' ., ,: , . . :, , ., , . . ~ . . . . . .. . .. ..
2n~6s Rl R2 B R8 Rg 4-C1 5-Br C02Me Me O-n-he2~yl 4-Br 5-Br CO2Me Me O-n-hexyl 4-OCF3 S-Br CO2Me Me O-n-he~yl q-CF3 4-F CO2Me Me O-n-heJcyl 4-C1 4-F CO2Me Me O-n-hexyl 4-Br 4-F C02Me Me O-n-he:~yl 4-OCF3 4-F CO2Me Me O-D-hexyl 4-CF3 5-CF3 C02Me Me O-n-he~yl 4-CF3 5-F C02Me Me O-n-he2~yl 4-CF3 5-Cl Ph Me O-n-he~yl 9-CF3 5-C1 4-Cl-Ph Me O-n-hexyl 4-CF3 5-Cl CO2Et Me O-n-hexyl 4-CF3 S-Cl Me Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl : 4-Cl H CO2Me Me O-n-octyl 4-Br H CO2Me Me O-n-octyi 4-OCF3 H CO2Me Me O-n-octyl 4-CF3 5-Cl CO2Me Me O-n-octyl 4-Cl S-Cl CO2Me Me O-n-octyl - 4-Br S-Cl CO2Me Me O-n-octyl 4-OCF3 S-Cl CO2Me Me O-n-octyl 4-CF3 S-Br CO2Me Me O-n-octyl 4-C1 5-Br CO2Me Me O-n-octyl ~: 4-Br 5-Br CO2Me Me O-n-octyl 4-OCF3 5-Br CO2Me Me O-n-octyl 4-CF3 4-F CO2Me Me O-n-octyl 4-C1 4-F CO2Me Me O-n-octyl -~ 4-Br 4-F CO2Me Me O-n-octyl 4-OCF3 4-F CO2Me Me O-n-octyl 4-CF3 5-CF3 CO2Me Me O-n-octyl 4-CF3 S-F CO2Me Me O-n-octyl 2~1~Q~S
.
1 R2 B R8 Rg 4-CF35-Cl Ph Me O-n-octyl 4-CF35-C14-Cl-Ph Me O-n-octyl ~-~ 4-CF35-Cl CO2Et Me O-n-octyl 4-CF35-Cl Me Me O-n-decyl -.
4-CF3 H CO2Me Me O-n-decyl . 4-Cl H CO2Me Me O-n-decyl 4-Br H CO2Me Me O-n-decyl 9-OCF3 H CO2Me Me O-n-decyl 4-CF35-Cl CO2Me Me O-n-decyl 4-C15-Cl CO2Me Me O-n-decyl 9-Br 5-Cl CO2Me Me O-n-decyl 4-OCF35-C1 ~2Me Me O-n-decyl 4-CF35-Br CO2Me Me O-n-decyl ;~ 4-C15-Br CO2Me Me O-n-decyl !
4-Br 5-Br CO2Me Me O-n-decyl 4-OCF35-Br CO2Me Me O-n-decyl ~. .
4-CF34-F CO2Me Me O-n-decyl . 4-C14-F CO2Me Me O-n-decyl ~` 4-Br 4-F CO2Me Me O-n-decyl .-, 25 4-OCF34-F CO2Me Me O-n-decyl 4-CF35-CF3 CO2Me Me O-n-decyl 4-CF35-F CO2Me Me O-n-decyl 4-CF~ 5-Cl Ph Me O-n-decyl 4-CF35-C14-Cl-Ph Me O-n-decyl 4-CF35-Cl CO2Et Me O-n-decyl 4-CF35-Cl Me Me O-n-dodecyl . 4-CF3 H CO2Me Me O-n-dodecyl 4-Cl H CO2Me Me O-n-dodecyl 4-Br H CO2Me Me O-n-dodecyl 4-OCF3 H CO2Me Me O-n-dodecyl 4-CF35-Cl CO2Me Me O-n-dodecyl , ' ~.7 . :,`, 2~ Q~65 ;
Rl R2 B R8 Rg 7, 4-C1 5-Cl CO2Me Me O-n-dodecyl 4-Br 5-Cl C02Me Me O-n-dodecyl 4-OCF3 5-Cl CO2Me Me O-n-dodecyl 4-CF3 5-Br CO2Me Me O-n-dodecyl 4-Cl S-Br CO2Me Me O-n-dodecyl 4-Br 5-Br CO2Me Me O-n-dodecyl 4-OCF3 5-Br CO2Me Me O-n-dodecyl 4-CF3 4-F CO2Me Me O-n-dodecyl 4-C1 4-F CO2Me Me O-n-dodecyl 4-Br 4-F CO2Me Me O-n-dodecyl 4-OCF3 4-F CO2Me Me O-n-dodecyl 4-CF3 5-CF3 CO2Me Me O-n-dodecyl 4-CF3 5-F CO2Me Me O-n-dodecyl 4-CF3 5-Cl Ph Me O-n-dodecyl 204 CF3 5-C1 4-Cl-Ph Me O-n-dodecyl 4-CF3 5-Cl CO2Et Me O-n-dodecyl .
4-CF3 5-Cl Me Me O-sec-Bu 4-CF3 H CO2Me Me O-sec-Bu , 4-Cl H CO2Me Me O-sec-Bu 25 4-Br H CO2Me Me O-sec-Bu 4-OCF3 H CO2Me Me O-sec-Bu ~' 4-CF3 5-Cl CO2Me Me O-sec-Bu 4-C1 5-Cl CO2Me Me O-sec-Bu 4-Br 5-Cl CO2Me Me O-sec-Bu 4-OCF3 5-Cl CO2Me Me O-sec-Bu 4-CF3 5-Br CO2Me Me O-sec-Bu 4-C1 5-Br CO2Me Me O-sec-Bu ;, -4-Br 5-Br CO2Me Me O-sec-Bu 4-OCF3 5-Br CO2Me Ne O-sec-Bu 354-CF3 4-F CO2Me Me O-sec-Bu 4-C1 4-F CO2Me Me O-sec-Bu ,.
:
..
- - , .
Æ(~t:)Q16S
..
Rl R2 ~ R8 Rg --4-Br 4-F CO2Me Me O-sec-Bu 4-OCF34-F CO2Me Me O-sec-8u -~ 4-CF35-CF3 CO2Me Me O-sec-Bu 4-CF35-F CO2Me Me O-sec-Bu 4-CF35-CI Ph Me O-sec-Bu 4-CF35-C14-Cl-Ph Me O-sec-Bu 9-CF35-Cl CO2Et Me O-sec-Bu 4-CF35-Cl Me Me OCH2CH2OEt 4-CF3 H COzMe Me OCH2CH2Et 4-Cl H CO2Me Me OCH2CH2Et 4-Br H CO2Me Me OCH2CH2OEt 4-OCF3 H CO2Me Me OCH2CH2OEt " 4-CF35-Cl CO2Me Me OCH2CH2Et 4-C15-Cl c02Me Me OCH2CH2OEt 4-~r 5-Cl CO2Me Me OCH2CH2OEt 4-OCF35-Cl CO2Me Me OCH2CH2OEt 4-CF35-Br CO2Me Me OCH2CH2OEt 4-C15-Br CO2Me Me OCH2CH2OEt i, 4-~r 5-Br CO2Me Me OCH2CH2OEt ", 25 4-OCF35-Br CO2Me Me OCH2CH2OEt ,!~i 4-CF34-F CO2Me Me OCH2CH2Et .. 4-C14-F CO2Me Me OCH2CH2OEt '~ 4-Br 4-F CO2Me Me OCH2CH2OEt 4-OCF34-F CO2Me Me OCH2CH2OEt - 4-CF35-CF3 CO2Me Me QCH2CH2OEt . 4-CF35-F CO2Me Me OCH2CH2OEt 4-CF35-Cl Ph Me OCH2CH2OEt 4-CF35-C14-Cl-Ph Me OCH2CH2OEt 4-CF35-Cl CO2Et Me OCH2CH2OEt 4-CF35-Cl Me Me OCH2CC13 . 4-CF3 H CO2Me Me OCH2CC13 4-Cl H CO2Me Me OCH2CC13 4-Br H CO2Me Me OCH2CC13 , .
' ' ':
, - ~
2~ 65 Rl R2 B R8 Rg .
4-OCF3 H CO2Me Me OCH2CC1 4-CF35-Cl CO2Me Me OCH2CC1 4-C1 5-Cl CO2Me Me OCH2CC1 4-Br 5-Cl CO2Me Me OCH2CC1 ~- 10 4-OCF35-Cl CO2Me Me OCH2CC1 4-CF35-Br CO2Me Me OCH2CC1 4-C1 5-Br CO2Me Me OCH2CC1 4-Br 5-Br CO2Me Me OCH2CC1 4-OCF3 5-Hr CO2Me Me OCH2CC1 4-CF3 4-F CO2Me Me OCH2CC1 4-Cl 4-F CO2Me Me OCH2CC1 4-E~r 4-F C02Me Me OCH2CC1 4-OCF3 4-F CO2Me Me OCH2CC1 4-CF3 5-CF3 CO2Me Me OCH2CC1 9-CF35-F CO2Me Me OCH2CC1 4-CF3 5-Cl Ph Me OCH2CC1 9-CF3 5-C1 4-Cl-Ph Me OCH2CC1 ' 4-CF3 5-Cl CO2Et Me OCH2CC1 9-CF3 5-Cl Me Me OCH2CF3 4-CF3 H CO2Me Me OCH2CF
9-Cl H CO2Me Me OCH2CF3 4-Br H CO2Me Me OCH2CF3 ; 4-OCF3 H CO2Me Me OCH2CF3 4-CF35-Cl CO2Me Me OCH2CF3 ` ,~ 4-C1 5-Cl C02Me Me OCH2CF3 4-Br 5-Cl CO2Me Me OCH2CF3 4-OCF35-Cl CO2Me Me OCH2CF3 : 4-CF35-Br CO2Me Me OCH2CF3 4-C1 5-Br CO2Me Me OCH2CF3 5-Br CO2Me Me OCH2CF3 4-OCF35-Br CO2Me Me OCH2CF3 ~' , .
;,' '' ' 21~Q~65 Rl R2 B R8 Rg 4-CF3 4-F CO2Me Me OCH2CF3 4-C1 4-F CO2Me Me OCH2CF3 4-Br 4-F CO2Me Me OCH2CF3 4-OCF3 4-F CO2Me Me OCH2CF3 4-CF3 5-CF3 CO2Me Me OCH2CF3 4-CF3 5-F CO2Me Me OCH2CF3 4-CF3 5-Cl Ph Me OCH2CF3 4-CF3 5-C1 4-Cl-Ph Me OCH2CF3 ` 4-CF3 5-Cl CO2Et Me OCH2CF3 4-CF3 5-Cl Me Me OCH2CO2Et 4-CF3 H CO2Me Me OCH2CO2Et 4-Cl H CO2Me Me OCH2C2Et 9-Br H CO2Me Me OCH2CO2Et 4-OCF3 H CO2Me Me OCH2CO2Et 4-CF3 5-Cl CO2Me Me OCH2C2Et 4-C1 5-Cl CO2Me Me OCH2CO2Et 4-Br 5-Cl CO2Me Me OCH2CO2Et 4-OCF3 5-Cl CO2Me Me OCH2CO2Et 4-CF3 5-Br CO2Me Me OCH2CO2Et 4-C1 5-Br CO2Me Me OCH2CO2Et 4-Br 5-Br CO2Me Me OCH2CO2Et 4-OCF3 5-Br CO2Me Me OCH2CO2Et 4-CF3 4-F CO2Me Me OCH2CO2Et . 4-C1 4-F CO2Me Me OCH2CO2Et 4-Br 4-F CO2Me Me OCH2CO2Et 4-OCF3 4-F CO2Me Me OCH2C2Et 4-CF3 5-CF3 CO2Me Me OCH2CO2Et 4-CF3 5-F CO2Me Me OCH2CO2Et 4-CF3 5-Cl Ph Me OCH2CO2Et 4-CF3 5-C1 4-Cl-Ph Me OCH2CO2Et 4-CF3 5-Cl CO2Et Me OCH2CO2Et .~'.
... .
' : . ' . . .. . . ... . .. . . ..
~ - .
2n~Q~6s Rl R2 B R8 R9 9-CF3 H H Me F .
4-CF3 5-Cl H Me F
4-CF3 5-Br H Me F
^. 4-CF3 4-F H Me F
4-CF3 H Me Me F
4-CF3 5-Cl Me Me F
4-CF3 5-Br Me Me 4-CF3 4-F Me Me F
4-CF3 H CO2Me Me F
4-Cl H CO2Me Me F
4-~r H CO2Me Me F
~`: 4-OCF3 H C2M~ Me F
4-CF3 5-Cl CO2Me Me F
4-C1 5-Cl CO2Me Me F
4-Br 5-Cl CO2Me Me F
4-OCF3 5-Cl CO2Me Me F
. 4-CF3 5-Br CO2Me Me F
4-C1 5-Br CO2Me Me F
.~ 4-8r 5-Br CO2Me Me F
4-OCF3 5-Br CO2Me Me F
4-CF3 4-F CO2Me Me F
4-C1 4-F CO2Me Me F
4-Br 4-F CO2Me Me F
4-OCF3 4-F CO2Me Me F :
` 30 4-CF3 S-CF3 CO2Me Me F
.~ 4-CF3 5-F CO2Me Me F
4-CF3 5-Cl Ph Me F
. 4-CF3 5-C1 4-Cl-Ph Me F -`
4-CF3 5-Cl CO2Et Me F :
4-CF3 5-Cl CO2Me Me piperidino . 4-CF3 4-F Me Me piperidino 4-CF3 Cl CO2Me Me morpholino .
, ' .' .. . .
: , .
2~ 6S
Rl R2 B R8 Rg --4-OCF3 Cl CO2Me Me morpholino 4-CF3 S-Cl CO2Me Me n-Pr 4-OCF3 5-Cl CO2Me Me n-Pr 4-CF3 5-Br CO2Me Me sec-Bu 4-C1 5-Br CO2Me Me ~ec-Bu 4-Elr 5-Br CO2Me Me sec-Bu 4-OCF3 5-Br CO2Me Me sec-Bu 4-CF3 4-F CO2Me Me 4-Cl-Ph 4-C1 4-F CO2Me Me 4-Cl-Ph -,: 15 4-Br 4-F CO2Me Me 4-Cl-Ph 4-OCF3 4-F CO2Me Me 4-Cl-Ph ~
4-CF3 5-Cl Me Et OCH2CC13 ~ ~. .
4-CF3 H CO2Me Et NEt2 `~
4-Cl H CO2Me Et NEt2 `
4-Br H CO2Me Et NEt2 4-OCF3 H CO2Me Et NEt2 , 9-CF3 5-Cl CO2Me Et 2,6-di-Me-morpholino ;
4-C1 5-Cl CO2Me Et 2,6-di-Me-morpholino 4-Br S-Cl CO2Me Et 2,6-di-Me-morpholino 4-OCF3 5-Cl CO2Me Et 2,6-di-Me-morpholino 4-CF3 5-Cl Me iPr OEt 4-CF3 H CO2Me iPr OEt 4-Cl H CO2Me iPr OEt 4-Br H CO2Me iPr OEt 4-OCF3 H CO2Me iPr OEt 4-CF3 5-Cl CO2Me iPr OEt 4-C1 5-Cl CO2Me iPr OEt ;
4-Br S-Cl CO2Me iPr OEt 4-OCF3 5-Cl CO2Me iPr OEt ...
4 CF3 S-Br CO2Me iPr OEt -4-C1 5-Br CO2Me iPr OEt :
~ .
,~. . . . .
~?0~65 . Rl R2 B R8 Rg 4-Br 5-Br CO2Me iPr OEt 4-OCF3 5-Br CO2Me iPr OEt 4-CF3 4-F CO2Me iPr OEt 4-C1 4-F CO2Me iPr OEt 104-E~r 9-F CO2Me iPr OEt .~ 4-OCF3 4-F CO2Me iPr OEt 4-CF3 5-CF3 CO2Me iPr OEt 4-CF3 5-F CO2Me iPr OEt 4-CF3 5-Cl Ph iPr OEt 4-CF3 5-C1 4-Cl-Ph iPr OEt 4-CF3 5-Cl C02Et iPr OEt 4-CF3 5-Cl CO2Me Me ON~(CH3)SCH3 4-CF3 5-Cl CO2Me Me 2,3-dihydro-2,2-dimethylbenzofuranyl 2û oxy-7 4-CF3 5-Cl CO2Me Me l-naphtho~y -~ 4-CF3 5-Cl Me iPr O-n-Bu 4-CF3 H CO2Me iPr O-n-Elu 4-Cl H CO2Me iPr O-n-Bu .~ 25 4-Br H CO2Me iPr O-n-Bu -4-OCF3 H CO2Me iPr O-n-Bu 4-CF3 5-Cl CO2Me iPr O-n-Bu :
. 4-C1 5-Cl CO2Me iPr O-n-Bu 4-Br 5-Cl CO2Me iPr O-n-Bu ~; 30 4-OCF3 5-Cl CO2Me iPr O-n-Bu 4-CF3 5-Br CO2Me iPr O-n-Bu 4-C1 5-Br CO2Me iPr O-n-Bu : 4-Br 5-Br CO2Me iPr O-n-Bu 4-OCF3 5-Elr CO2Me iPr O-n-Bu 4-CF3 4-F CO2Me iPr O-n-Bu 4-C1 4-F CO2Me iPr O-n-Bu 4-Br 4-F CO2Me iPr O-n-Bu ',';
:
; ; ~:' ' 2~Q~6S
.
Rl R2 E3 R8 Rg 5 . - . ._ .
4-OCF3 4-F CO2Me iPr O-n-Bu 4-CF3 5-CF3 CO2Me iPr O-n-Bu ~.
4-CF3 5-F CO2Me iPr O-n-Bu ~ f 4-CF3 5-Cl Ph iPr O-n-Bu 10 4-CF3 5-C1 4-Cl-Ph iPr O-n-Bu `
4-CF3 5-Cl CO2Et iPr O-n-Bu 4-CF3 H CO2Me iPr OCH2CO2Me .:
4-CF3 5-Cl CO2Me iPr OCH2CO2Me 4-CF3 5-Br CO2Me iPr OCH2CO2Me - 15 4-CF3 4-F CO2Me iPr OCH2CO2Me ~:~ 4-CF3 H CO2Me iPr NMe2 :~ 4-Cl H CO2Me iPr NMe2 4-Br H CO2Me iPr NMe2 9-OCF3 H CO2Me iPr NMe2 20 4-CF3 S-Cl CO2Me iPr NEt2 .) 4-C1 5-Cl CO2Me iPr NEt2 4-~r 5-Cl CO2Me iPr NEt2 4-OCF3 5-Cl CO2Me iPr NEt2 .
q 4-CF3 5-Br CO2Ne iPr piperidino ; 25 4-C1 5-~r CO2Me iPr piperidino :
4-13r 5-BI CO2Me iPr piperidino 4-OCF3 5-Br CO2Me iPr piperidino ~ -4-CF3 4-F CO2Me iPr Et 4-C1 4-F CO2Me iPr Et . .
: 30 4-Br 4-F CO2Me iPr Et ~: 4-OCF3 4-F CO2Me iPr Et .. ~ 4-CF3 H H CH2Ph OEt .. 4-CF3 5-Cl H CH2Ph O-n-oc'cyl 4-CF3 5-Br H CH2Ph S:)CH2C02Et . :
35 4-CF3 H Me CH2Ph ~Et2 ., ,~:
.
:.:
," . : . . .. ~.'''.1 . .. :
ZC-OQ~65 Rl R2 B R8 Rg 4-CF35-Cl Me CH2Ph morpholino 4-CF35-~r Me CH2Ph 4-Cl-Ph 4-CF34-F Me CH2Ph Et 4-CF3 H CO2Me CH2Ph O-n-Bu ; 10 4-Cl H CO2Me CH2Ph O-iPr 4-~r H CO2Me CH2Ph OCH2CF3 4-OCF3 H CO2Me CH2Ph NMe2 4-CF35-Cl CO2Me CH2Ph piperidino 4-C15-Cl C02Me CH2Ph Ph 4-Br 5-Cl CO2Me CH2Ph 4-NO2-Ph 4-OCF35-Cl CO2Me CH2Ph Bu 4-CF35-Br CO2Me CH2Ph O-n-he~yl ; 4-C15-Br C02Me CH2Ph O-sec-Bu 4-Br 5-Br C02Me Q2ph OCH2CH20Et 4-OCF35-Br CO2Me CH2Ph NMe2 4-CF34-F CO2Me CH2Ph 2,6-di-Me-morpholino .: 4-C14-F CO2Me CH2Ph 3-Br-Ph 4-Br 4-F CO2Me CH2Ph 4-Me-Ph 4-OCF34-F CO2Me CH2Ph nPr i 25 4-CF35-CF3 CO2Me CH2Ph Me : 4-CF35-F CO2Me CH2Ph OEt 4-CF35-Cl Ph CH2Ph O-n-Bu 4-CF35-C14 Cl-Ph CH2Ph O-n-octyl 4-CF35-Cl C02Et CH2Ph OCH2ccl3 ~n .
'.
, ;2~)Q~65 ~aLl~_Z
N--N ~R, )7--N o S-N-S-Rg l S R,~ O
. :.
", '. :,.
,, - ,.:
Rl R2 B R8 Rg ::
;: 4-CF3 H CO2Me Me NMe2 4-Cl H CO2Me Me NMe2 .:i 4-Br H CO2Me Me NMe2 . - 25 4-OCF3 H CO2Me Me NMe2 4-CF3 5-Cl CO2Me Me NMe2 1; 4-Cl S-Cl CO2Me Me NMe2 ,` 9-Br 5-Cl CO2Me Me NMe2 4-OCF3 5-Cl CO2Me Me NMe2 :
304-CF3 5-Br CO2Me Me NMe2 9-C1 5-Br CO2Me Me NMe2 4-Br 5-Br CO2Me Me NMe2 .
` 4-OCF3 5-Br CO2Me Me NMe2 4-CF3 4-F CO2Me Me NMe2 ::
354-C1 4-F CO2Me Me NMe2 , :, ~
: ..
2~ 65 ~7 . Rl R2 9 R8 Rg 4-~r 4-F CO2Me Me NMe2 4-OCF34-F CO2Me Me NM~2 4-CF35-CF3 CO2Me Me NMe2 4-CF35-F CO2Me Me NMe2 4-CF35-Cl Ph Me NMe2 9-CF35-C14-Cl-Ph Me NMe2 : 4-CF35-Cl CO2Et Me NMe2 4-CF3 H CO2Me Me NEt2 4-Cl H CO2Me Me NEt2 4-Br H CO2Me Me NEt2 4-OCF3 H CO2Me Me NEt2 4-CF35-Cl CO2Me Me NEt2 9-C15-Cl co2Me Me NEt2 4-Br 5-Cl co2Me Me NEt2 4-OCF35-Cl CO2Me Me NEt2 4-CF35-Br CO2Me Me NEt2 4-C15-Br CO2Me Me NEt2 4-Br 5-Br CO2Me Me NEt2 4-OCF35-Br CO2Me Me NEt2 :~ 25 4-CF34-F CO2Me Me NEt2 4-C14-F CO2Me Me piperidino 4-Br 4-F CO2Me Me piperidino 4-OCF34-F CO2Me Me piperidino 4-CF35-CF3 CO2Me Me piperidino '~0 4-CF35-F CO2Me Me piperidino 4-CF35-Cl Ph Me piperidino 4-CF35-C14-Cl-Ph Me piperidino 4-CF35-Cl CO2Et Me piperidino 4-CF3 H CO2Me Me C2~5 4-CF35-Cl CO2Me Me C2H5 4-CF35-Br CO2Me Me C2H5 4-CF34-F CO2Me Me C2H5 .
. .
, ., . .
2C~ fiS
Rl R2 B R8 Rg 4-CF3 H C02Me Me n-he2cyl 4-Cl H C02Me Me n-he~yl 4-Br H C02Me Me n-he~yl .
4-OCF3 H CO2Me Me rl-hexyl 4-CF3 5-Cl CO2Me Me Ph 9-C1 5-Cl CO2Me Me Ph ~.
:: 4-Br 5-Cl CO2Me Me Ph 4-OCF3 5-Cl CO2Me Me Ph 4-CF3 5-EIr CO2Me Me 4-Cl-Ph 4-C1 5-Br CO2Me Me 4-Cl-Ph 4-Br 5-Br CO2Me Me 4-Cl-Ph 4-OCF3 5-Br CO2Me Me 4-Cl-Ph 4-CF3 4-F CO2Me Me 4-Me-Ph 4-C1 4-F CO2Me Me 4-Me-Ph 4-Br 4-F CO2Me Me 4-Me-Ph 4-OCF3 4-F CO2Me Me 4-Me-Ph 4-CF3 5-CF3 CO2Me Me n-Bu ~ 4-CF3 5-F CO2Me Me n-Bu ,; 4-CF3 S-Cl Ph Me n-Bu ;
. 25 4-CF3 5-C1 4-Cl-Ph Me n-Bu ~:
4-CF3 5-Cl CO2Et Me n-Bu 4-CF3 H H Et NMe2 .
4-CF3 5-Cl H Et NMe2 4-CF3 5-E~r H Et NMe2 4-CF3 4-F H Et NMe2 4-CF3 H Me Et NEt2 4-CF3 5-Cl Ne Et NEt2 4-CF3 5-Br Me Et NEt2 . 4-CF3 4-F Me Et NEt2 4-CF3 5-Cl CO2Me Et morpholino 4-C1 5-Cl CO2Me Et morpholino 4-Br 5-Cl CO2Me Et morpholino 4-OCF3 5-Cl CO2Me t morpholino ' , ',~
,' ' ,''.
. , . . :
2~?~Q~L65 , .
. :
1 R2 B R8 Rg 4-CF3 S-Cl CO2Me Et iPr 4~C1 5-Cl CO2Me Et iPr 4-Br 5-Cl CO2Me Et iPr 4-OCF3 5-Cl CO2Me Et iPr 4-CF3 5-Br C02Me Et n-Bu 4-C1 5-Br CO2Me Et n-Bu ; 4-Br 5-Br CO2Me Et n-Bu 4-OCF3 5-Br CO2Me Et n-Bu 4-CF3 4-F CO2Me Et Ph : 15 4-C1 4-F CO2Me Et Ph 4-Br 9-F CO2Me Et Ph 4-OCF3 4-F CO2Me Et Ph 4-CF3 H CO2Me iPr NMe2 4-Cl H CO2Me iPr NMe2 4-Br H CO2Me iPr NMe2 4-OCF3 H CO2Me iPr NMe2 4-CF3 5-Cl CO2Me iPr NMe2 ~ 4-C1 5-Cl CO2Me iPr NMe2 :
:.' 4-Br 5-Cl CO2Me iPr NMe2 ~: 25 4-OCF3 5-Cl CO2Me iPr NMe2 4-CF3 5-Br .CO2Me iPr NMe2 4-C1 5-Br CO2Me iPr NMe2 4-Br 5-Br CO2Me iPr NMe2 4-OCF3 5-Br CO2Me iPr NMe2 4-CF3 4-F CO2Me iPr NMe2 4-C1 4-F CO2~e iPr NMe2 4-Br 4-F CO2Me iPr NMe2 ' 4-OCF3 4-F CO2Me iPr NMe2 `I 4-CF3 5-CF3 CO2Me iPr NMe2 4-CF3 S-F CO2Me iPr NMe2 ' 4-CF3 5-Cl Ph iPr NMe2 4-CF3 5-C1 4-Cl-Ph iPr NMe2 4-CP3 5-Cl CO2Et iPr NMe2 , .
;
.. .
,, :
2(~ ''165 : .
Rl R2 ~ R8 Rg 4-CF3 H CO2Me iPr2, 6-di-Me-morpholino 4-CF35-Cl CO2Me iPr 2,6-di-Me-morpholino 4-CF35-Br CO2Me iPr 2,6-di-Me-morpholino 4-CF34-F CO2Me iPr 2,6-di-Me-morpholino 4-CF3 H CO2Me iPr piperidino : 4-OCF3 H CO2Me iPr piperidino 4-CF35-Cl CO2Me iPr Et 4-Cl S-Cl CO2Me iPr Et ~ 4-Br 5-Cl CO2Me iPr Et ~-: 15 4-OCF35-Cl CO2Me iPr Et 4 CF35 Br CO2Me iPr n-Bu 9-C15-Br CO2Me iPr n-Bu 4-Br 5-Br CO2Me iPr n-Bu 4-OCF35-Br CO2Me iPr n-Bu ~ 20 4-CF34-F CO2Me iPr . Ph ; q-Cl 9-F CO2Me iPr Ph ; 4-Br 4-F CO2Me iPr Ph 4-OCF34-F CO2Me iPr Ph 4-CF35-CF3 CO2Me iPr 4-Cl-Ph 4-CF35-F CO2Me iPr 4-Cl-Ph 4-CF35-Cl Ph iPr 4-Cl-Ph 4-CF35-C14-Cl-Ph iPr 4-Cl-Ph 4-CF35-Cl CO2Et iPr 4-Cl-Ph '.
~-., ~ .
-. .
~ .:
, , . . ~ , , .
., Table ~
.
-N-N
N
o 1 11 S-N-P-Y Rlo R~Y R1~
~ . .
: .
~- Rl R2 B R8 Y' Y'Rl~ Y Rll . . ._ ---- .
4-CF3 H CO2Me tBu S OEt OEt i 20 4-Cl H CO2Me tBu S OEt OEt ' 4-Br H CO2Me tBu S OEt OEt ~, 4-OCF3 H CO2Me tBu S OEt OEt .~ 4-CF3 5-Cl CO2Me tBu S OEt OEt ; 4-C1 5-Cl CO2Me tBu S OEt OEt ', 25 4-Br 5-Cl CO2Me tBu S OEt OEt , 4-OCF3 5-Cl CO2Me tBu S OEt OEt "~ 4-CF3 5-Br CO2Me tBu S OEt OEt . 4-C1 5-Br CO2Me tBu S OEt OEt 4-Br 5-8r CO2Me tBu S OEt OEt ` 3û 4-OCF3 5-Br CO2Me tBu S OEt OEt 4-CF3 4-F CO2Me tBu S OEt OEt 4-C1 4-F CO2Me tBu S OEt OEt . 4-Br 4-F CO2Me tBu S OEt OEt ;:. 4-OCF3 4-F CO2Me tBu S OEt OEt ~ 35 4-CF3 5-CF3 CO2Me tBu S OEt OEt :~ 4-CF3 5-F CO2Me tBu S OEt OEt 4-CF3 5-Cl Ph tBu S OEt OEt ,,, :.
.. . . . .
;. .;
., , , . . , ., . ;.: ,.. .: . .. : .:.. . .. :. . ~ .. ,, .. :. . ..... , . :
2~?U~65 ~ 62 . ,: .
.~ .
Rl R2 B R8 Y Y'Rlo Y Rll - .
., .
4-CF3 5-C1 4-Cl-Ph tBu S OEt OEt 4-CF3 5-Cl CO2Et t~u S OEt OEt 4-CF3 H CO2Me tBu S OCH2c(Me)2cH2O
4-Cl H CO2Me tBu S OCH2C(Me)2CH2O
4-Br H CO2Me tBu S OCH2C(Me)2CH2O
4-OCF3 H CO2Me tBu S OCH2c(Me)2cH2O
; 4-CF3 5-Cl CO2Me tBu S OCH2c(Me)2cH2O
4-C1 5-Cl CO2Me tBu S OCH2c(Me)2cH2O
~ 15 4-Br 5-Cl CO2Me tBu S OcH2c(Me)2cH2o " 4-OCF3 5-Cl CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me tBu S OCH2C(Me)2CH2O
: 4-C1 5-Br CO2Me tBu S OC~2C(Me)2CH2O
4-Br 5-Br CO2Me tBu S OCH2C(Me)2CH2O
; 20 4-OCF3 5-Br CO2Me tBu S OCH2C(Me)~CH2O
4-CF3 4-F CO2Me tBu S OCH2C(Me)2CH2O
. 4-C1 4-P CO2Me tBu S OCH2C(Me)2CH2O
4-Br 4-F CO2Me tBu S OCH2c(Me)2cH2O
.~ 4-OCF3 4-F CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 5-CF3 CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 S-F CO2Me tBu S OCH2C(Me)2CH2O
, 4-CF3 5-Cl Ph tBu S OCH2C(Me)2cH2o ' 4-CF3 5-C1 4-Cl-Ph tBu S OCH2C(Me)2CH2O
,~ 4-CF3 5-Cl CO2Et tBu S OCH2c(Me)2cH2O
4-CF3 H CO2Me tBu S OCH2CH2CH2O
: 4-C~ ~ C2~e tBu S OCH2CH2CH2O
4-~r H CO2Me tBu S OCH2CH2CH2O
4-OCF3 H CO2Me tBu S OCH2CH2C~2O
4-CF3 5-Cl C2~e tBu S OCH2cH2cH2O
4-C1 5-Cl CO2Me tBu S OcH2cH2cH2o 4-Br 5-Cl CO2Me tBu S OcH2cH2cH2o 4-OCF3 5-Cl CO2Me tBu S OcH2cH2cH2o ., ~A .
Z(~ 65 Rl R2 B RU Y Y'Rlo Y Rll 4-CF35-Br CO2Me tBu S OCH2CH2CH20 4-C1 5-Br CO2Me tBu S OCH2CH2CH20 4-Br 5-Br C02Me tBu S OCH2CH2CH20 4-OCF3 5-Br CO2Me tBu S OCH2CH2CH20 4-CF3 4-F CO2Me tBu S OCH2CH2CH20 4-C1 4-F CO2Me tBu S OCH2CH2CH20 4-Br 4-F CO2Me tBu S OCH2CH2CH20 4-OCF3 4-F CO2Me tBu S OCH2CH2CH20 4-CF3 5-CF3 CO2Me tBu S oCH2CH2CH20 4-CF3 5-F CO2Me tBu S OCH2CH2CH20 4-CF3 5-Cl Ph tBu S OCH2CH2CH20 4-CF35-~1 4-Cl-Ph tBu S OCH2CH2CH20 4-CF35-Cl C02Et tBu S OCH2Q2CH20 4 -CF3 H CO2Me tBu S CH2cH2 4-Cl H CO2Me tBu S OCH2CH20 :
4-Br H CO2Me tBu S OCH2CH2 . 4-OCF3 H CO2Me tBu S CH2cH2 4-CF3 5-Cl CO2Me tBu S CH2cH2 4-C1 5-Cl CO2Me tBu S CH2cH2 4-Br 5-Cl CO2Me tBu S CH2cH2 4-OCF3 5-Cl CO2Me tBu S OCH2CH20 4-CF3 5-Br C02Me tBu S CH2cH2 4-C1 5-Br CO2Me tBu S OCH2CH20 . 30 4-Br 5-Br CO2Me tBu S CH2cH2 4-OC~3 5-Br C02Me tBu S CH2cH2 !:~
4-CF3 4-F CO2Me tBu S CH2cH2 4-C1 4-F CO2Me tBu S CH2cH2 ~' 4-Br 4-F C02Me tBu S ~CH2cH2 9-OCF3 4-F CO2Me tBu S OCH2CH20 .
4-CF3 5-CF3 CO2Me tBu S CH2cH2 4-CF3 5-F C02Me tBu S OCH2CH20 : -' ..
.: ~ , ' .. . . : -: .. .
. :; :: ~. : ~
2~()Q'~65 Rl R2 B R8 Y Y'Rlo Y Rll 4-CF3 5-Cl Ph tBu S CH2cH2 4-CF3 5-C1 4-Cl-Ph tBu S OCH2CH2 4-CF3 5-Cl CO2Et t~u S OCH2 Q2 4-CF3 H CO2Me iPr S OEt OEt 4-Cl H CO2Me iPr S OEt OEt 4-8r H CO2Me iPr S OEt OEt 4-OCF3 H CO2Me iPr S OEt OEt .~ 4-CF3 5-Cl CO2Me iPr S OEt OEt 4-C1 5-Cl CO2Me iPr S OEt OEt 4-Br 5-Cl CO2Me iPr S OEt OEt 4-OCF3 5-Cl CO2Me iPr S OEt OEt 9-CF3 5-Br CO2Me iPr S OEt OEt 4-C1 5-Br CO2Me iPr S OEt OEt : 20 4-Br 5-Br CO2Me iPr S OEt OEt 4-OCP3 5-Br CO2Me iPr S OEt OEt 4-CF3 4-F CO2Me iPr S OEt OEt 4-C1 4-F CO2Me iPr S OEt OEt 4-Br 4-F CO2Me iPr S OEt OEt : 25 4-OCF3 4-F CO2Me iPr S OEt OEt :
4-CF3 5-CF3 CO2Me iPr S OEt OEt 4-CF3 5-F CO2Me iPr S OEt OEt 4-CF3 5-Cl Ph iPr S OEt OEt ~' 4-CF3 5-C1 4-Cl-Ph iPr S OEt OEt 4-CF3 5-Cl CO2Et iPr S OEt OEt 4-C~3 H CO2Me iPr S OCH2c(Me)2cH2O
4-Cl H CO2Me iPr S OCH2C(Me)2cH2o 4-~r H CO2Me iPr S OCH2C(Me)2cH2o 4-OCF3 H CO2Me iPr S OCH2C~Me)2cH2O
3S 4-CF3 5-Cl CO2Me iPr S OcH2c(Me)2cH2o 4-C1 5-Cl CO2Me iPr S OCH2C(Me)2cH2O
., "
''' ' '.
:- ' ~ : ~: . :
' '. ' ' . , . ' . : .
2~ 65 Rl R2 B R8 Y Y'Rlo Y'R
. ~.
4-13r 5-Cl C02Me iPr S OCH2C(Me)2CH20 4-OCF3 S-Cl CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me iPr S OCH2C(Me)2CH2O
:~ 10 4-C1 5-Br CO2Me iPr S OCH;~C(Me)2CH20 q-Br 5-Br CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 5-Br CO2Me iPr S OCH2c(Me)2cH2O
;~ 4-CF3 4-F CO2Me iPr S OCH2C~Me)2CH2O
4-Cl 9-F CO2Me iPr S OCH2C(Me)2CH2O
4-Br 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 4-F CO2Me iPr S OcH2c(Me)2cH2o 4-CF3 5-CF3 CO2Me iPr S - OCH2C(Me) 2CH2O
4-CF3 5-F CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-Cl Ph iPr S OCH2c(Me)2cH2O
4-CF3 5-C1 4-Cl-Ph iPr S OCH2c(Me)2Q2O
4-CF3 5-Cl CO2Et iPr S OCH2c(Me)2cH2O
4-CF3 H CO2Me Me S OEt OEt 4-Cl H CO2Me Me S OEt OEt 4-Br H CO2Me Me S OEt OEt 4-OCF3 H CO2Me Me S OEt OEt . 4-CF3 S-Cl CO2Me Me S OEt OEt~i 4-Cl S-Cl CO2Me Me S OEt OEt :.`' 4-Br S-Cl CO2Me Me S OEt OEt 4-OCF3 S-Cl CO2Me Me S OEt OEt.
4-CF3 5-Br CO2Me Me S OEt OEt 4-C1 5-Br CO2Me Me S OEt OEt 4-Br 5-Br CO2Me Me S OEt OEt::.
;,. 4-OCF3 S-Br CO2Me Me S OEt OEt :
. 4-CF3 4-F CO2Me Me S OEt OEt 4-C1 4_~ CO2Me Me S OEt OEt ` 4-Br 4-F CO2Me Me S OEt OEt 4-OCF3 4-F CO2Me Me S OEt OEt 4-CF3 5-CF3 CO2Me Me . S OEt OEt ~,~, , , - ,:' .
" .
..
2~ 65 Rl R2 El R8 Y y'R10 Y Rll S
4-CF3 5-F CO2Me Me S OEt OEt 4-CF3 5-Cl Ph Me S OEt OEt 4-CF3 5-C1 4-Cl-Ph Me S OEt OEt 4-CF3 H CO2Me tBu O OEt OEt 4-Cl H CO2Me tBu O OEt OEt .; 4-~r H CO2Me tBu O OEt OEt 4-OCF3 H CO2Me tBu O OEt OEt ; 4-CF3 5-Cl CO2Me tBu O OEt OEt 4-C1 5-Cl CO2Me tBu O OEt OEt 4-Br 5-Cl CO2Me tBu O OEt OEt :
4-OCF3 5-Cl CO2Me tBu O OEt OEt 4-CF3 5-Br CO2Me tBu O OEt OEt 4-C1 5-Br CO2Me tBu O OEt OEt .
4-Br 5-Br CO2Me tBu O OEt OEt 4-OCF3 5-Br CO2Me tBu O OEt OEt 4-CF3 4-F CO2Me tBu O OEt OEt ~:; 4-C1 4-F CO2Me tBu O OEt OEt 4-Br 4-F CO2Me tBu O OEt OEt 4-OCF3 4-F CO2Me tBu O OEt OEt 4-CF3 5-CF3 CO;!tqe tBu O OEt OEt ..
4-CF3 5-F CO2Me tBu O OEt OEt 9-CF3 S-Cl Ph tBu O OEt OEt 4-CF3 5-C1 4-Cl-Ph tBu O OEt OEt 4-CF3 5-Cl CO2Et tBu O OE:t OEt 4-CF3 ~3 CO2Me tBu O OCH2C(Me)2CH20 4-Cl H CO2Me tBu O OCH2C(Me)2cH2o 4-Br H C02Me tl3u o .0CH2C(Me)2CH20 4-OCF3 H CO2Me tBu O OCH2C(Me)2cH2o 4-CF3 5-Cl CO2Me tBu O OCH2C(Me)2cH2o 4-C1 5-Cl CO2Me tE~u O OCH2C(Me)2cH2 ... .
,~
, ~ .
;i .
2~Q~65 Rl R2 B R8 Y Y'Rlo Y R
4-Br 5-Cl CO2Me tBu O OCH2C(Me)2CH2O
4-OCF3 5-CI CO2Me tBu O OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me tBu O OCH2C(Me)2cH2o 4-C1 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-Br S-Br CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 S-Br CO2Me tBu O OCH2C(Me)2cH2o 4-CF3 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-C1 4-F CO2Me tBu O OCH2C(Me)2CH2O
: 15 4-Br 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 4-F CO2Me tBu O OCH2C(Me)2cH2o :~ 4-CF3 5-CF3 CO2Me tBu O OCH2C(Me)2Q 2o 4-CF3 5-F CO2Me tBu O OCH2C(Me)2CH2O
4-CF3 5-Cl Ph tBu O OCH2C(Me)2CH2O
4-CF3 5-C1 4-Cl-Ph tBu O OCH2C(Me)2cH2o . 4-CF3 5-Cl CO2Et tBu O OCH2C(Me)2cH2o :
~' .
,, ~ 3C
~ .
;:~ , ......
~`"
. ~.
. .~, .
. ~ . . . , . . . . .. .- . : . . . .
2C~G~65 6~
Table 4 .
N-~ ~ R~
~, ,Y, S-N-P-Y R
- 15 l l R R
, !
Rl R2 B R8 Y Rlo Y ~11 . -..
4-CF3 H CO2Me iPr O Et OEt ,i, 4-Cl H CO2Me iPr O Et OEt ~;, 25 4-Br H CO2Me iPr O Et OEt 4-OCF3 H CO2Me iPr O Et OEt 4-CF3 5-Cl CO2Me iPr O Et OEt , 9-C1 5-Cl CO2Me iPr O Et OEt ; 4-Br 5-Cl CO2Me iPr O Et OEt ` 30 9-OCF3 5-Cl CO2Me iPr O Et OEt , 4-CF3 5-Br CO2Me iPr O Et OEt 4-C1 5-~r CO2Me iPr O Et OEt 4-Br 5-Br CO2Me iPr O Et OEt 1 4-OCF3 5-Br CO2Me iPr O Et OEt - 35 4-CF3 4-F CO2Me iPr O Et OEt ,.. .
/~
2C~ ÇiS
Rl R2 B R8 Y' Rlo Y Rll :
` 4-C14-F CO2Me iPr O Et OEt 4-Br 4-F CO2Me iPr O Et OEt 4-OCF34-F CO2Me iPr O Et OEt ! :
4-CF35-CF3 CO2Me iPr O Et OEt 4-CF35-F CO2Me iPr O Et OEt 4-CF35-Cl Ph iPr O Et OEt 4-CF35-C14-Cl-Ph iPr O Et OEt 4-CF35-Cl CO2Et iPr O Et OEt 4-CF3 H CO2Me iPr O Et O-iPr ; 15 4-Cl H CO2Me iPr O Et O-iPr . 4-Br H CO2Me iPr O Et O-iPr 4-OCF3 H CO2Me iPr O Et O-iPr ;, 4-CF35-Cl CO2Me iPr O Et O-iPr 4-C15-Cl CO2Me iPr O Et O-iPr 4-Br 5-Cl CO2Me iPr O Et O-iPr 4-OCF35-Cl CO2Me iPr O Et O-iPr . 4-CF35-Br CO2Me iPr O Et O-iPr .. 4-Cl S-Br CO2Me iPr O Et O-iPr ,~ 4-Br 5-Br CO2Me iPr O Et O-iPr 4-OCF35-Br CO2Me iPr O Et O-iPr 4-CF34-F CO2Me iPr O Et O-iPr ~ .
~; 4-C14-F CO2Me iPr O Et O-iPr 4-Br 4-F CO2Me iPr O Et O-iPr ~ i~.
4-OCF34-F CO2Me iPr O Et O-iPr i~.
`- 30 4-CF35-CF3 CO2Me iPr O Et O-iPr ~, : 4-CF35-F CO2Me iPr O Et O-iPr `~
4-CF35-Cl Ph iPr O Et O-iPr . 4-CF35-C14-Cl-Ph iPr O Et O-iPr 4-CF35-Cl CO2Et iPr O Et O-iPr 4-CF3 H CO2Me iPr O Et OPh -4-Cl H CO2Me iPr O Et OPh "
.,: .. : .. -: - . , ..... .. . . , . -. . .: , . .. , . ., . ,, ~
! ~ . ' -, . . . . , " . .. . . , , , '~ . . . , ' . ., . ' . ,, : .. , . ' . .: , .
~, . . .. .. . . . . .
2~(~C~L65 . Rl R2 B R8 Y' Rlo Y R
_ 4-Br H CO2Me iPr O Et OPh 4-OCF3 H CO2Me iPr O Et OPh : 9-CF35-Cl CO2Me iPr O Et OPh 4-C15-Cl CO2Me iPr O Et OPh 4-Br 5-Cl CO2Me iPr O Et OPh 4-OCF35-Cl CO2Me iPr O Et OPh 4-CF35-~r CO2Me iPr O Et OPh 4-C15-Br CO2Me iPr O Et OPh 4-Br 5-Br CO2Me iPr O Et OPh 4-OCF35-Br CO2Me iPr O Et OPh ; 4-CF34-F CO2Me iPr O Et OPh 4-C14-F CO2Me iPr O Et OPh .. 4-Br 4-F CO2Me iPr O Et OPh 4-OCF34-F CO2Me iPr O Et OPh 4-cF35-cF3 co2Me iPr O Et OPh 4-CF35-F CO2Ne iPr O Et OPh `. 4-CF35-Cl Ph iPr O Et OPh 4-CF35-C14-Cl-Ph iPr O Et OPh 4-CF35-Cl CO2Et iPr O Et OPh 4-Br 4-F CO2Me iPr O Ph OEt 4-OCF34-F CO2Me iPr O Ph OEt ~` 4-CF35-CF3 CO2Me iPr O Ph OEt 4-CF35-F . CO2Me iPr O Ph OEt 4-CF35-Cl Ph iPr O Ph OEt .~ 30 4-CF35-C19-Cl-Ph iPr O Ph OEt 4-CF35-Cl CO2Et iPr O Ph OEt . 4-CF3 H CO2Me tBu O Et OEt 4-Cl H CO2Me tBu O Et OEt : 4-Br H CO2Me tau O Et OEt :' 35 4-OCF3 H CO2Me tBu O Et OEt .~ 4-CF35-Cl CO2Me tBu O Et OEt 4-C15-Cl CO2Me tBu O Et OEt ,.
~:
~Q~65 :
Rl R2 B R8 Y' Rlo Y R
4-Br 5-Cl CO2Me tBu O Et OEt 4-OCF3 S-Cl CO2Me tBu O Et OEt 4-CF35-Br CO2Me tBu O Et OEt 4-Cl S-Br CO2Me tBu O Et OEt 4-Br 5-Br CO2Me tBu O Et OEt 4-OCF35-Br CO~Me tBu O Et - OEt 4-CF34-F CO2Me tBu O Et OEt 4-C1 4-F CO2Me t~u O Et OEt 4-Br 4-F CO2Me tBu O Et OEt 4-OCF34-F CO2Me tBu O Et OEt 4-CF3 5-CF3 CO2Me tBu O Et OEt 4-CF3 5-F CO2Me tBu O Et OEt 4-CF3 5-Cl Ph tBu O Et OEt ~;
4-CF3 5-C1 4-Cl-Ph tBu O Et OEt 4-CF3 5-Cl C02Et tBu O Et OEt ~
4-CF3 H CO2Me tBu O Et O-iPr ~ ~;:
4-Cl H CO2Me tBu O Et O-iPr -Br H CO2Me tBu O Et O-iPr 4-OCF3 H CO2Me tBu O Et O-iPr 4-CF35-Cl CO2Me tBu O Et o-iPr 4-C1 5-Cl CO2Me tBu O Et O-iPr 4-Br 5-Cl CO2Me tBu O Et O-iPr 4-OCF35-Cl CO2Me tBu o Et O-iPr 4-CF35-Br CO2Me tBu O Et O-iPr . 30 Cl 5-Elr C02Me tBu O Et O-iPr 4-Br 5-Br CO2Me tBu O Et O-iPr :
: 4-OCF35-Br CO2Me tBu O Et O-iPr 4-CF34-F CO2Me tBu O Et O-iPr 4-C1 4-F C02Me tElu O Et O-iPr 3~ 4-Br 4-F CO2Me tE~u o Et O-iPr . 4-OCF34-F CO2Me tBu O Et O-iPr ;
4-CF35-CF3 CO2Me tBu o Et O-iPr 4-CF35-F CO2Me tBu O Et O-iPr ;
: ':
.
2~Q~I~S
Rl R2 B R8 Y' Rlo Y R
- 4-CF3 5-Cl Ph tBu O Et O-iPr 4-CF3 5-C1 4-Cl-Ph tBu O Et O-iPr 4-CF3 5-Cl CO2Et tBu O Et O-iPr 4-CF3 H CO2Me tBu S Et OPh 4-Cl H CO2Me tBu S Ph OEt 4-Br H CO2Me t9u S Ph O-iPr 4-OCF3 H CO2Me tBu S Ph OPh 4-Br 5-Br CO2Me iPr S iPr OEt 4-OCF3 5-Br CO2Me iPr S iPr O-iPr 4-CF3 4-F CO2Me iPr S iPr OPh 4-C1 4-F CO2Me iPr S nPr OEt 9-Br 4-F CO2Me iPr S nPr O-iPr 4-OCF3 4-F CO2Me iPr S nPr OPh 4-CF3 5-CF3 CO2Me tBu S Me OEt 4-CF3 5-F CO2Me tBu S Me O-iPr 4-CF3 5-Cl Ph tBu S Me OPh , .
` 4-CF3 5-C1 4-Cl-Ph tBu S Me O-sec-8u 4-CF3 5-Cl CO2Et tBu S Me O-nPr ,~, .
i 25 , i .
.~
:, , .- .. .. . . ..
2~ L65 :.
able 5 . . .
~: 4 ~ .
. ~
f ' .
,'', , . Rl R2 El Rlo R
~ 4-CF3 H CO2Me Et Et ., 4-Cl H CO2Me Et Et 4-Br H C2Me Et Et 4-OCF3 H CO2Me Et Et ~, 4-CF3 5-Cl CO2Me Et Et 4-Cl S-Cl CO2Me Et Et .1 4-Br 5-CI CO2Me Et Et i' 4-OCF3 S-Cl CO2Me Et Et ~ 30 4-CF3 5-Br CO2Me Et Et .~ 4-C1 5-Br CO2Me Et Et ~ 4-Br 5-Br CO2Me Et Et :i 4-OCF3 5-9r CO2Me Et Et .i 4-CF3 4-F CO2Me Et Et .~ .
~..
: . .
'7 .~., 2~!0Q~65 Rl R2 El Rlo Rll 4-C1 4-F CO2Me Et Et 4-Br 4-F CO2Me Et Et 4-OCF3 4-F CO2Me Et Et 4-CF3 5-CF3 CO2Me Et Et 4-CF3 S-F C~2Me Et Et 4-CF3 5-Cl Ph Et Et 4-CF3 5-C1 4-Cl-Ph Ft Et 4-CF3 5-Cl CO2Et Et Et Ç-CF3 5-Cl Ph Ph Ph 4-CF3 5-C1 4-Cl-Ph Ph Ph 4-CF3 5-Cl C2Et Ph Ph . ..
.. ,,, , , , - , ... .. .
.:, . , - . . :. . ..
2~Q~65 .
T~ble 6 N-N ~ R~
~ N :
O S-N-R~
lS
Rl R2 B R8 R12 .
: ' 4-CF3 H CO2Me nBu nBu ':
4-Cl H CO2Me nBu nBu 4-Br H CO2Me nBu nBu 4-OCF3 H CO2Me nBu nBu 4-CF3 5-Cl CO2Me nBu nBu 4-C1 5-Cl CO2Me nBu nBu 4-Br 5-Cl CO2Me nBu nBu 4-OCF3 5-Cl CO2Me nBu nBu 4-CF3 5-Br CO2Me nBu nBu 4-C1 5-Br CO2Me ~Bu DBu ~
4-Br 5-Br CO2Me nBu nBu :, 4-OCF3 5-Br CO2Me nBu nBu 4-CF3 4-F CO2Me nBu nBu : ~ : ... :: :-- .. . - . . . .. ..
- ~ /
2(~Q~L6S
Rl R2 El R8 R12 4-C14-F CO2Me ~Bu nBu 4-Br 4-F CO2Me nSu ~B~
4-QCF34-F CO2Me nBu nBu 4-CF35-CF3 CO2Me nBu nBu 4-CF35-F CO2Me ~Bu ~Bu 4-CF35-Cl Ph nBu n9u 4-CF35-C14-Cl-Ph n8u nBu 4-CF35-Cl CO2E~ nBu nBu 4-CF3 H CO2Me -CH2CH2CH2cH2cH2-4-Cl H CO2Me -CH2CH2CH2cH2cH2-4-Br H CO2Me -CH2CH2CHzcH2cH2~
4-OCF3 H CO2Me -CH2CH2CH2cH2cH2-4-CF35-Cl CO2Me -CH2CH2CH2cH2cH2-4-C15-Cl co2Me -CH2CH2CH2cH2cH2-4-Br 5-Cl co2Me -CH2CH2CH2c~2cH2-4-OCF35-Cl C02Me -CH2CH2~HzCH2cH2 4-CF35-Br CO2Me -CH2CH2CH2cH2cH2-4-C15-Br CO2Me -CH2CH2CH2cH2cH2-4-Br 5-Br CO2Me -CH2CH2CH2cH2cH2-40CF35-8r CO2Me -CN2CH2CH2cH2cH2-4-SF34-F CO2Me -CH2CH2CH2cH2cH2-4-C14-F ~02Me -CH2CH2CH2cH2cH2-4-Br 4-F C02Me -CH2CH2CH2cH2cH2-4-OCF34-F CO2Me -CH2CH2CH2cH2cH2-0 4-CF35-CF3 CO2Me -CH2CH2CH2cH2cH2-4-CF35 F CO2Me -CH2CH2CH2cN2cH2-4-C~35-Cl Ph -CH2CH2CH2cH2cH2-4-~F35-C1 4-Cl-Ph -CH2CH2CH2CH2CH2-4-CF35-Cl C02Et -CH2CH2CH2cH2c~2-4-C~3 H CO2Me -CH2CH20CH2cH2-4-Cl H CO2Me -CH2CH20CH2CH2- ~ :
4-Br H CO2Me -CH2CH20CH2CH2-.
2~ L65 4-OCF3 H CO2Me -CH2CH20cH2cH2-4 CF3 5-Cl CO2Me -CH2CH20CH2CH2-4-C1 5-Cl C02Me -CH2cH20cH2Q2 4-Br 5-Cl C2Me -CHzCH2ClCH2CH2 4-OCF3 5-Cl CO2Me _CH2CH20CH2cH2-4-CF3 5-Br CO2Me -CH2CH20CH2cH2 4-C1 5-Br CO2Me -CHzCH20CH2CH2-4-Br 5-Br COzMe -CH2CH20CH2cH2 4-OCF3 5-Br CO2Me -CH2CH20CH2cH2-4-CF3 4-F CO2Me -CH2CH20CH2cH2-4-C1 4-F CO2Me -CH2CH20CH2CH2 4-Br 4-F CO2Me -CH2CH20CH2cH2-4-OCF3 4-F CO2Me -CH2CH20CH2CH2~
4-CP3 5-CF3 CO2Me -CH2CH20CH2cH2-2 0 4-CF3 5-F CO2Me -CH2CH20CH2cH2-4-CF3 5-Cl Ph -CH2CH20CH2cH2 4-CF3 5-C1 4-Cl-Ph -CH2CH20CH2CH2-4-CF3 5-Cl C02Et -CH2CH2~CH2cH2-4-CF3 H CO2Me -CH2CHMeOCHMeCH2-2 5 4-Cl H C02Me -CHzCHMeOCHMeCH2-4-Br H C02Me -CH2CHMeOCHMeCH2-4-OCF3 H CO2Me -CH2CHMeOCHMeCH2-4-CF3 5-C~ C~2Me -C1~2CHMeOCHMeCH2-4-C1 5-~1 ~2M~ -CH2CHMeOCHMeCN2-3 0 4-Br 5-Cl CO2Me -CH2CHMeOCHMeCH2-4-OCF3 S-Cl CO2Me -CH2CHMeOCHMeCH2-4-CF3 5-Br CO2Me -CH2CHMeOCHMeCH2-4-C1 5-Br CO2Me -CH2CHMeOCHMeCH2-4-~r 5-Br C02Me -CH2CNMeOCHMeCH2 3 5 4-OCF3 5-Br CO2Me -CH2CHMeOCHMeCH2-4-CF3 4-F CO2Me -CH2CNMeOCHMeCH2-. .
2~0Q~65 . Rl R2 B RB R12 4-C14-F C~2Me -cH2cHMeoc~ecH2 4-Br 4-F C02Me -CH2CE~eOC}~eCH2-4-OCF34-F C02M~ -cH2cHMeoc~lMec~2 4-CF35-CF3 CO2Me -CH2CHMeOCHMeCH2-4 CF35 F C02Me -CH2C8MeOCHMeCH2-4-CF35-Cl Ph -CH2CHMeOCHMeCH2-4 CF35 cl 4-Cl-Ph -CH2C~MeOCHMeCH2-4-CF35-Cl CO2Et -CH2CHMeOCHMeCH2-4-CF3 N CO2Me Et c 4-Cl H CO2Me Et cyclo-C6H
4-Br H C02Me Et cYClo-C6H
4-OCF3 H CO2Me Et cyclo-C6H
4-CF35-Cl CO2Me Et cyclo-C
4-C15-Cl co2Me Et c 4-Br 5-Cl C02Me Et cyclo-C6H
4-OCF35-Cl CO2Me Et cyclo-C6H
4-CF35-8r CO2Me Et CYC1-4-C15-Br CO2Me Et c 4-Br 5-Br CO2Me Et Cyclo-c6H
4-OCF35-Br CO2Me Et c 4-CF34-F CO2Me Et c 4-C14-F CO2Me St cyclo-C6H
4-Er 4-F CO2Me Et c 4-OCF34-~ CO2Me Et cyclo-c6Hll q-CF35-CF3 C~2Me Et CYC1~C6Hll . .
4-CF35-F CO2Me Et c 4-CF35-Cl Ph Et c 4-CF35-C14-Cl-Ph Et Cyclo-C6H
4-CF35-Cl C02Et Et Cyclo-c6Hll 4-CF3 H CO2Me iPr CH2CH2C2Et 4-Cl H CO2Me iPr CH2CH2C2Et 4-Br H CO2Me iPr CH2CH2C2Et 2~C~Q~65 -4-OCF3 H CO2Me iPr CH2CH2C2Et 4-CF3 5-ClCO2Me iPr CN2CH2C02Et 4-C1 5-ClCO2Me iPr CH2CH2C2Et 4-Br 5-Cl C~2Me iPr CH2CH2C2Et 4-OCF3 5-CI COzMe iPr C~2CH2C2Et 4 CF3 5 Br C02Me iPr CH2C~2C2Et 4-C1 5-Br C~2Me iPr CH2CH2C2Et 4-Br 5-Br CO2Me iPr CN2CH2C2Et 4-OCF3 5-BrC2Me iPr CH2CH2C2Et 4 CF3 4 FC02Me iPr CH2CH2CO2Et 4-C1 4-FCO2Me iPr CH2CH2C2Et 4-Br 4-FCO2Me iPr CH2CH2C2Et 4-OCF3 4-FCO2Me iPr CH2CH2C02Et 4-CF3 5-CF3CO2Me iPr CH2CH2CO2Et 4-CF3 5-FCO2Ne iPr CH2CB2CO2Et 4-C~3 5-Cl Ph iPr CH2CH2CO2Et 4-CF3 5-C1 4-Cl-Ph iPr CH2CH2~02Et 4-CF3 S-Cl CO2Et iPr CH2CH2C2Et 3n '' ' ' . ' ' ' ' ~\
2~ 6S
~bl~
N-N
Rl R2 B Rlo :
4-CF3 H CO2Me tBu 4-Cl H CO2Me tBu 4-Br H CO2Me tBu 25 4-OCF3 H CO2Me tBu 4-CF3 S-Cl CO2Me tBu 4-C1 5-CI CO2Me tBu 4-Br 5-Cl CO2Me tBu 4-OCF3 5-Cl CO2Me tBu 30 4-CF3 5-Br CO2Me tBu 4-C1 5-Br CO2Me tBu 4-9~ 5-Br CO2Me tBu 4-OCF3 5-Br CO2Me tBu 4-CF3 4-F CO2Me : tBu .~.
35 4-C1 4-F CO2Me tBu .
- - . , . : - . . ~ . :: : . : :: . : . . : : : . - - : . :: ::
2C~Q~65 Rl R2 Rlo '' 4-Br 4-F CO2Me tBu 4-OCF3 4-F CO2Me tBu 4-CF3 5-CF~ CO2Me tBu 4-CF3 5-F CO2Me tBu 4-CF3 5-Cl Ph tBu 4-CF3 5-C1 4-Cl-Ph tBu 4-CF3 S-Cl CO2St tBu 4-CF3 H CO2Me Ph 4-Cl H CO2Me Ph 4-Br H C02Me Ph 4-OCF3 H CO2Me Ph 4-CF3 5-Cl CO2Ne Ph 4-C1 5-Cl CO2Me Ph 4-Br 5-Cl CO2Me Ph 4-OCF3 5-Cl CO2Me Ph 4-CF3 5-~r CO2Me Ph 4-C1 5-Br CO2Me Ph 4-Br 5-Br CO2Me Ph 4-OCF3 5-Br CO2Me Ph 4-CF3 4-F CO2Me Ph 4-C1 4-F CO2Me Ph 4-9r 4-F CO2Me Ph 4-OCF3 4-F CO2Me Ph 4-CF3 5-CF3 CO2Me Ph 4-CF3 5-F CO2Me Ph 4-CF3 5-C~ Ph Ph . ,~
4-CF3 5-Cl 4-Cl-Ph Ph ';
4-CF3 5-Cl C2~t Ph 4-CF3 H CO2Me 4-Cl-Ph 4-Cl H CO2Me 4-Cl-Ph 4-Br H CO2Me 4-Cl-Ph .. - :: ,, . ' ,' : . . ,,. .: ::
Rl R2 B Rlo 4-OCF3 H CO2Me 4-Cl-Ph 4-CF3 5-Cl CO2Me q-Cl-Ph 4-C1 5-Cl CO2Me 4-Cl-Ph 4-Br 5-Cl CO2Me 4-Cl-Ph 4-OCF3 5-Cl CO2Me 4-Cl-Ph 4-CF3 5-Br CO2Me 4-Cl-Ph 4-C1 5-Br CO2Me 4-Cl-Ph 4-Br 5-Br CO2Me 4-Cl-Ph 4-OCF3 5-Br C02Me 4-Cl-Ph 4-CF3 4-F CO2Me 4-Cl-Ph 4-C1 4-F CO2Me 4-Cl-Ph 4-Br 4-F CO2Me 4-Cl-Ph 4-OCF3 4-F CO2Me 4-Cl-Ph 4-CF3 S-CF3 CO2Me 4-Cl-Ph 4-CF3 S-F CO2Me 4-Cl-Ph - : ., . . , . , . . ; . . ... . -. .~ , . . ~ ,, , . , ... ,, . , . ; - :
. .. .. . .. .. . . . . ..
2C~0~65 Table 8 10 ~ N-N
~ N
S -N
R~
Rl R2 B V R8 Rg 4-CF3 5-Br H O Me OEt 4-Cl S-Br H O Me OEt 4-Br 5-Br H O Me OEt 4-OCF3 S-Br H O Me OEt 4-CF3 5-Cl H O Me OEt 4-C1 5-Cl H O Me OEt 4-Br 5-Cl H O Me OEt 4-CF3 5-CF3 H O Me OEt 4-CF3 4-F H O Me OEt 4-CF3 H H O Me OEt 4-CF3 S-Br CO2Me O Me OEt 4-CF3 5-Cl CO2Me O Me OEt 4-CF3 5-CF3 CO2Me O Me OEt 4-CF3 4-F CO2Me O Me OEt 2~ 6S
Rl R2 B V RB Rg -4-CF3 H CO2Me Me OEt 4-CF35-Cl H S Me OEt 4-C15-Cl H S Me OEt 4-Br 5-CI H S Me OEt lD 4-CF35-Br N S Me OEt 4-CF35-F H S Me OEt 4-CF34-Cl H S Me OEt 4-CF34-F H S Me OEt 4-CF3 H H S Me OEt 4-CF35-Cl CO2Me S Me OEt 4-CF35-Br CO2Me S Me OEt 4-CF35-F CO2Me S Me OEt 4-CF39-Cl CO2Me S Me OEt 4-CF34-F CO2Me S Me OEt 4-CF3 H CO2Me S Me OEt 4-CF35-Br H O Me O-n-Bu 4-C15-Br H O Me O-n-Bu 4-Br 5-Br H O Me O-n-Bu 4-OCF35-Br H O Me O-n-Bu 4-CF35-Cl H O Me O-n-Bu 4-C15-Cl H O Me O-n-Bu 4-Br S-Cl H O Ne O-n-Bu 4-CF35-CF3 H O Me O-n-Bu 4-CF34-F H O Me O-n-Bu 4-CF3 H H O Me O-n-Bu 4-CF35-Br CO2Me O Me O-n-Bu 4-CF35-Cl CO2Me O Me O-n-Bu 4-CF35-CF3 CO2Me O Me O-~-Bu 4-CF34-F CO2Me O Me O-n-Bu 4-CF3 H CO2Me Me O-n-Bu 4-CF35-Cl H S Me O-n-Bu 4-C15-Cl H S Me O-n-Bu 2~ 65 Rl R2 B V RB R9 4-8r 5-Cl H S Me O-D-Bu 4-CF35-Br H S Me O-n-Bu 4-CF35-F H S Me O-n-Bu 4-CF34-Cl H S Me O-n-9u 4-CF34-F H S Me O-n-Bu 4-CF3 H H S Me O-D-Bu 4-CF35-Cl CO2Me S Me O-n-Bu 4-CF35-Br CO2Me S Me O-n-Bu 4 CF35 F CO2Me ~ Me O-D-Bu 4-CF34-Cl CO2Me S Me O-n-Bu 4-CF34-F CO2Me S Me O-n-Bu 4-CF3 H CO2Me S Me O-n-Bu 4-CF35-Br H O Me O-n-hexyl 4-C15-Br H O Me O-n-hexyl 4-Br S-Br H O Me O-n-hexyl 4-OCF35-Br H O Me O-n-he~yl 4-CF35-Cl H O Me O-n-hexyl 4-C15-Cl H O Me O-n-hexyl 4-Br 5-Cl H O Me O-n-he~yl 4-CF35-CF3 H O Me O-n-he~yl 4-CF34-F H O Me O-D-he~yl 4-CF3 H H O Me O-n-hexyl 4-CF35-Br CO2Me O Me O-n-he~yl 4-CF35-Cl CO2Me O Me O-n-he~yl 3~ 4~CF35-cF3 CO2Me O Me O-n-he~yl 4-CF34-F CO2Me Me O-n-he~yl 4-CF3 H CO2Me Me O-~-he~yl 4-CF35-Cl H S Me O-n-he~yl 4-C15-Cl H S Me O-n-he~yl 4-Br 5-Cl H S Me O-n-he~yl 4-CF35-Br H S Me O-n-hexyl 4-CF35-F H S Me O-n-he~yl .: ~ . :
: . : -2~ 6S
~6 Rl R2 i3 V RB Rg 4-CF34-Cl H S Me O-n-~exyl 4-CF34-F N S Me O-n-he~yl 4-CF3 H ~ S Me O-n-he~yl 4-CF35-Cl CO2Me S ~e O-n-he~yl 4-CF35-Br CO2Me S Me O-n-hexyl 4-CF35-F CO2Me S Me O-n-hexyl 4-CF34-Cl CO2Me S Me O-n-heryl 4-CF34-F CO2Me S Me O-n-he~yl 4-CF3 H CO2Me S Me O-n-hexyl 4-CF35-Br H O Me O-n-octyl 4-C15-Br H O Me O-n-octyl 4-Br 5-Br H O Me O-n-octyl 4-OCF35-9r H O Me O-n-octyl 4-CF35-Cl H O Me O-n-octyl 4-C15-Cl H O Me O-n-octyl 4-Br 5-Cl H O Me O-n-octyl 4-CF35-CF3 H O Me O-n-octyl 4-CF34-F H O Me O-n-octyl 4-CF3 H H O Me O-n-octyl 4-CF35-Br CO2Me O Me O-n-octyl 4-CF35-Cl CO2Me O Me O-n-octyl 4-CF35-CF3 CO2Me O Me O-n-octyl 4-CF34-F CO2Me O Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl 4-CF35-CI N S Me O-n-octyl 4-C15-Cl H S Me O-n-octyl 4-Br 5-Cl H S Me O-n-octyl 4-CF35-Br H S Me O-n-octyl 4-CF35-F H S Me O-n-octyl 4-CF34-Cl H S Me O-n-octyl 4-CF34-F H S Me O-n-octyl 4-CF3 H N S Me O-n-octyl .
. . .
' , . . , ~. : - . : . : ~ . ~ - : .
.: .. , . . , . . , ~.. , :.. .... . , : :
Z~ 65 Rl R2 ~ V R8 R9 4-CF35-Cl CO2Me S Me O-n-~ctyl 4-CF35-~r CO2Me S Me O-n-octyl 4 CF35 F C2Me S Me O-n-octyl 4-CF34-Cl CO2Me S Me O-D-~tyl 4 CF34 F C2Me S Me O-n-octyl 4-CF3 H CO2Me S Me O-n-octyl 4-CF35-Br H O Me O-n-decyl 4-C35-Br H O Me O-n-decyl ~-Br 5-Br H O Me O-n-decyl 4-OCF35-Br H O Me O-n-decyl 4-CF35-Cl H O Me O-n-decyl 4-C15-Cl H O Me O-n-decyl 4-Br 5-Cl H O Me O-n-decyl 4-CF35-CF3 H O Me O-n-decyl 2~ 4-CF34-F H O Me O-n-decyl 4-CF3 H H O Me O-n-decyl 4-CF35-Br CO2Me O Me O-n-decyl 4-CF35-Cl CO2Me O Me O-n-decyl Ç-CF35-CF3 CO2Me O Me O-n-decyl ~ 25 4-CF34-F CO2Me Me O-n-decyl 4-CF3 H CO2M.e O Me O-n-decyl 4-CF35-Cl H S Me O-n-decyl 4-C15-Cl H S Me O-n-decyl 4-~r 5-Cl H S Me O-n-decyl 4-CF35-~r H S Me O-n-decyl 4-CF35-F H S Me O-n-decyl 4-C~34-Cl H S Me O-n-decyl 4-CF34-F H S Me O-n-decyl 4-CF3 H H S Me O-n-decyl 4-CF35-Cl CO2Me S Me O-D-decyl 4-CF35-Br CO2Me S Me O-n-decyl 4-CF35-F CO2Me S Me O-n-decyl 4-CF34-Cl CO2Me S Me O-n-decyl 2~Q~65 , Rl R2 B V R8 Rg 4-CF34-F CO2Me S Me O-r-decyl 4-CF3 H CO2Me S Me O-~-aecyl 4-CF35-Br H O Me O-n-dodecyl 4-C15-Br H O Me O-n-dodecyl 4-8r S-Br H O Me O-n-dodecyl 4-OCF35-8r H O Me O-n-dodecyl 4-CF35-Cl H O Me O-n-dodecyl 4-C15-Cl N O Me O-n-dodecyl 4-8r 5-Cl H O Me O-n-dodecyl 4-CF35-CF3 H o Me O-n-dodecyl 4-CF34-F H O Me O-n-dodecyl 4-CF3 H H O Me O-n-dodecyl 4-CF35-8r CO2Me O Me O-n-dodecyl 4-CF35-Cl CO2Me O Me O-n-dodecyl 4-CF35-CF3 CO2Me O Me O-n-dodecyl 4-CF34-F CO2Me O Me O-n-dodecyl 4-CF3 H CO2Me O Me O-n-dodecyl 4-CF35-Cl H S Me O-n-dodecyl 4-C15-Cl H S Me O-n-dodecyl 4-8r 5-Cl H S Me O-n-dodecyl 4-CF35-Br H S Me O-n-dodecyl 4-CF35-F H S Me O-n-dodecyl 4-CF34-Cl H S Me O-n-dodecyl 4-CF34-F H S Me O-n-dodecyl 4-CF3 H H S Me O-n-dodecyl 4-CF35-Cl CO2Me S Me O-n-dodecyl 4-CF35-Br CO2Me S Me O-n-dodecyl 4-CF35-F CO2Me S Me O-n-dodecyl 4-CF34-Cl CO2Me S Me O-n-dodecyl 3~ 4-CF34-F CO2Me S Me O-n-dodecyl ~.:.: .. -: . : : , . . . , ., . ., ; ,: , : .:. .. .: . , . . . . : . : . : . .
2~QQ~6S
Rl R2 B V RB Rg 4-CF3 H C2Me S Me O-n-dodecyl 4-CF35-Br H O Me 0-6ec-Bu 4-C15-Br H O Me O-~ec-Bu 4-Br 5-Br H O Me O-sec-Bu 4-OCF35-Br H O Me O-sec-~u 4-CF35-Cl H O Me 0-6ec-~u 4-C15-Cl H O Me O-~ec-Bu 4-Br 5-Cl H O Me O-cec-Bu 4-CF35-CF3 H o Me O-~ec-Bu 4-CF34-F H O Me O-~ec-Bu 4-CF3 H H O Me 0-6ec-Bu 4-CF35-Br C02Me O Me 0-6ec-Bu 4-CF35-Cl C02Me O Me O-sec-Bu 4-CF35-CF3 C02Me O Me O-~ec-Bu 4-CF34-F C02Me O Me O-~ec-Bu 4-CF3 H C02Me Me O-sec-Bu 4-CF35-Cl H S Me O-~ec-Bu 4-C15-Cl H S Me 0-6ec-Bu ::
4-Br 5-Cl H S Me O-sec-Bu 4-CF35-Br H S Me O-sec-Bu 4-CF35-F X S Me 0-6ec-Bu 4-CF34-Cl H S Me O-sec-Bu 4-CF34-F H S Me O-sec-Bu 4-CF3 H H S Me 0-6ec-Bu 4-CF35-Cl C02Me S Me O-sec-Bu 4-CF35-Br C02Me S ~e O-cec-Bu 4-CF35-F C~2Me S Me O-sec-Bu 4-CF34-Cl C02Me S Me O-sec-Bu 4-CF34-F C02Me S Me O-cec-Bu 4-CF3 H C02Me S Me O-sec-Bu .: ., , , . . . . . . : . : : ,: : : :.
~ . ~ . . . .
2~Q~65 . Rl R2 B V R~ R9 S
4-CF35-Br H O Me O-iPr 4-C15-Br H O Me O-iPr 4-8r 5-Br ~ O Me O-iPr 4-OCF35-Br H O Me O-iPr 4-CF35-Cl H O Me O-iPr 4-C15-Cl H O Me O-iPr 4-8r 5-Cl H O Me O-iPr 4-CF35-CF3 H O Me O-iPr 4-CF34-F H O Me O-iPr 4-CF3 H H O Me O-iPr 4-CF35-Br CO2Me O Me O-iPr 4-CF35-Cl CO2Me O Me O-iPr 4-CF35-CF3 CO2Me O Me O-iPr 4-CF34-F CO2Me O Me O-iPr 4-CF3 ~ CO2Me O Me O-iPr 4-CF35-Cl H S Me O-iPr 4-C15-Cl H S Me O-iPr 4-Br 5-Cl H S Me O-iPr 4-CF35-Br H S Me O-iPr 4-CF35-F H S Me O-iPr 4-CF34-Cl H S Me O-iPr 4-CF34-F H S Me O-iPr q-CF3 H H S Me O-iPr 4-CF35-Cl CO2Me S Me O-~Pr 4-CF35-Br CO2Me S Me O-iPr 4-CF35-F CO2Me S Me O-iPr 4-CF34-Cl CO2Me S Me 9-iPr 4-CF34-F CO2Me S Me O-iPr 4-CF3 ~ CO2Me S Me O-iPr . . . , : , .. : ... , ~, : - .. . .
2~?~Q~65 1 R2 B V R8 Rg 4-CF35-Br H , O Me OCH2CH2Et 4-C15-~r H O Me OCH2CH2OEt 4-Br S-Br ~ O Me OCH2CH2OEt 4-OCF35-Br H O Me OCH2CH2OEt 4-CF35-Cl H O Me OCH2CH2OEt 4-C15-Cl H O Me OCH2CH2OEt 4-Br 5-Cl H O Me OCH2CH2OEt 4-CF3 s-CF3 H o Me OCH2CHzOEt g-CF34-F H O Me OCH2CH2OEt 4-CF3 H H O Me OCH2CB2OEt 4-CF35-Br CO2Me O Me OCH2CH2OEt 4-CF35-Cl CO2Me O Me OCH2CH2OEt 4-CF35-CF3 CO2Me O Me OCH2CH2OEt 4-CF34-F CO2Me Me OCH2CH2OEt 9-CF3 H CO2Me Me OCH2CH2Et 4-CF35-Cl H S Me OCH2CH2OEt 4-C15-Cl H S Me OCH2CH2OEt 4-Br 5-Cl H S Me OCH2CH2OEt 4-CF35-Br H S Me OCH2CH2OEt 4-CF35-F H S Me OCH2CH2OEt 4-CF34-Cl H S Me OCH2CH2OSt 4-CF34-F H S Me OCH2CH2OEt 4-CF3 H H S Me OCH2CH2OEt 4-CF35-Cl CO2Me S Me OCH2CH2OEt 4-CF35-Br CO2Me S Me OCH2CH2OEt 4-CF35-F CO2Me S Me OCH2CH2OEt 4-CF34-Cl CO2Me S Me OCH2CH2OEt 4-CF34-F CO2Me S Me OCH2CH2OEt 4-CF3 H CO2Me S Me OCH2CH2OEt ''''''"' .
- . . . . . : , . . . :.
Z~C~Q~6~;
1 R2 B V Rg Rg 4-CF35 Br H O Me OCH2CC13 4-C15-Br H O Me OCH2CC13 4-Br 5-Br H O Me OCH2CC13 4-OCF35-8r H O Me OCH2CC13 4-CF35-Cl H O Me OCH2CC13 4-C15-Cl H O Me OCH2CC13 4-Br 5-Cl H O Me OCH2CC13 4-CF3 s-CF3 H o Me OCH2CC13 4-CF34-F H O Me OCH2CC13 4-CF3 H H O Me oCH2CC13 4-CF35-Br CO2Me O Me OCH2CC13 4-CF35-Cl CO2Me O Me OCH2CC13 4-CF35-CF3 CO2Me o Me OCH2CC13 4 CF34 F CO2Me O Me OCH2CC13 4-CF3 H CO2Me Me OCH2CC13 4-CF35-CI H S Me OCH2CC13 4-C15-Cl H S Me OCH2CC13 4-Br 5-Cl H S Me OCH2CC13 4-CF35-Br H S Me OCH2CC13 4-CF35-F H S Me OCH2CC13 4-CF34-Cl H S Me OCH2CC13 4-CF34-F H S Me OCH2CC13 4-CF3 H H S Me OCH2CC13 4-CF35-Cl C~2Me S Me OCH2CC13 4-CF35-i3r CO2Me S Me OCH2CC13 4-CF35-F CO2Me S Me OCH2CC13 4-CF34-Cl CO2Me S Me OCH2CC13 ~-CF34-F CO2Me S Me OCH2CC13 4-CF3 H CO2Me S Me OCH2CC13 2~Q~6~;
Rl R2 ~ V R8 Rg _ 4-CF35-Br B O Me OCH2CF3 4-Cl S-Br H O Me OCHzCF3 4-Br 5-Br N O Me GCH2CF3 4-OCF35-Br H O Me OCH2CF3 4-CF35-Cl H O Me OCH2CF3 4-C15-Cl H O Me OCH2CF3 4-Br 5-Cl H o Me OCH2CF3 4-CF35-CF3 H O Me OCH2CF3 4-CF34-F H O Me OCH2CF3 4-CF3 H H O Me OCH2CF3 4-CF35-Br CO2Me O Me OCH2CF3 4-CF35-Cl CO2Me O Me OCH2CF3 4-CF35-CF3 CO2Me O Me OCH2CF3 4-CF34-F CO2Me Me OCH2CF3 4-CF3 H CO2Me Me OCH2CF3 4-CF35-Cl H S Me OCH2CF3 4-C15-Cl H S Me OCH2CF3 4-Br 5-Cl H S Me OCH2CF3 4-CF35-Br H S Me OCH2CF3 4-CF35-F H S Me OCH2CF3 4-CF34-Cl H S Me OCH2CF3 4-CF34-F H S Me OCH2CF3 4-CF3 H H S Me OCH2CF3 4-CF35-Cl CO2Me S Me OCH2CF3 4-CF35-Br CO2Me S Me OCH2CF3 4-CF35-F CO2Me S Me OCH2CF3 4-CF34-Cl CO2Me S Me OCH2CF3 4-CF34-F C02Me S Me OCH2CF3 4-CF3 H C02Me S Me OCH2CF3 . , .......... . , , . . ~ . ...... . . . . . .
.. . ~ . . , , . . , , .. - , .... . .
- . . ~ . . . .
2~?QQ~6~
Rl R2 ~ V R8 R9 4-CF35-9r H O Me CH2c2Et 4-C15-Br H O Me OCH2CO2Et 4-8r 5-Br H o Me CH2c2Et 4-OCF35-8r H O Me OCH2CO2Et 4-CF35-Cl H O Me OCH2C02Et 4-Cl S-Cl H O Me OCH2C02Et 4-Br 5-Cl H O Me OCHzCO2Et q-CF35-CF3 H o Me OCH2C02Et 4 CF34 F H O Me CH2c2Et 4-CF3 H H O Mç OCH2CO2Et 4-CF35-~r CO2Me O Me OCH2C02Et 4-CF35-Cl CO2Me O Me OCH2C02Et 4-CF35-CF3 CO2Me O Me OCH~C02Et 4-CF34-F CO2Me O Me OCH2C02Et 4-CF3 H CO2Me Me CH2c2Et 4-CF35-Cl H S Me OCH2CO2Et 4-CI 5-Cl H S Me OCH2C02Et 4-Br 5-Cl H S Me OCH2CO2Et 4-CF35-8r H S Me OCB2C02Et 4-CF35-F H S Me OCH2CO2Et 4-CF34-Cl H S Me OCH2C02Et 4-CF34-F H S Me OCH2C02Et 4-CF3 H H S Me OCH2C02Et 4-CF35-Cl CO2Me S Me OCB2C02Et 4-CF35-8r CO2Me S Me OCH2C02Et 4-CF35-F CO2Me S Me OCH2C02Et 4-CF34-Cl CO2Me S Me OCB2C02Et 4-CF34-F CO2Me S Me OCN2C02Et 4-CF3 H CO2Me S Me OCH2C02St '~ .' ' .... .... .. . . .... . . .
2C~Q~6~
1 R2 ~3 V R8 Rg 4-CF3 5-Br H O Me F
4-C1 5-Br H O Me F
4-Br S-i3r H O Me F
4-OCF35-Br H O Me F
4-CF3 5-Cl R O Me F
4-C1 5-Cl H 1~ Me F
4-Br 5-Cl H O Me F
4-CF3 5-CF3 H O Me F
4-CF3 4-F H O Me F
lS 4-CF3 H H Me F
4-CF3 5-Br CO2Me O Me F
4-CF3 5-Cl C02Me O Me F
4-CF3 S-CF3 C02Me O Me F
4-CF34-F CO2Me Me F
4-CF3 H CO2Me Me F
4-CF3 5-Cl H S Me F
4-C1 5-Cl H S Me F
4-Br 5-Cl H S Me F
4-CF3 5-Br H S Me F
4-CF3 5-F H S Me F
4-CF3 4-Cl H S Me F
4-CF3 4-F H S Me F
4-CF3 H H S Me F
4-CF35-Cl CO2Me S Me F
3Q 4-CF3 5-Br CO2Me S Me F
4-CF35-F CO2Me S Me F
4-CF34-Cl CO2Me S Me F
4-CF34-F C2Me S Me F
4-CF3 H CO2Me S Me F
~., , - : . - : . -, .. -- - : , :: : :.. :: . , . : ~ . . . : . -Z~ 6~;
96 ~.
Rl R2 B V R8 Rg ,.,~, ~.
4-CF3 5-8r X O Me NMe2 4-Cl S-Br H O Me NMe2 ..
4-Br 5-8r N O Me NMe2 4-OCF35-Br H O Me NMez 4-CF3 5-Cl H O Me NMe2 4-C1 5-Cl H O Me NMe2 4-Br 5-Cl H O Me NMe2 4-cF3 5-cF3 H O Me NMe2 4-CF3 4 F H O Me NMe2 4-CF3 H H O Me NMez 4-CF3 5-Br C02Me O Me NMe2 4-CF3 5-Cl CO2Me O Me ~Me2 :
4-cF3 5-cF3 co2Me O Me NMe2 .:
4-CF34-F CO2Me Me NMe2 4-CF3 H CO2Me Me NMe2 4-CF3 5-Cl H S Me NMe2 4-C1 5-Cl H S Me NMe2 4-Br 5-Cl H S Me NMe2 4-CF3 5-Br H S Me NMe2 ':
4-CF3 5 F H S Me NMe2 4-CF3 4-Cl H S Me NMe2 4-CF3 4 F H S Me NMe2 4-CF3 H H S Me NMe2 4-CF35-Cl t:O2Me S Me NMe2 4_CF35-Br CO2Me S Me NMe2 4-CF35-F CO2Me S Me NMe2 : .
4-CP34-Cl CO2Me S Me NMe2 4-CF34-F C2Me S Me ~Me2 4-CF3 H C2Me S Me NMe2 :
, .. . - . :-:: - ., : .: ; . . ..
.,. ! ~ . . . .
', .~. '''' ' '.', ' ., ' "' ' . ' . ' , ' . ', '''' .. .. ' , ' .
2~t~Qt~iS
Rl R2 B V Pg Rg 4-CF35-Br H O Et O-iPr 4-C15-~r ~ O Et O-iPr 4-~3r S-Br ~ O Et O-iPr 4-OCF35-Br H O Et O-iPr 4-CF35-Cl H O Et O-iPr 4-C15-Cl H O Et O-iPr 4-Br 5-Cl H O Et O-iPr 4-CF35-CF3 H o Et O-iPr 4-CF34-F H O Et O-iPr 4-CF3 H H O Et O iPr 4-CF35-Br CO2Me O Et O-iPr 4-CF35-Cl CO2Me O Et O-iPr 4-CF35-CF3 CO2Me O Et O-iPr 4 CF34 F CO2Me Et O-iPr 4-CF3 H CO2Me O Et O-iPr 4-CF35-Cl H S Et O-iPr 4-C15-Cl H S Et O-iPr 4-Br 5-Cl H S Et O-iPr 4-CF35-Br H S Et O-iPr 4-CF3 S-F H S Et O-iPr 4-CF34-Cl H S Et O-iPr 4-CF34-F H S Et O-iPr 4-CF3 H H S Et O-iPr 4-CF35-Cl CO2Me S Et O-iPr 4-CF35-Br CO2Me S Et O-iPr 4-CF35-F C02Me S Et O-iPr 4-CF34-Cl CO2Me S Et O-iPr 4-CF34-F CO2Me S Et O-iPr 4-CF3 H CO2Me S Et O-iPr .' ' ., . ' : ', " ~ ' , ' ' ' .: ' ' ' , ' ' ' ' Z~Q~65 Rl R2 B V R8 Rg 4-CF35-Br H O iPr OEt 4-C15-Br H O iPr OEt 4-Br 5-Br H O iPr OEt 4-OCF35-Br H O iPr OEt 4-CF35-Cl H O iPr OEt 4-C15-Cl H O iPr OEt 4-Br 5-CI H O iPr OEt 9-CF35-CF3 H O iPr OEt 4-CF34-F H O iPr OEt 4-CF3 H H O iPr OEt 4-CF35-Br CO2Me O iPr OEt 4-CF35-Cl CO2Me O iPr OEt 4-CF35-CF3 CO2Me O iPr OEt 4-CF34-F CO2Me O iPr OSt 4-CF3 H CO2Me iPr OEt 4-CF35-Cl H S iPr OEt 4-C15-Cl H S iPr OEt 4-Br 5-Cl H S iPr OEt 4-CF35-Br H S iPr OEt 4-CF35-F H S iPr OEt 4-CF34-CI H S iPr OEt 4-CF34-F H S iPr OEt 4-CF3 H H S iPr OEt 4-CF35-C~ C~2Me S iPr OEt 4-CF35-Br CO2Me S iPr OEt 4-CF35-F CO2Me S iPr OEt 4-CF34-C~ CO2Me S iPr OEt 4-CF34-F C2Me S iPr OEt 4-CF3 H CO2Me S iPr OEt - : . . . :
- . , ~3Q~6S
4-CF35-9r H O iPr O-nBu 4-C15-Br H O iPr O-nBu 4-Br 5-Br H O .iPr O-nBu 4-OCF35-Br H O iPr O-nBu 4-CF35-Cl H O iPr O-nBu 4-C15-Cl H O iPr O-DBu ' 4-Br 5-Cl H O iPr O-nBu 4-CF35-CF3 H o iPr O-nBu 4-CF34-F H O iPr O-~Bu lS 4-CF3 H H iPr O-nBu 4-CF35-Br C02Me O iPr O-nBu 4-CF35-Cl C02Me O iPr O-nBu 4-CF35-CF3 C02Me O iPr O-nBu 4-CF34-F C02Me O iPr O-nBu 4-CF3 H C02Me iPr O-nBu 4-CF35-Cl H S iPr O-nBu 4-C15-Cl H S iPr O-nBu 4-Br 5-Cl H S iPr O-nBu 4-CF35-Br H S iPr O-nBu 4-CF35-F H S iPr O-nBu ;
4-CF34-C18 S iPr O-nBu 4-CF34-F H S iPr O-nBu 4-CF3 H H S iPr O-nBu 4-CF35-Cl C02Me S iPr O-nBu 4-CF35-Br C02Me S iPr O-nBu 4-CF35-F C02Me S iPr O-nBu 4-CF34-Cl C02Me S iPr O-nBu 4-CF34-F C02Me S iPr O-nBu 4-CF3 H C02Me S iPr O-DBu , '~
. . .. , -:: .: : ~ . , :. , , : :
.. ., : .. : .. - . . . : " . ~::
2~ Q~6S
100 :, Rl R2 B V R8 Rg , 4-CF3 5-Br H O iPr OCH2cF3 4-C1 5-Br H O iPr OCH2CO2Me 4-Br 5-Br H O iPr NMe2 4-OCF3 5-Br H O iPr NEt2 4-CF3 5-Cl H O iPr piperidino 4-C1 5-Cl H O iPr Et 4-Br 5-Cl H O iPr 4-Br-Ph 4-CF3 5-CF3 H O CH2Ph OEt 4-CF3 4-F H O CH2Ph O-n-octyl 4-CF3 H H O CH2Ph OCH2CO2Et 4-CF3 5-Br CO2Me CH2Ph F
4-CF3 5-Cl CO2Me CH2Ph NEt2 4-CF3 5-CF3 CO2Me O CH2Ph morpholino .;
4-CF3 4-F CO2Me CH2Ph 4-Cl-Ph 4-CF3 H CO2Me O CH2Ph Et . .
4-CF3 5-Cl H S CH2Ph Ph . . . - .. - . . : ,: . . , , . :
- . : . .: . . - :
- . : . - . .. :
. , - - - . ; . - :. . - : : : -. . . : , , : , . . .
-2~ 65 ~ble 9 Rl .:
~ N O
O S-N-S-R~
R~O
Rl R2 B V R8 Rg 4-CF3 5-Br H O Me NMe2 4-C1 5-Br H O Me NMe2 -4-Br 5-Br H O Me NMe2 4-OCF3 5-Br H O Me NMe2 4-CF3 5-Cl H O Me NMe2 4-C1 5-Cl H O Me NMe2 3~ 4-Br 5-Cl H O Me NMe2 :-4-CF3 s-CF3 H o Me NMe2 4-CF3 4 F H O Me NMe2 :
4-CF3 H H O Me NMe2 q-CF3 s-Br CO2Me O Me NMe2 ~:
4-CF3 5-Cl CO2~e O Me NMe2 .
',:
!~
..
.' , , .
'; ' ; ' ' ~ . ' ' ' ' ' i ~ . . ! .
2~ 6s Rl R2 B V R8 Rg 4-CF35-CF3 CO2Me O Me NMe2 4-CF34-F C02Me Me NMe2 4-CF3 H CO2Me O Me NMe2 4-CF35-Cl H S Me NMe2 9-C15-Cl H S Me NMe2 4-Br 5-Cl H S Me NMe2 4-CF35-Br H S Me NMe2 4 CF35 F H S Me NMe2 4-CF34-Cl H S Me NMe2 4-CF34-F H S Me NMe2 4-CF3 H H S Me NMe2 4-CF35-Cl CO2Me S Me NMe2 4-CF35-Br CO2Me S Me NMe2 4-CF35-F CO2Me S Me NMe2 4-C}34-Cl CO2Me S Me NMe2 4-CF34-F CO2Me S Me NMe2 4-CF3 H CO2Me S Me NMe2 4-CF35-Br H O Me NEt2 4-C15-Br H O Me NEt2 4-Br 5-Br H O Me NEt2 4-OCF35-Br ~ O Me NEt2 4-CF35-Cl H O Me NEt2 4-C15-Cl H O Me NEt2 4-Br 5-Cl H O Me NEt2 4-CF35-CF3 H O Me NEt2 4-CF34-~ H O Me NEt2 4-CF3 H H O Me NEt2 4-CF35-Br CO2Me O Me NEt2 4-CF35-Cl CO2Me O Me NEt2 4-CF35-CF3 CO2Me O Me NEt2 4-CF34-F CO2Me O Me NEt2 4-CF3 H CO2Me Me NEt2 , ;'.' ` ''~ ' , ~', " " ' . ', ', . . ' ' .
, ", 2~7~Q~6S
R2 B V R8 Rg 4-CF35-Cl H S Me NEt2 4-C15-Cl H S Me NEt2 4-Br 5-Cl H S Me NEt2 4-CF35-~r H S Me NEt2 10. 4-CF35-F H S Me NEt2 4-CF34-C18 S Me NEt2 4-CF34-F H S Me NEt2 4-CF3 H ~ S Me NEt2 4-CF35-Cl CO2Me S Me NEt2 lS 4-CF35-Br CO2Me S Me NEt2 4-CF35-F CO2Me S Me NEt2 4-CF34-Cl CO2Me S Me NEt2 4-CF34-F CO2Me S Me NEt2 4-CF3 H CO2Me S Me NEt2 4-CF35-Br H O Me piperidino 9-C15-Br H O Me 6ec-Bu 4-Br 5-9r H O Me D-he~yl 4-OCF35-Br H O Me Ph .
4-CF35-Cl H O Me 4-Cl-Ph :
4-C15-Cl H O Me 4-Me-Ph :
4-Br 5-Cl H O Me n-Bu 4-CF35-CF3 H O Et NMe2 4-CF34-F H O Et NEt2 4-CF3 H H O Et morpboli~o :
4 CF35-S3r CO2Me O Et ~Pr 4-CF35-Cl CO2Me O Et n-Bu 4-CF35-CF3 CO2Me O Et Ph 4-CF34-F CO2~e O Et 4-M~O-Ph !;``
q-CF3 H CO2Me Me NMe2 4-CF35-Cl H S Me NEt2 4-C15-Cl H S Me morpholiDo 4-9r 5-Cl H S Me iPr ,, .. : . : ., . , ... . ~:. : .. .. .
Rl R2 B V R8 R9 -.4-CF35-Br H S Me n-B~.
4-CF35-F H S Me Ph 4-CF34-Cl X. S Me 4-MeO-Ph 4-CF34-F B S Et piperidioo 4-CF3 H H S Et 6ec-Bu 4-CF35-Cl CO2Me S Et n-hesyl 4-CF35-Br C02Me S Et Ph 4-CF35-F CO2Me S Et 4-Cl-Ph 4-CF34-Cl CO2Me S Et 4-Me-Ph 4-CF34-F COzMe S Et n-Bu 4-CF3 H CO2Me S Et 2,6-~i-Me-morpholino 4-CF35-Br H O iPr NMç2 4-Cl S-Br H O iPr NMe2 4-8r 5-Br H O iPr NMe2 4-OCF35-Br H O iPr NMe2 4-CF35-Cl H O iPr ~Me2 4-Cl S-Cl H O iPr NMe2 4-Br 5-Cl H O iPr NMe2 4-CF35-CF3 H O iPr NMe2 4-CF34-F H O iPr NMe2 4-CF3 H H O lPr NMe2 :~
4-CF35-Br CO2Me O iPr 'NMe2 4-CF35-Cl CO2Me O iPr NMe2 4-CF35-CF3 CO2Me O iPr NMe2 4-CF34-F C02Me iPr NMe2 4-CF3 H C02Me lPr NMe2 , 4-CF35-Cl H S iPr NMe2 :
4-C15-Cl H S iPr NMe2 4-Br 5-Cl H S iPr N~.e2 4-CF35-Br H S iPr NMe2 4-CF35-F H S iPr NMe2 :.
, -, :
2C~Q~L65 105 ..
Rl R2 B V R8 Rg __ S .
4-CF3 4-Cl H S iPr NMe2 4-CF3 4-~ H S iPr NMe2 4-CF3 H H S iPr NMe2 4-CF3 5-Cl C02Me S iPr NMe2 4-CF3 5-Br CO2Me S iPr NMe2 4-CF3 S-F CO2Me S iPr NMe2 4-CF3 4-Cl C02Me S iPr NMe2 4-CF3 4-F CO2Me S iPr NMe2 4-CF3 H CO2Me S iPr NMe2 :
21~ 65 Table 10 lC
~ N Y
O S-N-P-Y Rlo R~Y Rll Rl R2 B V R8 Y . Y Rlo Y Rll 4-CF3 5-Br H O tBu S OEt OEt 4-.C1 5-Br H O tBu S OEt OEt 4-Br 5-Br H O tBu S OEt OEt 4-OCF3 5-Br H O tBu S OEt OEt 4-CF3 5-Cl H O tBu S OEt OEt 4-C1 5-Cl H O tBu S OEt OEt 4-Br 5-Cl H O tBu S OEt OEt 4-CF3 5-CF3 H O tBu S OEt OEt 4-CF3 4-F H O tBu S OEt OEt 4-CF3 H H O tBu S OEt OEt 4-CF3 5-Fr CO2Me O tBu S OEt OEt 4-CF3 5-Cl CO2Me O tBu S OEt OEt 4-CF3 S-CF3 C02Me O tBu S OEt OEt 3~
- ~ ~ : , ::, . -, . :
- - . : . . ... .
Q~65 Rl R2 B V R8 Y y Rlo Y R
.
4 CF34 F CO2Me O tBu S OSt OEt 4-CF3 H CO2Me O tBu S OEt OEt 4-CF35-Cl H S t8u S OEt OEt 4-C15-Cl H S t8u S OEt OEt 4-Br 5-Cl H S tBu S OEt OEt 4-CF35-Br H S tBu S OEt OEt 4-CF35-~ R S tBu S OEt OEt 4-CF34-Cl H S tBu S OEt OEt 4-CF34-F H S tBu S O~t OEt 4-CF3 H H S tBu S OEt OEt 4-CF35-Cl CO2Me S tBu S OEt OEt 4-CF35-Br CO2Me S tBu S OEt OEt 4-CF35-F CO2Me S tBu S OEt OEt 4-CF34-Cl CO2Me S tBu S OEt OEt 4-C~34-~ CO2Me S tBu S OEt OEt 4-CF3 H CO2Me S tBu S OEt OEt 4-CF35-Br N O tBu S -OCH2C(Me)2CH2O-4-C15-Br H O tBu S -OCH2C(Me)2CH2O-4-Br 5-Br H O tBu S -OCH2C(Me)2CB2O-4-OCF35-Br H O tBu S -OCH2C(Me)2CH2O-4-CF35-CI H O tBu S -OCH2C(Me)2CH2O_ 4-C15-Cl H O tBu S -OCH2C(Me)2CH2O-4-Br S-Cl H O tBu S -OCH2C(Me)2CH2O-4-CF35-CF3 H O tBu S -OCH2C(Me)2CH2O-~n 4-CF34-F H O tBu S -OCH2C(Me)2CH2O-4-CF3 H H O tBu S -OCH2C(Me)2CB2O-4-CF35-i3r CO2Me O tBu S -OCH2C(Me)2CH2O-4 CF35-Cl CO2Me O tBu S -OCH2C(Me~2CH2O-4-CF35-CF3 CO2Me O tBu S -OCH2C(Me)2CN2O-4-CF34-F CO2Me O tBu S -OCH2C(Me)2CH2O-4-CF3 H CO2Me O tBu S -OCH2C(Me)2CH2O-4-CF3 5-Cl H S tBu 5 -OCH2C(Me)2CH2O-'`'"
. . .
':~., - . . . . . . . . .: .. . ~ :. .; .: :,. .: .. .
2~ 65 Rl R2 El V R8 Y ' Y Rlo Y Rll 4-C15-Cl H S tBu S -OCH2C(Me)2CH2O_ q-Br 5-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF35-Br H S tBu S -OCHzC(Me)2CH2O-4-CF35-F N S tBu S OCH2C(Me)2CH2O-4-CF34-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF34-F H S tBu S -OCH2C(Me)2CB2O- ~.
4-CF3 H H S tBu S -OCH2C(Me)2CH2O-4-CF3 ~-Cl CO~e S tBu S -OCH2C(Me)2CH20-4-CF35-~ CO2Me S tBu S -OC~2C~Me)2CH2O_ 4-CF35-F C02Me S tBu S -OCH2C(Me)2CH2o-4-CF34-Cl C02Me S tBu S -OCH2C(Me)2CH2O-4-CF34-~ CO2Me S tBu S -OCH2C(~e)2CH2O-4-CF3 H C02Me S tBu S -OCH2C(Me)2CH2O-4-CF35-Br H O tBu S OCH2CH2CH20-4-Cl S-Br H O tBu S -OCH2CH2CH20- .
4-Br 5-Br H O tBu S -OCH2CH2CH20-4-OCF35-Br H O tBu S -CH2cH2cH2- l~
4-CF35-Cl H O tBu S -OCH2CH2CH20- ~. -4-Cl S-Cl H O tBu S -CH2cH2cH2-4-Br 5-Cl H O tBu S -OCH2CH2CH2O-4-CF35-CF3 H o tBu S -OCH2CH2CH2O-4-CF34-F H O tBu S -OCH2CH2CH2O-4-CF3 H H O tBu S -OCH2CH2CH2O- ~:
4-CF35-Br CO2Me O tBu S -OCH2CH2CH2O-4-CF35-Cl C02Me O tBu S -OCH2CH2CH20- : :
4-CF35-CF3 CO2Me O tBu S -CH2cH2cH2-4-CF3 ~-F CO2Me O tBu S -OCH2CH2CH2O-q-CF3 H C02Me tBu S -CH2cH2cH2-4-CF35-Cl H S tBu S OCH2CH2CH20-4-C15-Cl H S tBu S -OCH2CH2CH2O-4-Br 5-Cl H S tBu S -C~2cH2cH2- ;
,, . ~ . , . . , . .... ~ .. ., . , , . . . .. - : . ..
Rl R2 B V R8 Y Y al0 Y Rll 4-CF35-Br H . S tBu S -OCH2CH2CH2O
4-CF35-F H S tBu S -OCH2CH2CH2O-4-CF34-Cl U S tBu S -OCH2CH2C-H20 4-CF34-F N S tBu S -CH2cH2cH2- !`
4-CF3 H H S tBu S -OCH2CH2CH2O-4-CF3 5-Cl CO2Me S tBu S -QCH2CH2CH2O-4-CF3 5-Br CO2Me S t8u S -OCH2CH2CH2O-4-CF3 5-F CO2Me S tBu S -OCH2CH2CH2O-4-CF3 4-Cl CO2Me S tBu S -OCH2CH2cH2O- :
4-CF34-F CO2Me S tBu S -OCH2CH2CH2O-4-CF3 H CO2Me S tBu S -OCH2CH2CH2O-4-CF35-8r H O t8u S OCHzCH2O
4-C15-8r H O tBu S -OCH2C~2O-4-Br 5-Br H O tBu S -OCH2CH2O-2C 4-OCF35-Br H O tBu S -OCH2CH2O-4-CF35-Cl H O tBu S -OCH2CH2O-4-C15-Cl H O tBu S -OCH2~2O-4-Br S-Cl H O tBu S -OCH2CH2O-4-CF35-CF3 H O tBu S -OCH2CH2O-4-CF34-F H O tBu S -OCH2CH2O-4-CF3 H H O tBu S -OCHzCH2O-4-CF35-Br CO2Me O tBu S -OCH2CH2O- .. -4-CF35-Cl CO2Me O tBu S -OCH2CH2O-4-CF35-CF3 CO2Me O tBu S -CH2cH2 . ~`
4-CF34-F CO2Me tBu S -OCH2CH2O-4-CF3 H CO2Me O tBu S -OCH2CH2O- ~
4-CF35-Cl H S tBu S -OCH2CH2O- , -4-Cl S-Cl H S tBu S -CH2cH2- `~ :
4-Br S-Cl H S tFu S -OCH2CH2O-4~CF35-Br H S tBu S -CH2~2-4-CF35-~ H S t8u S -OCH2CH2O- ..
4-CF34-Cl H S tBu S -OCH2CH2O-., :, -. , . .. , , . - . : :. . ~ . ..... : . : - : :::, ,: .
:. . , ,, ,. , ,: .. ,..~, . ;'. '-, '.. ' , . -: : '' ' :': ' '. " ' ;' ., ' ': ~ '. -'." .-'', :. ' . , .'',.,... ,. ':, ,, ' ~Q~6S
R2 B V RB ~ ~ Rlo Y Rll 4 CF34 F ~ S t~u S -OCH2CH20-4-CF3 H B S tBu S OC~2CH20-4-CF35-Cl CO2Me S tBu S -OCH2CH~O-4-CF35-~r CO2Me S tBu S -OCH2CH20-4-CF35-F CO2Me S tBu S -OCH2CB20-4-CF34-CI COzMe S tBu S -OCH2CH20-q-CF34-F CO2Me S tBu S -OCH2CH20-4-CF3 H CO2Me S tBu S -OCH2C~20-4-CF35-Br H O iPr S OEt OEt 4-C15-8r H O iPr S OEt OEt 4-Br S-Br H O $Pr S OEt OEt 4-OCF35-Br H O iPr S OEt OEt 4-CF35-Cl H O iPr S OEt OEt 4-C15-Cl H O iPr S OEt OEt 4-Br 5-Cl H O iPr S OEt OEt 4-CF35-CF3 H o iPr S OEt OEt 4-CF34-F H O iPr S OEt OEt 4-CF3 H B O iPr S OEt OEt 4-CF35-8r CO2Me O iPr S OEt OEt 4-CF35-Cl CO2Me O iPr S OEt OEt 4-CF35-CF3 CO2Me O iPr S OEt OEt 4-CF34-F CO2Me iPr S OEt OEt 4-CF3 H CO2Me iPr S OEt OEt .
4-CF35-Cl H. S iPr S OEt OEt 4-C15-Cl H S iPr S OEt OEt 4-Br S-Cl H S iPr S OEt OEt 4-CF35-~r H S iP~ S OEt OEt 4-CF35-F H S iPr S OEt OEt 4-CF34-Cl H S iPr S OEt OEt 4-CF34-F H S iPr S OEt OEt 4-CF3 H H S iPr S OEt OEt 4-CF35-Cl CO2Me S iPr S OEt OEt : -: . : . . .: ~ .: . : . .
.. .... . . . . .. . . ... : .:
2~ 6~;
Rl R2 B V R8 Y y Rlo Y Rll 4-CF35-Br CO2Me S iPr S OEt OEt 4 CF35 F CO2Me S iPr S OEt OEt 4-CF34-Cl CO2Me S iPr S OEt OEt 4-CF34-F CO2Me S iPr S OEt OEt 4-CF3 N CO2Me S iPr S OEt OEt 4-CF35-Pr H O iPr S -OCH2C(Me)zCH2O-4-C15-Br H O iPr S -OCH2C(Me)2CH2O-9-Br S-Br ~ O iPr S -OCH2C(Me)2CH2O-4-OCF35-Br H O iPr S -OCH2C(Me)2CH20-4-CF35-Cl H O iPr S -OCH2C(Me)2CH2O-4-C15-Cl H O iPr S -OCH2C(Me)2CH2O-4-Br 5-Cl H O iPr S -OCH2C(Me)2CH2O-4-CF35-CF3 H o iPr S -OCB2C(Me)2CH2O_ 4-CF34-F H O iPr S -OCH2C(Me)2CH2O-4-CF3 H H O iPr S-OCH2C(Me)2CH2O-4-CF35-Br CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF35-Cl CO2Me O iPr S OCH2C(Me)2cH2O-4-CF35-CF3 CO2Me OiPr S -OCH2C(Me)2CH2O-4-CF34-F CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF3 H CO2Me iPr S -OCH2C(Me)2CH2O-4-CF35-Cl H S iPr S -OCH2C(Me)2CH2O-4-C15-Cl H - S iPr S -OCH2C(Me)2CH2O-4-Br 5-Cl H S iPr S -OCH2C(Me)2CB2O-4-CF35-Br H S iPr S -OCH2C(Me)2CH2O-4-CF35-F H S iPr S -OCH2C(Me)2CH2O-4-CF34-Cl H S iPr S -OCH2C(Me)2CH2O-4-CF34-F H S iPr S -OCH2C(Me)2CH2O-4-CF3 H H S iPr S -OCH2C(Me)2CH2O-4-CF3 5-Cl CO2Me SiPr S -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me SiPr S OCH2C(Me)2c~2O-4-CF3 5-F CO2Me SiPr S -OCH2C(Me)2CH2O-~,:
~ .
'' ' ' ':
. . ~ . : :, : , .... ,, , . ,. :: . . ,, . .. . . ::
.: ,, , ~ : . , , .:
r~ , ~o~s ~1 R2 B V R8 Y Y ~1~ Y Rll ;
4-CF34-Cl CO2Me S iPr S -OCH2C(Me)2CH20-4 CF34 F CO2Me S iPr S -OCH2C(Me)2CH20-4-CF3 H CO2Me S iPr S _ocH2c(Me)2~H2 4-CF35-~r ~ O Me S OEt OEt 4-C15-8r H O Me S OEt OEt 4-Br 5-Br H O Me S OEt OEt 4-OCF35-Br H O Me S OEt OEt 4-CF35-Cl H O Me S OEt OEt 4-C15-Cl R O Me S OEt OEt 4-iBr 5-Cl H O Me S OEt OEt 4-CF35-CF3 H O Me S OEt OEt 4-CF34-F H O Me S O~t OEt 4-CF3 H H O Me S OEt OEt 4-CF35-Br C02Me O Me S OEt OEt 4-CF35-Cl CO2Me O Me S OEt OEt 4-CF35-CF3 CO2Me O Me S OEt OEt 4-CF34-F C02Me O Me S OEt OEt 4-CF3 H CO2Me Me S OEt OEt 4-CF35-Cl H S Me S OEt OEt 4-C15-Cl H S Me S OEt OEt 4-Br 5-Cl H S Me S OEt OEt 4-CF35-Br H S Me S OEt OEt 4-CF35-F H S Me S OEt OEt 4-CF34-Cl H S Me S OEt OEt 4-CF34-F H S Me S OEt OEt 4-CF3 H H S Me S OEt OEt 4-CF35-Cl CO2Me S Me S OEt OEt 4-CF35-Br CO2Me S Me S OEt OEt .:
4-CF35-F CO2Me S Me S OEt OEt 4-CF34-Cl C02Me S Me S OEt OEt 4-CF34-~ CO2Me S Me -S OEt OEt 4-CF3 H CO2Me S Me S OEt OEt ~ ' .. - . ~ : : : ................. . ~ - : , . .:........ . ..
, .: . . - , :: . - . :
Z~Q~65 ~1 R2 B V R8 Y y Rlo Y ~11 _ _ 4-CF35-9r ~ O tBu O OEt OEt 4-C15-8r H O tBu O OEt OEt 4-8r 5-Br N O tBu O OEt OEt 4-OCF35-Br H O tBu O OEt OEt 4-CF35-Cl H O tBu O OEt OEt 4-C15-Cl H O tBu O OEt OEt 4-Br 5-Cl H O tBu O OEt OEt 4-CF3 s-CF3 ~ o ti3u O OEt OEt 4-CF34-F H O tBu O OSt OEt 4-CF3 H H O tBu O OEt OEt 4-CF35-Br CO2Me O tBu O OEt OEt 4-CF35-Cl CO2Me O tBu O OEt OEt 4-CF35-CF3 CO2Me O tBu O OEt OEt 4-CF34-F CO2Me O tBu O OEt OEt 4-CF3 N CO2Me O tBu O OEt OEt 4-CF35-Cl H S tBu O OEt OEt 4-C15-Cl H S tBu O OEt OEt 4-Br S-Cl H S tBu O OEt OEt 4-CF35-Br N S tBu O OEt OEt 4-CF35-F H S tBu O OEt OEt 4-CF34-Cl H S tBu O OEt OEt 4-CF34-F H S tBu O OSt OEt 9-CF3 H H S tBu O OEt OEt 4-CF35-Cl CO2Me S tBu O OEt OEt 4-CF3 S-BI CO2Me S tBu O OSt OEt 4-CF35-F CO2Me S tBu O OEt OEt 4-CF34-Cl CO2Me S tBu O OEt OEt 4-CF34-F CO2Me S tBu O OEt OEt 4-CF3 H CO2Me S tBu O OEt OEt ' 2C~
Rl R2 ~ V R8 Y ' Y Rlo Y Rll 4-CF35-Br H O tBu O -OCH2CtMe~2CH2O-4-C15-Br ~ O t8u O -OCH2C(Me)2CH2O-4-Br 5-Br H O tBu O -OCH2C(Me)2cH2O-4-OCF35-8r H O tBu O -OCH2C(Me)2CH2O-4-CF35-Cl H O tBu O -OCH2C(Me)2CH2O-4-C15-Cl H O tBu O -OCH2C(Me)2CH2O-4-9r S-C~ H O tBu O -OCH2C(Me)2CH2O-9-CF35-CF3 H O t8u O -OCH2C(Me)2CH2O-4 CF34 F H O tBu O -OCH2C(Me)2CH2o_ 4-CF3 H H O tBu O -OCH2C(Me)2CH2O-4-CF35-Br CO2Me O tBu O -OCH2C(Me)zCH2O-4-CF35-Cl CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF35-CF3 CO2Me O t8u O -OCH2C(Me)2CH2O-4 CF34 ~ CO2Me O tBu o -OCH2C(Me)2CH2O-4-CF3 H CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF35-Cl H S tBu O -OCH2C(Me)2CH2O-q-C15-Cl H S tBu O -OCH2C(Me)2CH2O-4-Br 5-Cl H S tBu O -OCH2C(Me)2CH2O-4-CF35-Br H S tBu O -OCH2C(Me)2CH2O-2S 4-CF35-F H S tBu O -OCH2C(Me)2CH2O-4-CF34-Cl H S tBu O -OCH2C(Me)2CH2O-4-CF34-F ~ S tBu O -OCH2C(Me)2CH2O-4-CF3 H H S tBu o -OCH2C(Me)2CH2O-4-CF35-Cl CO2Me S tBu O -OCH2C(Me)2CH2O-3~ 4-CF35-Br CO2Me S t8u O -OCH2C(Me)2CH2O-4-CF35-F CO2Me S tBu O -OCH2C(Me)2CH2O-4-CF34-Cl CO2~e 5 tBu O OCH2C(Me)2C~20 4-CF34-F CO2Me S tBu O -OCH2C(Me)2CH2O-4-CF3 H CO2Me S tBu O -OCH2C(Me)2~2 .
21~B~65 ~ble 11 . -5 . j~
4 `~
N-N ~
~ N ,y, .
O S-N-P-Y Rl, 1 1 :
R~Rlo :
. :
Rl R2 B V R8 Y Rlo Y Rll .
. . .
4-CF3 5-Br H O iPr O Et OEt 4-C1 5-Br H O iPr O Et OEt ,,~:-4-Br 5-Br H O iPr O Et OEt - 4-OCF3 5-Br H O iPr O Et OEt 4-CF3 5-Cl H O iPr O Et OEt ..
4-C1 5-Cl H O iPr O Et OEt : -4-Br 5-Cl H O iPr O Et OEt 4-CF3 5-CF3 H iPr O Et OEt 4-CF3 4-F H O iPr O Et OEt ~:;
4-CF3 H H O iPr O Et OEt -:
4-CF3 5-Br CO2Me iPr O Et OEt 4-~F3 5-Cl CO2Me iPr O Et OEt .
': -,:
,, . ,: . : : .
6~
Rl R2 B V ~8 Y' Rlo Y R
4-CF35-CF3 CO2Me O iPr O Et OEt 4-CF34 F CO2Me iPr O Et OEt 4-CF3 H CO2Me iPr O Et OEt 4-CF35-Cl H S iPr O Et OEt 4-C15-Cl ~ S iPr O Et OEt 4-Br 5-Cl H S iPr O Et OEt 4-CF35-8r H S iPr O Et OEt 4-CF35-F H S iPr O Et OEt 4-CF34-Cl H S iPr O Et OE t 4-CF34-F H S iPr O Et OEt 4-CF3 H H S iPr O Et OEt 4-CF35-Cl CO2Me S iPr O Et OEt 4-CF35-Br CO2Me S iPr O Et OEt 4 CF35 F CO2Me S iPr O Et OEt 4-CF34-Cl CO2Me S iPr O Et OEt 4-CF34-F CO2Me S iPr O Et OEt 4-CF3 H CO2Me S iPr O Et OEt 4-CF35-Br H O iPr O Et O-iPr 4-C15-Br H O iPr O Et O-iPr 4-Br 5-Br H O iPr O Et O-iPr 4-OCF35-Br H O iPr O Et O-iPr 4-CF35-Cl H O iPr O Et O-iPr 4-C15-Cl H O iPr O Et O-iPr 4-Br 5-Cl H O iPr O Et O-iPr 4-CF35-CF3 H iPr O Et O-iPr 4-CF34-F H O iPr O Et O-iPr 4-CF3 H N O iPr O Et O-iPr 4-CF35-Br CO2Me iPr O Et O-iPr 4-CF35-Cl CO2Me O iPr O Et O-iPr 4-CF35-CF3 CO2Me o iPr O Et O-iPr 4-CF34-F CO2Me iPr O Et O-iPr 4-CF3 H CO2Me iPr O Et O-iPr ~ . .
, , . . . ... , ,, ~, . , ,,, .. , . . .. . , . ; .... -- . - .
t6~
Rl R2 B V R8 Y Rlo Y Rll_ .
4-CF35-Cl H S iPr O Et O-iPr 4-C15-Cl H S iPr O Et O-îPr 4-Br 5-Cl H S iPr O Et O-iPr 4-CF35-Rr H S iPr O Et O-iPr 4-CF35-F H S iPr O Et O-iPr 4-CF34-CI H S iPr O Et O-iPr 4-CF34-F H S iPr O Et O-iPr ., 4-CF3 H H S iPr O Et O-iPr 4-CF35-Cl CO2Me S iPr O Et O-iPr 4-C~35-~r CO2~e S iPr O Et O-iPr 4-CF35-F CO2Me S iPr O Et O-iPr 4-CF34-Cl CO2Me S iPr O Et O-iPr 4-CF34-F CO2Me S iPr O Et O-iPr 4-CF3 H CO2Me S iPr O Et O-iPr , .
4-CF35-Br H O iPr O Et OPh 4-C15-Br H O iPr O Et OPh 4-Pr 5-~r H O iPr O Et OPh 4-OCF35-Pr H O iPr O Et OPh 4-CF35-Cl H O iPr O Et OPh 4-C15-Cl H O iPr O Et OPh 4-~r 5-Cl H O iPr O Et OPh : .
q-C~35-CF3 H o iPr O Et OPh 4-CF34-F H O iPr O Et OPh 4-CF3 H H O iPr O Et OPh 4-CF35-Br CO2Me O iPr O Et OPh 4-CF35-Cl CO2Me iPr O Et OPh 4-CF35-CF3 CO2Me O iPr O Et OPh 4-CF34-F CO2Me O iPr O Et OPh ;.
4-C~3 H CO2Me O iPr O Et OPh 4-CF35-Cl H S iPr O Et OPh 4-C15-Cl H S iPr O Et OPh , .~ . :- .: ,: : .:
2~Q~6S
llB
Rl R2 B V R8 Y' Rl~ Y R
9-Br 5-CI H S iPr O Et OPh 4-CF35-Br H S iPr O Et OPh 4-CF35-F H S iPr O Et OPh 4-CF34-Cl H S iPr O E~ OPh 4-CF34-F H S iPr O Et OPh 4-CF3 H H S iPr O Et OPh 4-CF35-Cl C02Me S iPr O Et OPh 4-CF35-9r CO2Me S iPr O Et OPh 4-C~35-F CO2Me S iPr O Et OPh 4-CF34-Cl C02~e S iPr O Et OPh 4-CF34-F CO2Me S iPr O Et OPh 4-CF3 H CO2Me S iPr O Et OPh 4-CF35-Br H O iPr O Ph OEt 4-C15-~r H O iPr O Ph OEt 4-Br 5-Br H O iPr O Ph OEt 4-OCF35-Br N O iPr O Ph OEt 4-CF35-Cl H O iPr O Ph OEt 4-C15-Cl H O iPr O Ph OEt 4-Br 5-Cl H O iPr O Ph OEt 4-CF35-CF3 H o iPr O Ph OEt 4-CF34-F H O iPr O Ph OEt 4-CF3 N H O iPr O Ph OEt 4-CF35-Br CO2Me O iPr o Ph OEt 4-CF35-Cl CO2Me O iPr O Ph OEt 4-CF35-CF3 CO2Me O iPr O Ph OEt 4-CF34-F CO2Me iPr O Ph OEt 4-CF3 H . CO2Me O iPr O Ph OEt 4-CF35-CI B S iPr O Ph OEt 4-C15-Cl H S iPr O Ph OEt 4-~3r 5-Cl H S iPr O Ph OEt 4-CF35-Br H S iPr O Ph OEt 4-CF35-F H S iPr O Ph OEt - . : . - . : - .~, : . . -, : ~ , .. . ~ : : . . . - : . . :. ., -: . , ZC~:IQ~65 Rl R2 B V ~8 Y' Rl~ Y R
4-CF34-Cl H S iPr O Ph OEt 4-CF34-F N S iPr D Ph OEt 4-CF3 ~ H S iPr O Ph OEt 4-CF35-Cl C02Me S iPr O Ph OEt 4-CF35-Br CO2Me S iPr O Ph OEt 4-CF35-F CO2Me S iPr O Ph OEt 4-CF34-Cl CO2Me S iPr O Ph OEt 4-CF34-F CO2Me S iPr O P~ OEt 4-CF3 H CO2Me S iPr O Ph OEt 4-CF35-Br N O tBu O Et OEt q-C15-Br B O tBu O Et OEt 4-Br 5-Br H O t8u O Et OEt 4-OCF35-Br H O tBu O Et OEt 4-CF35-Cl H O tBu O Et OEt 4-C15-Cl H O tBu O Et OEt 4-8r S-Cl H O tBu O Et OEt 4-CF35-CF3 H O tBu O Et OEt 4-CF34-F H O tBu O Et OEt 4-CF3 H H O tBu O Et OEt 4-CF35-Br CO2Me O tBu O Et OEt 4-CF35-Cl C02Me tBu O Et OEt 4-CF35-CF3 CO2Me O tBu O Et OEt 4-CF34-F CO2Me tBu O Et OEt 4-CF3 H CO2Me O tBu O Et OEt 3 D 4-CF35-Cl H S tBu O Et OEt 4-C15-Cl H S tBu O Et OEt 4-Br 5-Cl H S tBu O Et OEt 4-CF35-Br H S tBu O Et OEt 4-CF35-F H S tBu O Et OEt 4-CF34-Cl H S tBu O Et OEt 4-CF34-F H S tBu O Et OEt ,:. ~ .', ,: . ', ': ' ' - . ' ' : , . ' . ::
: ~, . , . ' ~ ' ,, : , ' .
' ' ' . ': ~ . ' ' ' ' ' , ::
, ,' :' , : ' . " ' ' ~, 6~
Rl R2 B V RB Y' ~10 Y R
4-CF3 H H S t8u O Et . OEt 4-CF35-Cl C02Me S t8u O Et OEt 4-CF35-Br C02Me S tBu O Et OEt 4 CF35 F C02Me S tBu O Et OEt 4-CF34-Cl CO2Me ~ tBu O Et OEt 4 CF34 F COzMe S tBu O Et OEt 4-CF3 H C02Me S tBu O Et OEt 4-C15-Br H O iPr S Et O-iPr 4-Br 5-Br H O iPr S Et OPh 4-OCF35-Br H O iPr S Ph OEt 4-CF3 S-Cl H O iPr S Ph O-iPr 4-C15-Cl H O iPr S Ph OPh 4-Br 5-Cl H O tBu S Et OEt 4-CF35-CF3 H o tBu S Et O-iPr 4-CF34-F H O tBu S Et OPh 4-CF~ H H O tBu S Ph OEt 4-CF35-Br CO2Me O tBu S Ph O-iPr .:
4-CF35-Cl CO2Me O tBu S Ph OPh q-CF35-Br H S iPr S iPr OEt 4-CF35-F H S iPr S iPr O-iPr 4-CF34-Cl H S iPr S iPr OPh 4-CF34-F H S iPr S nPr OEt 4-CF3 H H S iPr S nPr O-iPr 4-CF35-Cl CO2Me S iPr S nPr OPh 4-CF35-Br CO2Me S tBu S Me OEt 4-~F35-F CO2Me S tSu S Me O-;Pr 4-CF34-Cl CO2Me S tBu S Me OPh 4-CF34-F CO2Me S tBu S Me O-~ec-Bu 4-CF3 H C02Me S tBu S Me O-nPr : .
.' ' ., ~ . , . . . .,., . .. ~., . , . ,. , , ~, , , , ,, "
,: - . . - :: - : . . : .. . - :, ~.
XC~ 165 T~bl~_12 U-N ~ R~
~, ,, ' S-P-ORlD
ORl 1 ~'.
Rl R2 BV Rlo Rll 4-CF3 5-Br H O Et Et 4-C1 5-Br HO Et Et 4-Br 5-Br HO Et Et 4-OCF3 5-Br H O Et Et ::~
4-CF3 5-Cl H O Et Et 4-C1 5-Cl HO Et Et 4-Br 5-Cl HO Et Et 4-CF3 5-CF3 H Et Et 4-CF3 q-F HO Et Et 4-CF3 H HO Et Et ~
4-CF~ 5-Br CO2Me O Et Et ~.
4-CF3 5-Cl CO2Me O Et Et '; -' ,: . , "
~ ., ~ , . . . ..
2~ 65 Rl R2 8 V Rlo Rll 4-CF3 5-CF3 C02Me O Et Et 4-CF3 4-F C02Me O Et Et 4-CF3 ~ C2Me O Et Et 4-CF3 5-Cl H S Et Et 4-C1 5-Ci H S Et Et 4-8r 5-Cl H S Et Et 4-CF3 5-Br H S Et Et 4-CF3 S-F H S Et Et 4-CF3 4-Cl H S Et Et 4-CF3 4-F H S Et Et 4-CF3 H H S Et Et 4 CF3 5 Cl C02Me S Et Et 4-CF3 5-Br C02Me S Et Et 4-CF3 S-F C02Me S Et Et 4-CF3 4-Cl C02Me S Et Et 4-CF3 4-F C02Me S Et Et 4-CF3 H C02Me S Et Et 2~ 65 Table 13 '-~
~ N
O S-N-R~
Rl R2 B V R8 R12 : , 4-CF3 5-Br H O nBu nBu 4-Cl S-Br H O nBu nBu 4-Br 5-Br H O nBu nBu 4-OCF3 5-Br H O nBu nBu 4-CF~ 5-Cl H O nBu nBu 4-C1 5-Cl H O nBu nBu 4-Br 5-Cl H O nBu nBu 4-CF3 S-CF3 H nBu nBu 9-CF3 4-F H O nBu nBu 4-C~3 H B O nBu ~Bu 4 CF3 S-Br CO2Me O ~Bu nBu 4-cr3 5-Cl CO2Me O DBu DBu -, 9-CF3 5-CF3 CO2Me O nBu nBu .
:
. .
., . .~ . . . . ... . . . .. . . . .. . .
.: .: : , .: . . - ~ . , .. , .: - ., . ~ . - . . : . ,-2~ iS
Rl R2 B V R8 R12 4-CF34-F CO2Me O nBu nBu 4-CF3 H CO2Me O ~Bu nBu 4-CF35-Cl H S nBu nBu 4-C15-Cl H S nBu ~Bu 4-Br S-Cl H S nBu nBu 4-CF35-Br H S nBu nBu 4-CF35-F H S n9u nBu 4-CF34-Cl ~ S ~Bu ~Bu 4-CF34-F H S nBu nBu lS 4-CF3 H H S nBu nBu 4-CF35-Cl C02Me S nBu nBu 4-CF35-Br CO2Me S ~Bu nBu 4-CF35-F CO2Me S nBu nBu 4-CF34-Cl CO2Me S nBu nBu 4-CF34-F CO2Me S nBu nBu 4-CF3 H CO2Me S nBu nBu 4-CF35-Br H O -CH2CH2CH2cH2~H2-4-Cl S-B~ H O -CH2CH2CH2cH2cH2-4-Br 5-Br H O -CH2CH2CH2c~2cH2-4-OCF35-Br H O -CH2CH2CH2cH2 Q2-4-CF35-C~ H O -CH2CH2CH2cH2cH2 4-Cl S-Cl H O -CH2CH2CH2cH2cH2-4-Br 5-Cl H O -CH2CH2CH2cH2cH2-3.3 -CH2CH2CH2cH2cH2-4-CF34-~ H O -CH2CH2CH2cH2c~2-4-CF3 H N O -CH2CH2CH2cH2cH2-4-CF35-Br CO2Me O -CH2CH2CH2cH2cH2 4-CF35-Cl CO2Me O -CH2CH2CH2c82cH2 4-CF3 5-CF3 CO2Me O -CH2CH2CH2cH2cH2 4-CF3 4-F CO2Me -CH2CH2CH2cH2cH2 4-CF3 H CO2Me O -CH2CH2CH2cH2cH2-4-CF3 5-Cl H S -cN2cH2cH2cH2cH2 , .,.......... : i - - .... - 1~
3Q~6~
Rl R2 B V R8 R12 4-C15-Cl H S -CH2CH2CH2cH2cB2-4-Br 5-Cl H S -CH2CH2CH2CH2CH2-4-CF35-Br H S -CH2CH2CH2cH2cH2-4 CF35 F H S -CH2CH2CH2cH2cH2-4-CF34-Cl H S -CH2CH2CH2cH2cH2-4-CF34-F H S -CH2CH2CH2cH2cH2-4-CF3 H H S -CH2CH2CH2cH2cH2-3 CO2Me S -CH2CH2CH2CH2CH2-4-CP35-Br C02Me S -CH2CH2CH2CH2CH2-4 CF35 F C02Me S -CH2CH2CH2CH2CH2-4-CF34-Cl C02Me S -CH2CH2CH2cH2cH2-4-CF34-F CO2Me S -CH2CH2CH2CH2CH2-4-CF3 H CO2Me S -CH2CH2CH2CH2CH2-4-CF35-9r H O -CH2CH20CH2cH2-4-C15-Br H O -CH2CH20CH2cH2-4-Br 5-Br H O -CH2CH20C~2cH2 4-OCF35-Br H O -CH2cH2cH2cH2-4-CF35-Cl H O -cH2cH2ocH2cH2 4-C15-Cl H O -CH2CH20CH2cH2-4-Br 5-Cl H O -CH2CH20CH2cH2-4-CF35-CF3 H O -CH2cH2cH2cH2 4-CF34-F H O -CH2CH20CH2cH2-4-CF3 H H O -cH2cH2ocH2cH2 4-CF35-Br CO2Me -CH2CH20CH2cH2-4-CF35-Cl CO2Me O -CH2cH2cH2cH2-4-CF35-CF3 CO2Me O -CH2cH2cH2cH2 4-CF34-F CO2Me -cH2cH2ocH2cH2 4-CF3 H CO2Me O -CH2cH2cH2cH2-4-CF35-Cl H S -CH2C~20CH2cH2-4-C15-Cl H S -cH2cH2ocH2cH2 4-Br 5-Cl H S -cN2cH2ocH2cH2-4-CF35-~r H S -CH2CH20C~2cH2-4 CF35-F H S -cH2cH2ocH2cH2 ... . -- ~ ' ' , Q~65 hl R2 8 V R8 R12 4-CF34-Cl ~ S -CH2cH2cH2cH2-4 C~34-F H S -CH2CH20CH2cH2 4-CF3 H H S -C92CH20C~2CH2 4-CF35-Cl CO2Me S -CH2cH2cH2cH2-4-CF35-Br C2Me S -CH2cH2cH2cH2-4 CF35 F C02Me S -CH2cH2cH2cH2-4-CF34-Cl CO2Me S -CH2cH2cH2cH2-4-CF34-F C~2Me S -CH2CH20CB2c~2-4-CF3 H C02Me S -CH2CH20CH2CH2-4-CF35-Br H O -CH2CHMeOCHMeCH2-4-C15-Br H O -CH2CHMeOCHMeCH2-4-Br 5-Br H O -CH2CHMeOCHMeCH2-4-OCF35-Br H O -CH2CNMeOCHMeCH2-4-CF35-Cl H O -CH2CHMeOCHMeCH2-4-C15-Cl H O -CH2CHMeOCHMeCH2-4-Br 5-Cl H O -CH2CHMeOCHMeCH2-4-CF35-CF3 H O -CH2CHMeOCHNeCH2-4-CF34-F H O -CH2CHMeOCHMeCH2-4-CF3 H H O -CH2CHMeOCHMeCH2-4-CF35-Br CO2Me O -CH2CHMeOCHMeCH2-4-CF35-Cl C02Me -CH2CHMeOCHMeCH2-4-CF35-CF3 CO2Me O -CH2CHMeOCHMeCH2-4-CF34-F CO2Me O -CH2CHMeOCHMeCH2-4-CF3 H CO2Me O -CH2CHMeOCHMeCH2-4-CF35-Cl H S -CH2CHMeOCHMeCH2-4-C15-C~ ~ S -CH2CNMeOCHMeCH2-4-Br 5-Cl H S -CH2CHMeOCHMeCH2-4-CF35-Br H S -CH2CHMeOCHMeCN2-4 CF35 F H S -CH2CHMeOC~MeCH2-4-CF34-Cl H S -CH~CHMeOCHMeCH2-4-CF34-F H S -CH2CHMeOCHMeCH2-. . . : . , :. : , ~ " : : : :: ; .
-2C~ 5 _ 1 R2 B V R8 R12 4-CF3 H H S -CH2Cl~eOCHMeCB2-4-CF35-Cl CO2Me S -CH2CHMeOCKMeCH2-4 CF359r CO2Me S -CH2CHMeOCHMeCH2-4-CF35-F CO2Me S -CH2CHMeOCHMeCH2-4-CF34-Cl c~2Me S -CH2CHMeOCHMeCH2-4-CF34-F CO2Me S -CH2CHMeOCHMeCH2-4-CF3 H C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br H O ~t ~yclo-C
4-C15-Br H O Et cyclo-C6H
15 4-Br 5-i3r H O Et cyclo-C6H
4-OCF35-i3r H O Et cyclo-C6H
4-CF35-Cl H O Et cyclo-C6H
4-C15-Cl H O Et cyClo-c6 4-Br 5-Cl H O Et cyclo-C6H
20 4-CF35-CF3 H o Et cyClo-c6 4-CF34-F H O Et c 4-CF3 H H O Et cyClo-c6 4-CF35-Br CO2Me Et cycl3 4-CF35-Cl C02Me Et c 25 4-CF35-CF3 CO2Me O Et CYC1-4-CF34-F CO2Me O Et cyClo-c6 4-CF3 H CO2Me O Et cyclo-c6 4-CF35-Cl H S Et c 4-C15-Cl H S Et c 30 4-Br 5-Cl H S Et cyclo-C6H
4-CF35-Br H S Et cycl~-c6 4-C~35-F H S Et CYC1~
4-CF34-Ci H S Et CYClo-C6Hl 4-CF34-F H S Et CYC1-C6Nl 3S 4-CF3 H H S Et cyclo-C6H
4-CF35-Cl CO2Me S Et CYC1~
...
. .
- "
.; ., .
:. : ~ ~: : :: . . . ..
Z~ 6S
Rl ~2 B V R8 R12 4-CF35-Br CO2Me S Et ~yclo-C6H
4-CF35-F CO2Me S Et ~YCl-4-CF34-Cl CO2Me S Et c 4-CF34-F CO2Me S Et cyclo-C6H
4-CF3 H CO2Me S Et cyC10-c6Hll 4-CF35-Br H O iPr CH2CH2C2Et 4-Cl S-Br H O iPr CN2CH2C2Et 4-Br 5-Br H O iPr Q2CH2CO2Et 4-OCF35-Br H O iPr CH2CH2C2Et 4-CF35-Cl H O iPr CH2CH2C2Et 4-Cl S-Cl H O iPr CH2CH2C02Et 4-Br 5-Cl H O iPr CH2CH2C~2Et 4-CF35-CF3 H O iPr CH2CH2C2Et 4 CF34 F H O iPr CH2CH2C2Et 4-CF3 H H O iPr CHzCH2CO2Et 4-CF35-Br CO2Me iPr CH2CH2C02Et 4-CF35-Cl CO2Me O iPr CH2CH2C02Et 4-CF35-CF3 CO2Me O iPr CH2CH2C2Et 4-CF34-F CO2Me O iPr CH2CH2CO2Et 4-CF3 H CO2Me O iPr CH2CH2C2Et 4-CF35-Cl H S iPr CH2CH2C2Et 4-C15-Cl H S iPr CH2CH2CO2Et 4-Br S-Cl H S iPr CH2CH2C02Et 4-CF35-Br H S iPr CH2CH2C2Et 4-CF35-F H S iPr CH2CH2C2Et 4-CF34-Cl H S iPr CH2CH2C2Et 4-CF34-F H S iPr CH2CH2CO2Et 4-CF3 H H S iPr CH2CH2C2Et 4-CF35-Cl C02Me S iPr CN2CN2C2Et 4-CF35-Br CO2Me S iPr CH2CH2CO2Et 4-CF35-F CO2Me S iPr CH2CH2C2 : .'~
. , . - ,-: ., ~ ,, ... . , , . ,. j, :,, . : .
. : . ,::: ,,: " , , .. . , .:, ,. ,. .. : . : ... ::. ~ ,, .~ . . : . . : . . . :
, . ','' ' ~ ' ' ' ' ' ';', ' , '.' ' ', ',' " ''," '" ". ,' '' ' ' "' ' ' .' ,', " ''"' ' ,. "' , ' ', ' 2~3~65 Rl R2 B V RB R12 .
4 CF3 4 Cl C2Me S iPr CH2CH2CO2Et ..
4-CF3 4-F CO2Me S iPr CH2CH2C2Et 4-CF3 H CO2Me S . iPr CH2CH2C2Et , ': . ' . ', ';, ' ' . ' . ' ' . . . , ' ' , ~. ., ': ~ ' . ` , " . . ' , " , : " ~ . ' , ' ' ' .. , .. : .. ', . .'.. , ., ', ,'; . ,- . ' ' .. '', ' ' : . .... ~ " ', . ' '.'. ' ' :' " . ' ' . ' ', ,, .'.'. ', : ' , , ' : ,"' ' , :' .. ' ' .'.'~ . ', ' ' '.' .,: ' ' " . ', . "
f -Z~ Q~6~
130 ~:~
Table 14 R~ ~ N-N ~ R
~ N
S-SRlD
:.
Rl R2 B V Rlo . -4-CF3 5-Br H O tBu 4-C1 5-Br H O tBu 4-Br 5-Br H O tBu 4-OCF3 5-Br H O tBu 4-CF3 5-Cl H O tBu ~ ~' 4-C1 5-Cl H O tBu ;
4-Br 5-Cl H O tBu 4-CF3 5-CF3 H O tBu 4-CF3 4-F H O tBu 4-CF3 H H O tBu 4-CF3 5-Br CO2Me tBu 4-CF3 5-Cl CO2Me O tBu 4-CF3 5-CF3 CO2Me O tBu .
4-CF3 4-F CO2Me tBu .- . . . . - -- .. .. . .. . . . . .. . . . .. . . ., . . . . . . , . . -. ,. : - .
.,.. , . ... ., , . ~ , i , ; - , . .. , .,:, . . - . - : - . -2~3Q,~6~
_Rl R2 B V Rlo 4-CF3 H C02Me O tBu 4-CF35-Cl H S tBu 4-C15-Cl H S tBu 4-Br 5-Cl H S t8u :;
4-CF35-Br H S tBu ::
4-CF35-F H S tBu 4-CF34-Cl H S tBu 4-CF34-~ H S tBu 4-CF3 H H S tBu 4-CF35-Cl CO2Me S tBu 4-CF35-Br CO2Me S tBu 4-CF35-F CO2Me S t8u 4-CF34-Cl CO2Me S tBu 4-CF34-F CO2Me S tBu 4-CF3 H CO2Me S tBu 4-Br 5-Cl H S 6ec-Bu 4-CF35-Br H S sec-Bu 4-CF35-F H S sec-Bu 4-CF34-Cl H S rec-Bu 4-CF34-F H S cec-Bu 4-CF3 H H S ~ec-Bu 4-CF35-C~ CO2Me S ~ec-Bu 4-CF35-Br CO2Me S bec-Bu 4-CF35-F CO2Me S ~ec-Bu 3û 4-CF34-Cl CO2Me S cec-Bu 4-CF34-F CO2Me S ~ec-Bu 4-CF3 N CO2Me S ~ec-8u 4-CF35-Br H O Ph 4-C15-Br H O Ph 4-Br 5-i3r H O Ph 4-OCF35-Br H O Ph ~-:
.
' .
.-. . . , . : .: . - ~ . . -:: - -,' - : - . ~ . , . . :: ' - - . .: ::: : : ~ , :
Z~ 65 Rl R2 B V Rlo - .
4-CF3 5-Cl ~ O Ph 4-Cl S-Cl H O Ph 4-Br 5-Cl H O Ph 4-CF3 5-CF3 H o Ph 4-CF3 4-F H O Ph 4-CF3 H H O Ph ~-CF3 S-Br CO2Me Ph 4-CF3 5-Cl CO~Ne O Ph 4-CF3 5-CF3 CO2Me O Ph 4-CF3 4-F C2Me O Ph 4-CF3 H CO2Me Ph 4-CF3 5-Cl H S Ph 4-Cl S-Cl H S Ph ~.
4-Br 5-Cl H S Ph 20 4-CF3 5-Fr H S Ph 4-CF3 5-F H S Ph 4-CF3 4-Cl H S Ph 4-CF3 4-F H S Ph 4-CF3 H H S Ph 25 4-CF3 5-Cl CO2Me S Ph 4-CF3 S-Br CO2Me S Ph .
4-CF3 5-F CO2Me S Ph 4-CF3 4-Cl CO2Me S Ph 4 CF3 4-F CO2Me S Ph :;
4-CF3 H C02Me S Ph 4-CF3 5-Br H O 4-Cl-Ph 4-C1 5-Br H O 4-Cl-~h 4-Br 5-Br H O 4-Cl-Ph 4-OCF3 5-Br H O 4-Cl-Ph 4-CF3 5-Cl H O 4-Cl-Ph 4-C1 5-Cl H O 4-Cl-Ph , . -.: - . ~ . . - : . - .
Z~ 65 133 :
Rl R2 B V Rlo -4-Br 5-Cl H . 0 4-Cl-Ph 4-CF35-CF3 H 0 4-Cl-Ph 4-CF34-F H 0 4-Cl-Ph 4-CF3 ~ H 0 4-Cl-Ph 10 4-CF35-~r C02Me 4-Cl-Ph 4-CF35-Cl C02Me O 4-Cl-Ph 4-CF35-CF3 C02Me O 4-Cl-Ph 4-CF34-F C02Me 4-Cl-Ph 4-CF3 ~ C02Me g-Cl-Ph 15 4-CF35-Cl H S 4-Cl-Ph 4-C15-Cl H S 4-Cl-Ph . , 4-Br 5-Cl H S 4-Cl-Ph 4-CF35-Br H S 4-Cl-Ph 4-CF35-F H S 4-Cl-Ph 20 4-CF34-Cl H S 4-Cl-Ph 4-CF34-F H S 4-Cl-Ph 4-CF3 H H S 4-Cl-Ph 4-CF35 Cl C02Me S 4-Cl-Ph 4-CF35-Br C02Me S 4-Cl-Ph 25 4-CF35-F C02Me S 4-Cl-Ph 4-CF34-Cl COzMe S 4-Cl-Ph 4-CF34-F C02Me S 4-Cl-Ph 4-CF3 H C02Me S 4-Cl-Ph . ,: ' ' - :,, .. : .: . : . - : . : ,: - ~., . :
.. ~ . . . .
~ble 15 11 5~RI3 ~ N O
S -N ~ `.
~ Rg R1 R R13a R13b V R8 ~9 ~ :
4-CF3 5-F Me Me S Me OEt 4-CF3 5-Cl Me Me S Me OEt 4-CF3 4-F Me Me S Me OEt 4-CF3 5-Br Ph H O Me OEt '. -4-CF3 5-Br C02Me H O Me OEt 4-CF3 5-Br Me ~e O Me OEt 4-CF3 5-Cl Me Me O Me OEt 4-CF3 5-F Me Me S Me O-nBu l~ .
4-CF3 5-C1 Me Me S Me O-nBu 4-CF3 4-~ Me Me S Me O-DBu -4-CF~ S-Br Pb H O Me O-~Bu .
4-CF3 5-Br C02Me H O Me O-n8u 4-CF3 5-~r Me Me O Me 0-~9u 3~ ~-CF3 5-Cl Ne Me O Me O-nBu : .
''' '". ' ~'.
Z~!0~6~
Rl R2 pl3a pl3b V R~ Rg 4-CF35-F Me Me S Me 0-nHexyl 4-CF35-Cl Me Me S Me 0-nHe~yl 4-CF34-F Me Me S Me 0-nHe~yl 4-C~35-Br Ph H 0 Me 0-nHexyl 10 4-CF35-Br C02Me H 0 Me 0-nHe~yl 4-CF35-Br Me Me 0 Me 0-nHe~yl 4-CF35-Cl Me Me 0 Me 0-nHe~yl 4-CF35-F Me Me S Me 0-~ec-Bu 4-CF35-Cl Me Me S Me 0-~ec-Bu 15 4-CF34-F Me Me S Me 0-~ec-Bu 4-CF35-Br Ph H 0 Me 0-6ec-Bu 4-CF35-Br C02Me H 0 Me 0-6ec-Bu 4-CF35-Br Me Me 0 Me 0-6ec-Bu 4-CF35-Cl Me Me 0 Me 0-sec-Bu 20 4-CF35-F Me Me S Me 0-iPr 4-CF35-Cl Me Me S Me 0-iPr 4-CF34-F Me Me S Me 0-iPr 4-CF35-Br Ph H 0 Me 0-iPr 4-CF35-~r C02Me H 0 Me 0-iPr 25 4-CF35-Br Me Me 0 Me 0-iPr 4-CF35-Cl Me Me 0 Me 0-iPr 4 CF35-F Me Me S Me OCH2CH20Et 4-CF35-Cl Me Me S Me OCH2CH20Et 4-~F34-F Me Me S Me 0CH2CH20Et 4-CF35-Br Ph H 0 Me OCH2CH20Et 4-CF35-~r C02Me H 0 Me OCH2CH20Et 4-CF35-Br Me Me 0 Me OCH2CH20Et 4-CF35-Cl Me Me 0 Me OCH2CH20Et 4-CF35-F Me Me. S Me F
4-CF35-Cl Me Me S Me F
4-CF34-F Me Me S Me F
';, ':
' ':
, - . ~ : : -:: . . ~ , . , .. . ~, , .. . . .-:
~ . , . :~, : . :: : . . -~C~0~65 Rl R2 pl3a pl3b V RB Rg 4-CF3 5-Br Ph H O Me F
4-CF3 5-Br C02Me H O Me F
4-CF3 5-~r ~e Me O Me F ~.
4-CF35-Cl ~e Ne O Me F
4-CF35-F Me Me S Me NMe2 4-CF3 5-Cl Me Me S Me NMe2 4-CF34-F Me Me S Me NMe2 4-CF3 5-Br Ph N O Me NMe2 4-CF3 S-}lr C02Me H 0 Me NMe2 4-CF3 5-~r Me Me O Me NMe2 4-CF3 5-Cl Me Me O Me NMe2 .
4-CF3 5-F Me Me S Et O-iPr ' 4-CF3 5-Cl Me Me S Et O-iPr 4-CF34-F Me Me S Et O-iPr : .:
4-CF3 5-Br Ph H O Et O-iPr 4-CF3 5-Br C02Me H O Et O-iPr , i .
4-CF3 5-Br Me Me O Et O-iPr 4-CF3 5-Cl Me Me O Et O-iPr .: .
4-CF35-F Me Me S iPr OEt .
4-CF35-Cl Me Me S iPr OEt 4-CF34-F Me Me S iPr OEt 4-CF3 5-Br Ph H O iPr OEt 4-CF3 5-Br C02Me H O iPr OEt 4-CF35-Br Me Me O iPr OEt 4-CF 5-Cl Me Me O iPr OEt 4-CF35-F Me Me S ~Pr OCH2CF3 4-CF35-Cl Me Me S ~Pr OCH2CF3 ,.
4-CF34-F Me Me S iPr OCH2CF3 ;
4-CF3 5-Br Ph H O lPr OCH2CF3 4-CF3 5-Br C02Me H O iPr OCHzCF3 4-CF3 5-Br Me Me O iPr OCH2CF3 ~:~
- , . .. . .
. . : ~
2~ L6~;
Rl R2 R 3a R b V R8 Rg S
4-CF3 5-Cl Me Me O iPr OCN2CF3 4 CF3 S F Me Me S ~Pr OCH2CO2Me 4-CF3 5-Cl Me Me S iPr OCH2CO2Me 4-CF3 4-F Me Me S iPr OCH2CO2Me 4-CF3 5-Br Ph H O iPr OCH2CO2Me 4-CF3 5-9r CO2Ne H O iPr OCH2CO2Me 4-CF3 S-Br Me Me O iPr OCH2CO2Me 4-CF3 5-Cl Me Me O iPr OCH2CO2Me ', ..
I~ble 16 R2 ~R3 .:~
~ ' ;' '' ~' S~ ~
~ ~9 Rfl Rl R2 R3 RB Rg 4-CF3 4-Cl H Me OEt 4-C1 4-Cl H Me OEt 4-B~ 4-Cl H Me GEt 4-OCF3 4-Cl H Me OEt 4-OCF2H 4-Cl H Me OEt ' 2 ( )2 4-Cl ~ Me OEt 4-CF3 4-F H Me OEt 4-C1 4-F H Me OEt 4-Br 4-F B Me OEt 4-OCF3 4-F H Me OEt 4-OC~2H 4-F H Me OEt 3,4-CH2C(Me~2O 4-F H Me OEt ~1 R2 R3 ~8 Rg -. :
4-CF3 4-OCF2H H Me OEt 4-C1 4-OCF2H H Me OEt 4-8r 4-OCF2H H Me OEt 4-OCF3 4-ocF2a H Me OEt 0 4-OCF2H 4-OCF2H H Me OEt 3,4-CH2C(Me)20 4-OCF H N Me OEt 4-CF3 4-Br H Me OEt 4-CF3 4-C1 4-Cl Me OEt 4-C1 4-C1 4-Cl Me OEt 4-Br 4-C1 4-Cl Me OEt 4-OCF3 4-C1 4-Cl Me OEt 4-OCF2H 4-C1 4-Cl Me OEt 3,4-CH2C(Me)20 4-C1 4-Cl Me OEt 4-CF3 4-F 4-Cl Me OEt 4-OCF3 4-F 4-Cl Me OEt .-4-CF3 4-OCF2H 4-Cl Me OEt 4-OCF3 4-OCF2H 4-Cl Me OEt 4-CF3 4-C1 4-CN Me OEt 4-C1 4-C1 4-CN Me OEt 4-OCF3 4-C1 4-CN Me OEt 2S 4-CF3 4-F 4-CN Me OEt . .
4-OCF3 4-F 4_CN ~e OEt 4-CF3 4-C1 4-CO2Me Me OEt 4-CF3 q-Cl H Me O-n-Bu 4-OCF3 4-Cl H Me O-n-Bu 4-CF3 4-F H Me O-n-Bu 4-OCF3 4-F H . Me O-n-Bu 3,4-CH2C(Me)20 4-F H Me O-n-Bu 4-CF3 4-OCF2H H Me O-n-Bu 4-C~ 4-OCF2H H Me O-n-Bu 4-B~ 4-OCF2H H Me ' O-n-Bu - . : . . - , ,- : . :, - , , :: :: . , , . .:
- - . -, - - .. , , . : .. . .: : .
., ~ : , .. . . ..
:,. . ..
Rl R2 R3 R8 Rg . ';
4-OCF3 4-OCF2H 8 Me O-n-Bu 4-CF3 4-Br H Me O-n-13u 4-CF3 4-C1 4-Cl Me O-n-Bu 4-Sl 4-C1 4-Cl Me O-n-Bu 4-Br 4-C1 4-Cl Me O-n-Bu 4-OCF3 4-C1 4-Cl Me O-n-Bu 4-CF3 4-F 4-Cl Me O-n-Bu .
4-OCF3 4-F 4-Cl Me O-n-~u :.
4-CF3 4-OCF2R 4-Cl Me O-n-Bu 4-C1 4-OCF2B 4-Cl Me O-n-Bu 4-Br 4-OCF2H 4-Cl Me O-n-Bu 4-OCF3 4-OCF2H 4-Cl Me O-n-Bu 4-CF3 4-C1 4-CN Me O-n-Bu 4-OCF3 4-C1 4-CN Me O-n-Bu 4-CF3 4-F 4-CN Me O-n-Bu 4-OCF3 4-F 4-CN Me O-n-Bu 4-CF3 4-C1 4-C02Me Me O-n-Bu 4-CF3 4-OMe 4-Cl Me O-n-Bu 4-C1 4-OPh 4-Cl Me O-n-Bu 4-Br 4-SCF2H 4-Cl Me O-D-8U
4-OCF3 4-N02 4-Cl Me O-n-Bu 4-OCF2H 4-SMe 4-Cl Me O-n-Bu 3,4-CH2C(Me)20 4-S02Me 4-Cl Me O-n-Bu 4-CF3 4-CN 4-Cl Me O-n-Bu 4-C1 3-C1 4-Cl Me O-n-Bu 4-i3r 3-F 4-Cl Me O-n-Bu 4-OCF3 4-Me 4-Cl Me O-n-Bu 4-OCF2H 4-allyl 4-Cl Me O-n-Bu 3,4-C~2C(Me)20 4-CF3 4-Cl Me O-D-Bu 4-CF3 4-C1 4-C02Et Me 0-~-9u ~.
, . : . ., ,. - . .::
- .. . , .: - :
.
- ' - - . .
~lQlQ~65 Rl R2 R3 R8 Rg 4-C1 4-C1 4-OMe Me O-n-Bu 4-Br 4-C1 2 2 O-n-Bu 4-OCF3 4-C1 4-OCF2CF2H Me O-n-Bu 4-OCF2H 4-Cl 4-OPh Me O-n-Bu 3,4-CH2C(Me)20 4-CF3 4-CF3 Me O-n-Bu 4-CF3 4-C1 4-CF3 Me O-n-8u 4-C1 4-C1 4-Me Me O-n-Bu 4-Br 4-C1 3-Cl Me O-~-Bu 4-OCF3 4-C1 3 Br Me O-n-Bu 4-OCF2H 4-C1 4-NO2 Me O-D-BU
4-CF3 4-Cl H Me O-n-he~yl 4-CF3 4-F H Me O-n-hexyl 4-C~3 4-OCF2H H Me O-n-h~yl .
4-OCF3 4-OCF2H H Me O-n-octyl 4-CF3 4-Br H Me O-n-octyl 4-CF3 4-C1 4-Cl Me O-n-octyl `
4-C1 4-C1 4-Cl Me O-n-octyl 4-Br 4-C1 4-Cl Me O-n-octyl 4-OCF3 4-C1 4-Cl Me O-n-octyl 4-CF3 4-F 4-Cl Me O-n-decyl 4-C1 4-F 4-Cl Me O-n-decyl 4-OCF3 4-F 4-Cl Me O-n-decyl 4-CF3 4-OCF2H 4-Cl Me O-n-decyl 4-OCF3 4-OCF2H 4-Cl Me O-n-decyl 4-CF3 4-C1 4-CN Me O-n-decyl - 4-C1 4-C1 4-CN Me O-n-decyl 4-Br 9-Cl 4-~ Me O-n-decyl 4-OCF3 4-C1 4-CN Me O-n-dodecyl .~:
4-CF3 4-F 4-CN Me O-n-aodecyl 4-GCF3 4-F 4-CN Me O-n-dodecyl 4-CF3 4-C1 4-CO2Me Me O-n-dodecyl 4-CF3 4-Cl H Me O-sec-Bu 4-C1 4-Cl H Me O-sec-Bu :-. . .
,",." ,, ,, ~ "
.. .. ' ; ., . . . , . . ', . . . .. ' ' , . . , ., . ~ . ' ' ' :
ZCl(;~Q165 Rl R2 R3 R8 Rg S .
4-OCF3 4-Cl H Me O-cec-Bu 4-CF3 4-F H Me O-sec-Fu 4-OCF3 4-F H Me O-sec-Bu 4-CF3 4-OCF2H H Me O-rec-~u 4-OCF3 4-OCF2H H Me O-sec-Bu 4-CF3 4-Br H Me 0-6ec-Bu 4-CF3 4-C1 4-Cl Me O-sec-Bu 4-C1 4-C1 4-Cl Me O-sec-Bu 4-Br 4-C1 4-Cl Me O-~ec-Bu 4-OCF3 4-C1 4-Cl Me O-sec-Bu 4-CF3 4-F 4-Cl Me O-sec-Bu 4-C1 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me O-sec-Bu 4-CF3 4-OCF2H 4-Cl Me O-sec-Bu 4-OCF3 4-OCF2H 4-Cl Me O-sec-Bu 4-CF3 4-C1 4-CN Me O-sec-Bu 4-C1 4-C1 4-CN Me O-sec-Bu 4-OCF3 4-C1 4-CN Me O-sec-Bu 4-CF3 4-F 4-CN Me O-sec-Bu 4-OCF3 4-F 4-CN Me O--ec-Bu 4-CF3 4-C1 4-C02Me Me O-cec-Bu 4-CF3 4-CN 4-Cl Me O-~ec-Bu 4-C1 3-C1 4-Cl Me O-sec-Bu 4-Br 3-F 4-Cl Me O-sec-Bu 4-OCF3 4-Me 4-Cl Me O-sec-Bu 4-CF3 4-C1 4-C02Et Me O-sec-Bu 4-C1 4-C1 4-OMe Me O-cec-Bu 4-Br 4-C1 2 2 O-sec-Bu 4-OCF3 4-C1 4-OCF2CF2B Me O-sec-Bu 4-OCF2 4-C1 4-OPh ~e O-~ec-Bu 3,4-CH2C~Me)20 4-C1 4-CF3 Me O-~ec-Bu 4-CF3 4-C1 4-CF3 Me 0-6ec-Bu 4-C1 4-C1 4-Me Me O-sec-Bu . : - -. . . : . : . : . - . :.:, , .
2C~ 6~
Rl R2 R3 RB Rg .
4--Br 4-C1 3-Cl Me 0-6ec-Bu :
4-OCF3 4-C1 3-Br Me O-sec-Bu 4-OCF2H ~-Cl 4-No2 Me 0-6ec-Bu 4-CF3 4-Cl H Me O-iPr 4-OCF3 4-Cl H Me O-iPr 4-CF3 4-F H Me O-iPr 4-OCF3 4-F H Me O-iPr 4-CF3 4-OCF2N B Me O-iPr 4-OCF3 4-OCF2H H Me O-iPr 4-CF3 4-Br H Me O-iPr 4-OCF3 4-8r H Me O-iPr 4-CF3 4-C1 4-Cl Me O-iPr 4-OCF3 4-C1 4-Cl Me O-lPr 4-CF3 4-F 4-Cl Me O-iPr 4-OCF3 4-F 4-Cl Me O-iPr 4-CF3 4-C1 4-CN Me O-iPr 4-OCF3 4-C1 4-CN Me O-iPr 4-CF3 4-F 4-CN Me O-iPr 4-OCF3 4-F 4-CN Me O-iPr ~-CF3 4-Cl q-C02Me Me O-iPr 4-CF3 4-Cl H Me CH2c~2Et 4-CF3 4-F H Me OCH2CB20Et 4-CF3 4-OCF2H H Me OCH2CH20Et 4-OCF3 4-OCF2H H Me OCH2Ccl3 .:
4-CF3 4-Br H Me 2 3 ~::
4-CF3 4-C1 4-Cl Me OCH2ccl3 4-C1 4-C1 4-Cl Me OCH2CC1 4-OCF3 4-C1 9-Cl Me oCH2CC13 ,~
4-CF3 4-F 4-Cl Me ~CH2CF3 ~' 4-OCF3 4-F 4-Cl Me 2 3 4-CF3 4-OCF2H 4-Cl Me 2 3 :
Rl R2 R3 R8 Rg ::~
i-oCF3 4-OCF2H q-Cl Me CH2cF3 4-CF3 4-C1 4-CN Me 2 3 4-OCF3 4-C1 4-CN Me OCH2CO2Et 4-CF3 4-F 4-CN Me OCH2CO2Et 4-OCF3 4-F 4-CN Me OCH2CO2Et 4-C~3 4-C1 4-CO2Me Me OCH2CO2Et 4-CF3 4-Cl H Me F
4-C1 4-Cl ~ Me F
4-OCF3 4-Cl H Me F ~:
4-CF3 4-F H Me F
4-OCF3 4-F H Me F
4-CF3 4-OCF2H H Me F
4-OCF3 4-OCF2H H Me NMe2 4-CF3 4-Br H Me 2 4-CF3 4-C1 4-Cl Me 2 4-C1 4-C1 4-C1 Me NMe2 4-OCF3 4-C1 4-Cl Me NMe2 4-CF3 4-F 4-C1 Me N~t2 4-OCF3 4-F 4-Cl Me 2 4-CF3 4-OCF2H 4-Cl Me piperidino 4-OCF3 4-OCF2H 4-Cl Me morpholino ~.
4-CF3 4-C1 4-CN Me n-Pr 4-OCF3 4-C1 4-CN Me n-Pr 4-CF3 4-F 4-CN Me Sec-Bu 4-OCF3 4-F 4-CN Me 4-Cl-Ph 4-CF3 4-C1 4-CO2Me Me Ph 4-CF3 4-Cl H Et O-~Pr 4-C1 4-Cl H Et O-iPr 4-OCF3 4-Cl H Et O-iPr 4-CF3 4-F H Et O-i~r 4-OCF3 4-F H Et O-lPr :~
4-CF3 4-OCF2H H Et O-iPr :' :- , .. ~ .. , :. . . - .,: " :: . . ... ,, .- i.. :.,.. :, .... .. . .. . ... ..
. : . - , . . : -,, : ,' -- ~:
Z6~ 65 Rl R2 R3 R8 Rg S
4-OCF3 ~-OCF2H H Et O-~Pr 4-CF3 4-Br H Et O-iPr 4-CF3 4-C1 4-Cl Et O-~Pr 4-OCF3 4-C1 4-Cl Et 9-iPr 4-CF3 4-F 4-Cl Et OEt 4-OCF3 4-F 4-Cl Et OEt 4-CF3 4-OCF2H 4-Cl Et OCH2CC13 4-OCF3 4-OCF2H 4-Cl Et 2 4-CF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-OCF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-F 4-CN Et aPr 4-OCF3 4-F 4-CN Et Ph 3,4-CH2C(Me)2O 4-F 4-CN Et Ph 4-CF3 4-Cl H iPr OEt 4-OCF3 4-Cl B iPr OEt 4-CF3 4-F H iPr OEt .
4-CF3 4-OCF2H H iPr OEt 4-OCF3 4-OCF2H H iPr OEt 4-CF3 4-Br H iPr OEt 4-CF3 4-C1 4-Cl iPr OEt 4-C1 4-C1 4-Cl iPr OEt 4-Br 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt 4-CF3 4-F 4-Cl ~Pr OEt 4-OCF3 4-F 4-Cl iPr OEt 4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2H 4-Cl iPr OEt 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt 4-CF3 4-F 4-CN iPr OEt ~. .
. ' .':' -2~1~Q~65 Rl R2 R3 R8 Rg 4-OCF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt 4-CF3 ~-CN 4-Cl iPr OEt 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt 4-OCF3 4-Me 4-Cl iPr OEt .
4-OCFzH 4-o-~llyl 4-Cl iPr OEt 3,4-CH2C(Me)2O 4-CF3 4-Cl iPr OEt 4-CF3 4-C1 4-CO2Et iPr OEt 4-C1 4-Cl 4-OMe iPr OEt 4-Br 4-C1 4-SCF2CF2H iPr OEt 4-OCF3 4-C1 2 2 iPr OEt 4-OCF2H 4-C1 4-OPh iPr OEt .
3,4-CH2C(Me)2O 4-C1 4-CF3 iPr OEt 4-C~3 4-C1 4-CF3 iPr OEt 4-Br 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-C1 4-No2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu 4-C1 4-Cl H iPr O-n-Bu 4-Br 4-Cl H iPr O-n-Bu 4-OCF3 4-Cl H ~Pr O-D-Bu 4-CF3 4-F H iPr O-D-Bu -4-OCF3 - 4-F H iPr O-n-9u 4-CF3 4-OCF2H N iPr O-n-Bu 4-OCF 4-OCF2H H iPr O-n-Bu 4-CF3 4-Br H iPr O-n-Bu 4-CF3 4-C1 4-Cl iPr O-n-Bu 4-Br 4-C1 4-Cl iPr O-n-Bu 4-OCF3 4-C1 4-Cl iPr O-n-Bu 4-CF3 4-F 4-Cl iPr OCH2CF3 , , - -:
:: ~
2~ 65 Rl R2 R3 RB R9 4-OCF3 4-F 4-Cl iPr 2 3 4-CF3 4-OCF2H . 4-Cl iPr 2 2 4-OCF3 4-OCF2H 4-Cl iPr 2 4-CF3 4-Cl 4-CN iPr 4-OCF3 4-C1 4-CN iPr 2 4-CF3 4-F 4-CN iPr piperidino 4-OCF3 4-F 4-CN iPr Et 4-CF3 4-C1 4-CO2Me iPr Ph 3,4-CH2C(Me)zO 4-C1 4-CO2Me iPr Ph 4-CF3 4-Cl H CH2Ph OEt 4-CF3 4-OCF2H H C~2Ph piperidino ,,~ :
9-CF3 4-Br H CH Ph OCH2CH20Et 4-CF3 4-C1 4-Cl CH2Ph Me ~i ' "
~'' . ~:
.~: .
~, . '~ .
Z~I~Q~L65 ~able 17 Rz ~ J
O ~ N ~ ' S
15~ -~S -R~
R~ O
~, R1 R2 R3 R8 Rg ..
.
4-CF3 4-Cl H MeNMe2 4-OCF3 4-Cl N MeNMe2 4-CF3 4-F H Me 2 4-OCF3 4-F H MeNMe2 4-CF3 4-OCF2H H Me 2 4-OCF3 4-OCF2H H Me 2 4-CF3 4-C1 4-Cl Me 2 ;
4-C1 4-C1 4-Cl MeNMe2 4-Br 4-C1 4-Cl MeNMe2 4-OCF3 4-C1 4-Cl MeNMe2 4-CF3 4-F 4-Cl Me . 2-. , .
.. .. , . . ~ : : . .. . -:
Q~165 Rl a2 R3 R~3 R9 4-OCF3 ~-~ 4-Cl Me NMe2 4-CF3 4-OCF2H 4-Cl Me NMe2 4-OCF3 4-OCF2H 4-~1 Me NMe2 !~
4-CF3 4-Cl 4-CN Me NMe2 4-C1 4-C1 4-CN Me NMe2 4-Br 4-C1 4-CN Me NMe2 4-OCF3 4-Cl 4-CN Me NMe2 4-CF3 4-F 4-CN Me NMe2 4-OCF3 4-F 4-C~ Me 2 4-CF3 4-C1 2 NMe2 4-CF3 4-Cl H Me NEt2 3,4-CH2C(Me)2~ 4-Cl H Me 2 9-CF3 ~-F H Me 2 4-OCF3 ~-F H Me NEt2 4-CF3 ~.4-DCF2H H Me NEt2 4-OCF3 ~-OCF2H H Me NEt2 4-CF3 4-~r H Me N 2 3,4-CH2C(Me)20 4-Ur H Me 2 4-CF3 Ç-~l 4-Cl Me NEt2 4-C1 4-C1 4-Cl Me 2 4-~r 4-C1 4-Cl Me NEt2 4-OCF3 4-C1 4-Cl Me 2 4-CF3 4-'F 4-Cl Me 2 ~
4-OCF3 ~-F 4-Cl Me NEt2 ~ "
4-CF 4-~CF2H 4-Cl Me 2 . ~ f 4-ocr3 4-OCF2H 4-Cl Me NEt2 4-OCF2H ~-~CF2N 4-Cl Me NEt `~
3,4-CH2C(Me)20 4-OCF2H 4-Cl Me 2 4-CF3 4-C1 4_CN Me 2 4-OCF3 4_Cl 4-CN Me 2 "
, : : . . : . . . ...... . . . . - . -: .
: ,, , .: : . :., .: ,. , .. , : . . :
'~: , ' :. . ' :'.:. ~' . ~ .' ... ' ' - ' ' .' ' ' 2C~C~6S
Rl R2 R3 R8 Rg S
4-CF3 4-F 4-CN Me 2 4-OCF3 4-F 4-CN Me NEt2 4-CF3 4-C1 2 NEt2 4-CF3 4-CI H Me piperidino 4-OCF3 4-Cl H Me piperidi~o 4-CF3 4-F H Me Sec-Bu 4-OCF3 4-F ~ Me n-~e~yl 4-CF3 4-OCF2H H Me Ph :
4-OCF3 4-OCF2H H Me Ph 4-CF3 4-Br H Me 4-Cl-Ph 4-C1 4-Pr H Me 4-Cl-Ph 4-CF3 4-C1 4-Cl Me n-Bu 4-C1 4-C1 4-Cl Me n-Bu 4-Br 4-C1 4-Cl Me n-Bu 4-OCF3 4-C1 4-Cl Me n-Bu 4-CF3 4-F 4-Cl Et N 2 .;.-4-OCF3 4-F 4-Cl Et NMÇ2 4-CF3 4-OCF2H 4-Cl Et NEt2 4-OCF3 4-OCF2H 4-Cl Et morpholino 4-CF3 4-C1 4-CN Et iPr 3,4-CH2C(Me)2O 4-C1 4-CN Et D-Bu 4-CF3 4-F 4-CN Et n-Bu . ,-.
4-CF3 4-C1 2 4-MeO-Ph 4-CF3 4-Cl H iPr 2 4-CI 4-Cl N iPr 2 4-Br 4-Cl H iPr ~Me2 4-OCF3 4-Cl H iPr 2 :.
4-CF3 4-F H iPr NMe2 4-OCF3 4-F H iPr e2 ' ..
4-CF3 4-OCF2H H ~Pr NMe2 4-OCF3 4-OCF2H H iPr 2 ' .' ' ' '' ' " .. : " . ' " ' , ' : ': ' ' 2~0Q~65 !`:
Rl R2 ~3 R8 Rg 3,4-CH2C(Me)20 4-oCF2H H iPr NMe2 4-CF3 4-Br ~ iPr NMe2 4-CF3 4-C1 4-Cl iPr 2 4-C1 4-C1 4-Cl iPr NMe2 4-Br 4-C1 4-Cl iPr NMe2 ~-OCF3 4-C1 4-CI iPr 2 4-CF3 4-F 4-Cl iPr NSt2 4-OCF3 4-F 4-Cl iPr NEt2 4-CF3 4-OCF2N 4-Cl iPr 2,6-di-Me-morpholino 4-OCF3 4-OCF2H 4-Cl iPr piperidino 4-CF3 4-C1 4-CN iPr Et 4-OCF3 4-C1 4-CN iPr Et 4-CF3 4-F 4-CN iPr n-Bu 4-OCF3 4-F 4-CN iPr Ph zo ~-Cr3 ~-Cl 4-C02~e Irr ~_CI_rh 25: ~ :
. . . . , : . ,,, . ~ . . . :,.. :: , . : : , 2~ 6~
~able 18 l0Rz ~ R3 0~
l5S ~ -P-Y1Rlo Ra Y R1l Rl R2 R3 R8 yl YlRlo YlRll 4-CF3 4-Cl H tBu S OEt OEt 4-OCF3 4-Cl H tBu S OEt OEt 4-CF3 4-E H tBu S OEt OEt 4-OCF3 4-F H tBu S OEt OEt 4-CF3 4-OCF2H H tBu S OEt OEt 4-OCF3 4-OCF2H H t8u S OEt OEt 4-CF3 4-Br N tBu S OEt OEt 4-CF3 4-Cl 4-Cl tBu S OEt OEt 4-CI 4-Cl 4-Cl tBu S OEt OEt 4-Br 4-Cl 4-Cl tBu S OEt OEt 4-OCF3 4-Cl 4-Cl tBu S OSt OEt 4-CF3 4-F 4-Cl tBu S OEt OEt .
4-OCF3 4-F 4-Cl tBu S OEt OEt 4-CF3 4-OCF2N 4-Cl tBu S OEt OEt 4-Br 4-OCF2H 4-Cl tBu S OEt OEt i ::.
2~ 16S
Rl R2 R3 R8 yl Y1Rlo YlRll 4-OCF3 4-OCF2H 4-Cl tBu S OEt OEt 4-CF3 4-C1 4-CN tBu S OEt OEt 4-OCF3 4-C1 4-CN tBu S OEt OEt 4-CF3 4-F 4-CN tBu S OEt OEt 4-OCF3 4-F 4-CN tBu S OEt OEt 4-CF3 4-C1 4-CO2Me t8u S OEt OEt 4-CF3 4-Cl H tBu S OCH2C(Me)2CH2O
q-OCF3 4-Cl ~ t~u S OCH2C(Me)2CH2O
4-CF3 4-F H tBu S OCH2C(Me)2C~2O
4-C1 4-F H tBu S OCH2C(Me)2CH2O
4-OCF3 4-F H tBu S OCH2C(Me)2CH2O
4-CF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-OCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-CF3 4-CI 4-Cl tBu S OCH2C(Me)2CH2O
4-C1 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-Br 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-F 4-Cl tBu S oCH2C(Me)2CH2O
4-CF3 4-OCF2H 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 2 tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-CN tBu S OCH2C(Me)2cH2O
4-CF3 4-F 4-CN tBu S OCH2C~Me)2CH2O
4-OCF3 4-F 4-CN thu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 4-Cl H iPr S OEt OEt 4-C1 4-Cl H iPr S OEt OEt 4-OCF3 4-Cl H ~Pr S OEt OEt 4-CF3 4-F H iPr S OEt OEt 4-OCF3 4-F H iPr S OEt OEt 2~n~6s Rl R2 R3 R~ yl YlRlo YlR
4-OCF2H H iPr S OEt OEt 4-OCF3 4-OCF2H H iPr S OEt OEt 4-CE3 4-Pr H iPr S OEt OEt 4-CF3 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt 10 4-CF3 4-F 4-Cl iPr S OEt OEt 4-OCF3 4-F 4-Cl lPr S OEt OEt 4-CF3 4-OCF2H 4-Cl iPr S OEt OEt 4-OCF3 4-OCF2H 4-CI iPr S OEt OEt 9-CF3 4-C1 4-CN iPr S OEt OEt 15 4-OCF3 4-C1 4-CN iPr S OEt OEt 4-CF3 4-F 4-CN iPr S OEt OEt 4-OCF3 4-F 4-CN iPr S OEt OEt 4-CF3 4-C1 4-CO2Me iPr S OEt OEt 4-CF3 4-Cl H iPr S OCH2C(Me)2CH2O
20 4-OCF3 4-Cl H iPr S OCH2C(Me)2CH2O
4-CF3 4-F H iPr S OCH2C(Me)2CH2O
4-OCF3 4-F H iPr S OCH2C(Me)2CH2O
;
:. .,: ' , - ' : '' ' ' : : :
2~1~Q~65 4-CF3 4-OCF2H H iPr S OCH2C(Me)2CH20 4-CF3 4-Br H lPr S OCH2C(Me)2CH20 4-CF 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-C1 4:C1 4-Cl ;Pr S OCH2C(Me)2CH20 4-Br 4-C1 4-Cl iPr S OCH2C(Me)2CH20 `G
4-OCF3 4-C1 4-Cl ~Pr S OCH2C(Me)2CH20 4-OCF2H 4-C1 4-Cl lPr S OCH2C(Me)2CH20 4-CF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-9r 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-OCF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-CF3 4-OCF2H 4-Cl iPr S OCH2C(Me)2CH20 4-OCF3 2 iPr S OCH2C(Me)2CH20 4-CF3 4-C1 4-CN iPr S OCH2C(Me)2CH20 4-OCF3 4-C1 4-CN iPr S OCH C~Me) CH O
4-CF3 4-F 4-CN iPr S OCN2C(Me)2CH20 4-OCF3 4-F 4-CN iPr S OCH2C(Me)2CH20 4-CF3 4-C1 4-CO2Me iPr S ocH2c(Me) 4-CF3 4-Cl H tBu S OiPr OiPr .
4-CF3 4-F H tBu S OiPr OiPr 4-CF3 4-OCF2H H tBu S OCH2CH2CH20 4-OCF3 4-OCF2H H tBu S OCH2CH2CH20 ...
4-CF3 4-Br H t8u S OCH2CH2CH20 4-CF3 4-C1 4-Cl tBu S OCH2CH20 4-Br 4-C1 4-Cl tBu S OCH2CH20 4-OCF3 4-C1 4-Cl tBu S OCH2CH20 4-CF3 4-F 4-Cl Me S OEt OEt 4-OCF3 4-F 4-Cl ~e S OEt OEt . , 4-CF 4-OCF2H 4-Cl . Me S OEt OEt 4-C1 4-OCF2H 4-Cl Me S OEt OEt 4-CF3 4-F 4-CN tBu O O~t OEt 4-OCF3 4-F 4-CN t~u O OEt OEt 4-CF3 4-C1 4-CO2Me tBu O OCH2C~Me)2CH20 :
- : : ,: . - : : , . :
" . . ~ ;:: .
- : .. :: :: .
lable 19 R2 ~ ~ R3 N ~
O~yl ~
S 11 ~ .
~ -P-Y R,1 R~ Rlo .:
:
Rl R2 R3 R8 yl R1o YlRll R:
4-CF3 4-Cl N iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt 4-CF3 4-F H iPr O Et OEt 4-OCF3 4-F H iPr O Et OEt 4-CF3 4-OCF2~ H iPr O Et OEt 4-OCF 4-OCF H H iPr O Et OEt 4-CF3 4-Br H iPr O Et OEt 4-CF3 4-C1 4-Cl iPr O Et OEt 4-C1 4-C1 4-Cl iPr O Et OEt 4-Br 4-C1 4-C1 iPr O Et OEt 4-OCF3 4-C1 4-Cl iPr O Et OEt 4-OCF2H 4-C1 4-Cl iPr O Et OEt 4-CF3 4-F 4-Cl iPr O Et OEt 4-C1 4-F 4-Cl lPr O Et OEt 4-~r 4-F 4-Cl iPr O Ee OEt L6s 157 :
1 ~2 R3 R8 yl Rlo ylR
i-oCF3 4-F 4-Cl iPr O Et OEt 4-CF3 4-OCF2H 4-Cl iPr O ~t OEt 4-OCF3 4-OCF2H 4-Cl iPr O Et OEt 4-CF3 4-C1 4-CN iPr O Et OEt 4-OCF3 4-C1 4-CN iPr O Et OEt 4-C~3 4-F 4-CN iPr O Et OEt 4-OCF3 4-F 4-CN iPr O Et OEt 4-CF3 4-C1 4-CO2Me iPr O Et OEt 4-CF3 4-Cl H iPr O Et OiPr :. .
4-OCF3 4-Cl H iPr O Et OiPr 4-CF3 4-F H iPr O Et OiPr 4-OCF3 4-F H iPr O Et OiPr ~:
4-CF3 4-OCF2H H iPr O Et OiPr 4-OCF3 4-OCF2H H iPr O Et OPh 4-OCF2H 4-OCF2H H iPr O ~t OPh ::
3,4-CH2C(Me)2O 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh ;
4-CF3 4-C1 4-Cl iPr O Et OPh 4-C1 4-C1 4-Cl iPr O Et OPh :.
4-Br 4-C1 4-Cl lPr O Et OPh 4-OCF3 4-C1 4-Cl iPr O Et OPh 4-OCF2H 4-C1 4-Cl iPr O Et OPh . .
4-CF3 4-F 4-CN tBu O Et OEt 4-OCF3 4-F 4-CN tBu O Et OEt 4-CF3 4-C1 4-CO2Me t8u O Et OEt ~, 9-CF3 4-Cl H tBu O Et OiPr 4-OCF3 4-Cl H tBu O Et OiPr 4-C~3 4-F H tBu O Et OiPr 4-OCF3 4-F H tBu O Et OiPr . .
4-CF3 4-OCF2H H tBu O Et OiPr 4-OCF3 4-OCF2H H Ph O Et OEt :. .. , ~: , .: :. . : , . : , :
:, . . ..
Z~ 6~
R1 R2 R3 R~ yl ~ YlR
i-CF3 4-F H ~Pr S Et OEt 4-OCF3 4-F H iPr S Ph OEt 4-CF3 4-OCF2H 4-Cl tBu S Et OEt 4-OCF3 4-OCF2H 4-Cl tBu S Ph OEt 4-CF3 4-F 4-CN iPr S iPr OiPr 4-OCF3 4-F 4-CN iPr S nPr OEt 4-CF3 4-C1 4-CO2Me tBu S Me OEt ~`
2~Q~L65 159 :
Table ~0 Rz ~ 3 ~ ~ R~
S ~
R9 :, Rl ' R2 R3 Rg 4-CF3 4-Cl H CF3 :
4-CF3 4-F 3 ~;
4-CF3 4-OCF2H 3 ;
4-CF3 4-Br 3 4-C1 4-C14-Cl CF
3~ 4-Br 4-C14-C1 3 3~4-cH2c~Me)2o 4-C1 4-ClCF3 Q~65 160 :~
4-CF 4-F 4,-CN 3 4-CF3 4-Cl q-COzMe CF3 4-CF3 4-C1 M 0-6ecBu 4-CF3 4-F M 0-6ecBu -CF3 4-OCF2H M 0-6ecBu 4-C1 4-OCF2H N 0-6ec8u 4-OCF3 4-OCF2H H 0-6ecBu 4-CF3 4-9r M 0-6ecBu 4-CF3 4-C1 ~I-C1 0-6ecBu 4-C1 4-C1 4-C1 0-6ecBu 4-Br 4-C1 4-C1 O-secBu 4-OCF3 4-C1 4-C1 0-8ecBu 4-CF3 4-F 4-C1 0-6ecBu 4-C1 4-F 4-C1 0-6ecBu 4-OCF3 4-F 4-C1 O-secBu 4-CF3 4-OCF2H 4-C1 0-6ecBu 4-OCF3 4-OCF2H 4-Cl O-~ecBu 4-CF3 4-C1 4-CN 0-6ecBu i~
4-CF3 4-F 4-CN 0-6ecBu ..
4-CF3 4-C1 4-C02Me O-sec8u 4-CF3 4-Cl H O-n-Bu 4-CF3 4-F H O-n-Bu 4-CF3 4-OCF2H H O-n-Bu 4-C1 4-OCF2H H O-n-Bu 4-Br 4-OCF2N H O-n-Bu 4-OCF3 4-OCF2H H O-n-Bu 4-OCF2~ 4-OCF2N H O-n-8u 3~4-cH2c(Me)2o 4-OCF2H H 9-n-Bu 4-CF3 4-Br H O-n-Bu 4-CF3 4-C1 4-Cl O-n-9u 4-C1 4-C1 4-CI O-n-Bu 4-OCF3 4-C1 4-Cl O-n-9u 4-CF3 4-F 4-Cl O-n-hexyl . : ~,-: , ,:: - , : . - ,-. : . : :. ., , - : . . :
. : : . . , , : . ~.:: . .. , . :. , . ::: .: :
- ~ . , : . . , , :~ : . ,: : :. .. ,: .. . . ... .
.. . . .
r~ .
Rl R2 R3 Rg 4-C1 4-F 4-Cl O-n-hexyl 4-OCF3 4-F 4-Cl O-n-hexyl 4-CF3 4-OCF2H 4-Cl O-n-hexyl 4-CF3 4-C1 4-CN. O-n-hexyl 4-CF3 4-F 4-CN O-~-hexyl 4-CF3 4-C1 4-CO2Me O-~-hexyl :
4-CF3 4-OCF2H B CH2ccl3 4-CF3 4-Br H OCH2~C13 :
4-CF3 4-C1 4-Cl OCB2CC13 4-C1 4-C1 4-Cl OCH2CC1 4-OCF3 4-C1 4-Cl OCH2CC13 4-CF3 g-F 4-Cl OCH2CH2OEt 4-CF3 4-OCF2H 4-Cl OCH2CH2OEt 4-CF3 4-C1 4-CN OCH2CH2OEt 4-CF3 4-F 4-CN OCH2CH2OEt q_CF3 4-C1 4-CO2Me OCH2CH2OEt . :~
`~'.
. .
'.' ', '' ',-,': ' ' ," ~ ' .,' '. . -'. ' " `:
' . : ' ' .'., .' . . :. '', . .' , , , .:
6~;
~able 21 R2 ~ R3 }
S -P-1~Rlc ORl, Rl R2 R3 Rlo R
4-CF3 4-Cl H Et Et 3 H Et Et 4-CF3 4-OCF2H H Et Et 4-CF3 4-Br H Et Et 4-CF3 4-C1 4-Cl Et Et 4-Cl . 4-C1 4-Cl Et Et 4-Br 4-C1 4-Cl Et Et 4-OCF3 4-C1 4-Cl Et Et 4-OCF2H 4-C1 4-Cl Et Et 3,4-CH2C(Me)2O 4-C1 4-Cl Et Et 4-CF3 g-F 4-Cl Et St 4-C1 4-F 4-Cl ~t ~t 4-Br 4-F 4-Cl Et Et ,1'.~. ."::
.: - . - . , . ., - , . . .- . .. ; , -.. .. . .. ...... . .. . .... .. .. ...... .. .. . ....
- . ,; , : . , . : . . : .. . . . .
2~ 65 Rl R2 R3 Rlo Rll 4-OCF3 4-F 4-Cl Et Et 4-OCF2H 4-F 4-Cl Et Et 3,4-CH2C(Me)20 4-F 4-Cl Et Et 4-CF3 4-OCF2B 4-Cl Et Et 4-CF3 4-C1 4-CN Et Et 4-CF3 4-F 4-CN Et Et 4-CF3 4-C1 4-CO2Me Et Et 4-CF3 4-9r 2 2 4-CF3 4-C1 4-Cl-CHZcH2-4-C1 4-C1 4-Cl-CH2CH2-4-OCF3 4-C1 4-Cl-CH2CH2-4-C1 4-OCF2H 4-Cl-CH2CH2CH2- .
4-OCF3 4-OCF2H 4-Cl-CH2CH2CH2- ' 4-CF3 .4-F 4-CN-CH2CH2CH2-4-CF3 4-C1 4-CO2Me2 2 2 4-CF3 4-Cl H-CH2C(Me)2CH2-4-CF3 4-F H-cH2cSMe)2~H2-4-CF3 4-OCF2H H-CH2C(Me)2CH2-. ..
4-CF3 4-Br H-CH2C(Me)2CH2-q-CF3 4-C1 4-Cl-CH2C(Me)2CH2-4-C1 4-C1 4-Cl-CH2C(Me)2CH2-4-9r 4-C1 4-Cl-CH2C(Me~2CH2-4-OCF 4-C1 4-Cl-CH2C(Me)2CH2-: - . ~ . . . . ................ .
.
6~;
Rl R2 R3 Rlo Rll 4-OCF2H 4-C1 4-Cl -CH2C(Me)2CH2-3,4-CH2C~Me)2O 4-C1 4-Cl -CH2C~Me32CH2-4-CF3 4-F 4-Cl Ph Ph 4-CF3 4-OCF2H 4-Cl Ph Ph 4-CF3 9-C1 4-CN Ph Ph 4-CF3 4-F 4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph ;.
~ .
~lOQ~65 Table 22 R,~3 ~N ,~R1 "' S
~N--R"
Rl R2' R3 R8 R12 .
4-CF3 4-Cl H nBu nBu 4-C1 4-Cl H ni3u nBu 4-OCF3 4-Cl H nBu nBu 4-CF3 4-F H nBu nBu 4-CF3 4-OCF2H H nBu nBu 4-OCF3 4-OCF2H H nBu nBu 4-CF3 4-Br H nBu nBu ~ .
4-CF3 4-C1 4-Cl nBu nBu 4-C1 4-C1 4-Cl DBu DBu 4-Br 4-C1 4-Cl nBu nBu 4-OCF3 4-C1 4-Cl DBu nBu . .
4-CF3 4-F 4-Cl-CH2CH2CH2CB2CH2-~ !
2C~3Q165 R~ R2 R3 R8 R12 4-CF3 4-C1 4-CO2Me -CH2CH2CH2CH2CH2-4-CF3 4-Cl H -CH2cH2cH2cH2-4-CF3 4-F H -CH2cH2cH2cH2-4-OCF3 4-F H -CH2cH2cH2cH2-4-OCF3 4-OCF2H H -CH2cH2cH2cH2-4-CF3 4-Br H -CH2cH2cH2cH2-4-CF3 4-C1 4-Cl -CH2CH20CH2CH2-4-C1 4-C1 4-Cl -CH2CH20CH2CH~-4-Br 4-C1 4-Cl -CH2CH20CH2CH2-4-OCF3 4-C1 4-Cl -CH2CH20CH2CH2-4-CF3 4-F 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-OCF2H 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CN -CH2CHMeOCHMeCH2- : .
4-CF3 4-F 4-CN -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CO2Me -CH2CHMeOCHMeCH2_ 4-CF3 4-Cl H Et c 4-CF3 4-F H Et c 4-CF3 4-OCF2H H Et cyclo-c6 4-CF3 4-~r H Et cyClo-c6 4-CF3 4-C1 4-Cl Et Cyclo-c6 4-C1 4-C1 4-Cl Et c 4-Br 4-C1 4-Cl Et c 4-OCF3 4-C1 4-Cl Et c 4-CF3 4-F 4-Cl iPr -CH2CH2CO2E~
4-C1 4-F 4-Cl iPr -CH2CH2CO2ET :
4-CF3 2 iPr -CH2cH2c2ET
i-Cl 2 C iPr -CH2CH2CO2ET
4-Pr 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-OCF 4-OCF2N 4-Cl iPr -CH2CH2CO2ET
., , . .. ~ , . . ,. . , . , . . .: . ., ., . : . .
2C!0Q~6S
Rl R2 R3 R8 R12 4,OCF2H 4-OCF28 4-Cl iPr 2 2 2 3,4-C82C(Me)2O 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-CF3 4-C1 4-CN iPr -CH2CH2CO2ET
4-C1 4-C1 4-CN iPr -CH2cH2c2ET
4-OCF 4-C1 4-CN ~F3 2,4-~i-Cl-Ph 4-CF3 4-F 4-CN CF3 2,4-di-Cl-Ph 4-CF3 4-C1 2 3 2,4-di-Cl-Ph -~0 : -.. , , . .. . ., , ~, , . :.
-: ", , . - . ~
;~lOQ16S
~z ~ ~ R3 ~ ~Rl S--SRlo .
Rl R2 R3 R10 :~::
4-CF3 4-Cl H tBu -:
4-OC~ 4-Cl H tBu 4-CF3 4-F H tBu 4-CF3 4-OCF2H H tBu 4-OCF3 4-OCF2H H tBu 4-CF3 4-Br H tBu 4-CF3 4-C1 4-Cl tBu 4-C1 4-C1 4-Cl tBu 4-Br 4-C1 4-Cl tBu 4-OCF3 4-C1 4-Cl tBu :.:-4-OCF2H 4-C1 4-Cl tBu .
4-C~3 4-F 4-Cl tBu ~ s 4-CF3 4-OCF2H 4-Cl tBu ~ .-'.
.. ' !, . ' , . -, . ' , . . ' , ' ' : . : . ': ,. .: , ' : . ', .' :' ' ., .
..' . ''.' ' " , ' ' . ' . " ' " ,. .' . .' ; ' ," ' '., . - .' ' : "." . ', ' ' .' ' ' ' ' :' .'. '.., ,.',', ' . :-" ' . ' ' '~. ' : ' ' ~)Q~65 Rl R2 R3 R~o i-Cl 4-OCF2H 4-Cl tBu 4-OCF3 4-OCF2H 4-Cl tBu 4-CF3 4-C1 4-CN tBu 4-CF3 4-F 4-CN tBu -CF3 4-C1 4-CO2Me tBu 4-CF3 4-Cl H sec-Bu 4-OCF3 4-Cl H 6ec-Bu .
4-CF3 4-F H 6ec-Bu 4-OCF3 4-F H ~ec-Bu 4-CF3 4-OCF2H H 6ec-Bu 4-C1 4-OCF2H H sec-Fu 4-OCF3 4-OCF2H H Ph 4-OCF2H 4-OCF2H H Ph 3,4-CH2C(Me)20 4-OCF2H H Ph 4-CF3 4-Br H Ph 4-CF3 4-C1 4-Cl Ph 4-C1 4-C1 4-Cl Ph 4-Br 4-C1 4-Cl Ph 4-OCF3 4-C1 4-Cl Ph 4-OCF2H 4-C1 4-Cl Ph 3,4-CH2C(Me)20 4-Cl 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ,, .
4-Br 4-F 4-C1 4-Cl-Ph 4-OCF3 4-F 4-C1 4-Cl-Ph 4-OCF2H 4-F 4-C1 4-Cl-Ph 3~4-CN2C(Me)20 4-F 4-C1 4-Cl-Ph 4-CF3 4-OCF2H 4-C1 4-Cl-Ph 4-CF3 4-C1 4-CN 4-Cl-Ph 4-OCF3 4-C1 4-CN 2-Me-4-t-Bu-Ph , . .. - ., ., . . ., , :, . ~: :. .
2~!0Q~6S
Rl R2 R3 Rlo .
4-CF 4-F 4-CN2-Me-4-t-Bu-Ph 4-OCF3 4-F 4-CN2-Me-4 t-Pu-Ph 4-CF3 4-C1 4-CO2Me2-Me-4-t-Bu-Ph 4-CF3 4-C1 ~ 2-NO2-Ph 4-OCF3 4-Cl H 2-NO2-Ph 4-CF3 4-F H 2-NO2-Ph 4-OCF3 4-OCF2H H 2-NO2-Ph 4-CF3 4-Br H 2-NOz-Ph 4-CF3 4-C1 4-C1 2-NO2-Ph 4-C1 4-C1 4-C1 2-NO2-Ph 4 Br 4-C1 4-C1 2-NO2-Ph 4-Cl 9-F 4-C1 2-NO2Ph 4-OCF3 4-F 4-C1 2-NO2Ph 4-CF3 4-OCF2H 4-C1 2-NO2Ph 4-OCF3 4-OCF2H 4-C1 2-NO2Ph . .
4-CF3 4-C1 4-CN 2-NO2Ph 4-OCF3 4-C1 4-CN 2-NO2Ph 9-CF3 4-F 4-CN 2-NO2Ph 4-CF3 4-C1 4-CO2Me2-NO2Ph ~ ' ~
~ ~ :
. .. ~ , . . - , ; i .
~ 0~65 Table 24 0 ~ 3 Ra fi--N
O
Rl R2 R3 Z
4-CF3 4-H 4-Cl CH3 4-CF3 4-H 4-F C~3 4-CF3 4-F 4-Cl CH3 4-CF3 . 4-C1 4-H CH3 ~0 ' 4-C1 4-Cl CN3 4-CF3 4-C1 4-F C~3 4-CF3 4-OCHF2 4-Cl CH3 ...,. :.~ .~ ., ... . . . , : : ,: . : .
: . . , . , : - , . . . : . :
.: .. ... ' . :.. :: . . . : :: - . -2~ 65 Rl R2 R3 z 4-OCF3 4-B 4-Cl ~H3 4-OCF3 4-F 4-Cl CH3 4-OCF3 4-C1 4-Cl CH3 4-C1 4-H 4-Cl CH
4-C1 4-C1 4-Cl CH3 4-C1 4-F 4-Cl CH3 4-Br 4-H 4-H CH3 4-Br 4-H 4-F CN3 4-Br 4-H 4-Cl CH3 4-Br 4-C1 4-H CH3 4-Br 4-C1 4-F CH3 4-Br 4-C1 4-Cl CH3 4-Br q-F 4-H CH3 4-Br 4-F 4-F CH3 4-Br 4-F 4-Cl CH3 4-OCHF2 4-H 4-H ~H3 4-OCHF2 4-H q-Cl Q3 , '. ';'' , ' :'`'.'. '''' ' " ,`''.' '''' ' ' :''' ' , . . . , . . ~. . .`. ~ . . . .
2~ 6S
Rl ~2 R3 Z
4-OCHF2 4-F 4-Cl CH3 4-OCHF2 4-C1 4-Cl C~3 4-CF3 4-~ 4-Cl CH3C~2 4-CF3 4-F 4-Cl CH3CH2 4-CF3 4-Cl g-Cl CH3CH2 4-CF3 4-OCHF2 4-Cl CH3CN2 4-OCF~ 4-H 4-Cl CH3CH2 4-OCF3 4-F 4~H CH3CH2 4-OCF3 4-F 4-Cl CH3CH2 4-OCF3 4-C1 4-Cl CH3CH2 4-C1 4-H 4-Cl N3CH2 6~;
Rl R2 R3 Z
.
4-C1 4-C1 4-Cl CH3CH2 4-C1 4-C1 4-F CH3CH2 :A
4-C1 4-F 4-H CH3CH2 ~
4-C1 4-F 4-Cl CH3CH2 ~ ~
4-C1 4-F 4-F CH3CH2 : .
4-CF3 4-~ 4-Cl C6H5 i.~;
4-CF3 4-H 4-F C6H5 .
lS 4-CF3 4-F 4-H C6H5 4-CF3 4-F 4-Cl C6H5 4-CF3 4-F 4-F C6H5 :
4-CF3 4-C1 4-Cl C6H5 ~ -4-CF3 4-OCHF2 4-Cl C6H5 . :~.
4-OCF3 4-H 4-H C6H5 .
4-OCF3 4-H 4-Cl C6H5 4-OCF3 4-H 4-F C6H5 , . .
4-OCF3 4-F 4-H C6H5 ..
4-OCF3 4-F 4-Cl C6H5 4-OCF3 4-C1 4-H C6H5 ~:
4-OCF3 4-C1 4-Cl C6H5 ':
4-OCF3 4-C1 4-F C6H5 :
4-C1 4-H 4-Cl C6H5 4-C1 4-H 4-F C6H5 : , .' ' - ,:
2~0~65 ., Rl R2 R3 Z
4-C1 4-F 4-Cl C6H5 g-Cl 4-F 4-F C6H5 4-CF3 4-~ 4-Cl CR3~
4-CF3 4-H 4-F C~30 4-CF3 4-F 4-Cl CH30 4-CF3 4-C1 4-Cl C~30 4-CF3 4-OCHF2 4-Cl CH30 4-OCF3 4-H 4-Cl CH30 g-OCF3 4-F 4-H CH30 4-OCF3 4-F 4-Cl CH30 4-OCF3 4-C1 4-Cl CH30 g-Cl 4-N 4-Cl CH30 4-C1 4-C1 4-Cl CH30 ` ' I
~ 2(1~Q~65 Rl R2 R3 Z
4-C1 4-F 4-Cl CH30 .
4-CF3 4-H 4-Cl 4-CF3 4-F 4-Cl H
4-CF3 4-C1 4-Cl H . :
4-CF3 4-OCNF2 4-H H . :
4-CF3 4-OCHF2 4-Cl . H
4-OCF3 4-H 4-Cl H
4-OCF3 4-H 4-F H :
2~ 4-OCF3 4-F 4-Cl H ;
4-OCF3 4-C1 4-Cl H
4-OCF3 4-C1 4-F H .
4-C1 4-H 4-Cl 4-C1 4-C1 4-Cl H
4-Cl 4-C1 4-F H
.. . - .: ; ` . :~: : ,.
, : , ~ . ... : .. ... . .. . .
:, , : . , , . ~ .
2noQ~6s Rl R2 R3 Z
4-C1 4-F 4-Cl H
4-CF3 4-C1 4-Cl BrCH2 4-CF3 4-C1 4-Cl ClCH2 4-CF3 4-C1 4-Cl CF3 4-CF3 4-C1 4-Cl benzyl 4-CF3 4-C1 4-Cl CH3CH2CH2 4-CF3 4-C1 4-Cl CH3(CH2)3 4-CF3 4-C1 4-Cl CH3(CH2)4 4-CF3 4-C1 4-Cl CH3(CH2)5 4-CF3 4-C1 4-Cl CH3(CH2)6 4-CF3 4-C1 4-Cl CH3(CH2)7 4-CF3 4-C1 4-Cl CH3(CH2)9 , 4-CF3 4-C1 4-Cl CH3(CH2)lo 4-CF3 4-C1 4-Cl C13C
9-CF3 4-C1 4-Cl i-P~
4-CF3 4-C1 4-Cl t-Bu 4-CF3 4-C1 4-Cl MeO2C
4-CF3 4-C1 4-Cl EtO2C
4-CF3 4-C1 4-C1 2-Cl-phenyl 4-CF3 4-C1 4-C1 3-Cl-phenyl 4-CF3 4-C1 4-C1 4-Cl-phenyl ~:;
4 CF3 4-C1 4-Cl CH3CH20 4-CF3 4-C1 4-Cl CH3(CH2)20 4-CF3 4-C1 4-Cl CH3~CH2)40 4-CF3 4-C1 4-Cl CH3(CH2)~0 4-CF3 4-C1 4-Cl CH3(CH2)80 4-CF3 4-C1 4-Cl CH3(CH2)100 4-CF3 4-C1 4-Cl phenyl-0 4-CF3 4-C1 4-C1 4-Cl-phenyl-0 .: . : . :" - . :: ' `:: ~ ' : . .: :: , :
2(10(~6S
. , Rl R2 R3 Z
5 . .
4-CF3 4-C1 4-Cl benzyl-O
4-C1 4-C1 4-Cl ClCH2 4 -C1 4 -Cl 4-Cl CF3 4-C1 4-C1 4-Cl benzyl 4-C1 4-C1 4-C1 3(CH2)3 4-C1 4-C1 4-Cl CH32C
4-C1 4-C1 4-Cl CH3CH2O .
- 2 5 ~ ~ :
:, ';
~, ;. . : .. :. :. . . ,.. : . . .
2(1QtQ~65 Table 25 ~ ~ R3 ;
N ~ .
R~ .
O
Nl ~ 9 Rl ~2 R3 R8 Rg , 4-CF3 4-Cl H Me O-nBu 4-OCF3 4-Cl H Me O-~Bu 4-CF3 4-F H Me O-nBu 4-OCF3 4-F H Me O-nBu 4-CF3 4-OCF2H H. Me O-nBu 4-CF3 4-Br H Me O-nBu 4-CF3 4-C1 4-ClMe O-nBu 4-C1 4-C1 4-ClMe O-nBu 4-Br 4-C1 4-Cl.~e O-nBu 4-OCF3 4-C14-Cl Me O-nBu 4-CF3 4-F 4-ClMe O-nBu 4-CF3 4-OCF2H 4-ClMe O-nBu 4-CF3 4-C1 4-CNMe O-nBu ~5 -. . . : . . . . .. : : - . , : : : :
: : : . ,: : : , .: . . . . . : . : . .
, . .. . .. . ,. ,:
0~65 , 180 ~
, . .
Rl R2 R3 R8 Rg ...
,. ~
4-CF 4-F 4-CN Me O-nBu 4-CF3 4-C1 4-C02Me Me O-nBu 4-CF3 4-Cl H Me O-n-he~yl 4-CF3 4-F H Me O-n-he~yl 4-CF3 4-OCF2H B Me O-D_OCtY1 4-CF3 4-Br ~ Me O-n-dccyl 4-CF3 4-C1 4-Cl Me O-n-dodecyl 4-C1 4-C1 4-Cl Me O-n-dodecyl 4-Br 4-C1 4-Cl Me O-n-dodecyl 4-OCF3 4-C1 4-Cl Me O-n-dodecyl 4-CF3 4-F 4-Cl Me 0-6ec-Bu :~
4-C1 4-F 4-Cl Me O-~ec-Bu 4-Br 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me 0-6ec-Bu 4-CF3 4-OCF2H 4-Cl Me 0-6ec-Bu 4-CF3 4-C1 4-CN Me O-iPr :;
4-CF3 4-F 4-CN Me oCH2CH20Et ~.
4-CF3 4-C1 4-C02Me Me OCHz~F3 4-CF3 4-Cl H Me F .:~
4-CF3 4-F H Me 2 4-CF3 4-OCF2H H Me NEt2 4-CF3 4-Br H Me morpholino 4-OCF3 4-Br H Me n-Pr 4-CF3 4-C1 4-Cl Me cec-Bu 4-Br 4-C1 4-Cl Me Ph 4-OCF3 4-C1 4-Cl Me Ph 4-CF3 4 r 4-Cl Et O-iPr -~
4-CF 4-OCF2H 4-Cl Et O-iPr ~;
4-CF3 4-C1 4-CN Et C~2CC13 4-OCF3 4-C1 4-CN Et 2 4-CF3 4-F 4-CN Et 2,6-di-Me-morpholino 4-C1 4-F 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-C1 4-C02Me Et Ph ~~
4-CF3 4-Cl H iPr OEt '~
4-CF3 4-F H iPr OEt ,..:
, . :.' -, , `' ' , ''' ~ ' , ' ' ': ': ~ ' ' . ' ' ' ' ~ ' , ' '. - ' -: ' ' ' ' ' ' ' ' :~ :
~OQ~65 Rl R2 R3 R8 R9 4-CF3 4-OCF2H H iPr OEt 4-C1 4-OCF2H H ~Pr OEt 4-Br 4-OCF2H H iPr OEt 4-OCF3 4-OCF2H H iPr OEt 4-OCF2H 4-OCF2H H iPr OEt 3,4-CH2C(Me)20 4-OCF2H 8 iPr OEt 4-CF3 4-Br H iPr OEt 4-CF3 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt 4-CF3 4-F 4-Cl iPr OEt 4-OCF3 4-F 4-Cl iPr OEt 4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2H 4-Cl iPr OEt 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt 4-CF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt 4-OCF3 4-C1 4-CO2Me iPr OEt 4-CF3 4-OMe 4-Cl iPr OEt 4-C1 4-OPh 4-Cl iPr OEt 4-Br 4-SCF2H 4-Cl iPr OEt 4-OCF3 4-No2 4-Cl iPr OEt 4-OCF2H 4-SMe 4-Cl iPr OEt 3,4-CH2C(Me)20 4-SO2Me 4-Cl iPr OEt 4-CF3 4-CN 4-Cl iPr OEt 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt ~-OCF3 4-Me 4-Cl iPr OEt 4-OCF2H 4-0-allyl 4-Cl iPr OEt 3,4-C~2ClMe)20 4-CF3 4-Cl iPr OEt 4-CF3 4-C1 4-CO2Et ~Pr OEt 4-C1 4-C1 4-OMe iPr OEt 4-Br 4-C1 2 2 t 4-OCF3 4-C1 4-OCF2CF2H iPrOEt .1,~:... ; :
.. . - . . ~....... ,,, . .. : . -.. : .. , :.- .- .. ., , . :.~:. :.
2~Q~6S
Rl R2 R3 Rf~, Rg i-CF3 4-C1 4-CF3 iPr OEt 4-C1 4-C1 4-Me iPr OEt 4-8r 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-Cl g-No2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu 4-CF3 4-F H iPr O-n-Bu ~ :
4-OCF3 4-F H iPr OCH2CO2Me :
4-CF3 4-OCF2~ H iPr NMe2 4-OCF3 4-OCF2H H iPr piperidino 3,4-CH2C(Me)2O 4-OCF2H H iPr Et :
4-CF3 4-Br H iPr Et 4-OCF3 4-Br N CH2Ph OEt 4-CF3 4-C1 4-CO2Me CH2Ph NME2 .
. . ~ . ~ :
. . .
2~Q~65 Table 26 ' 2 ~ ~ 3 R
O
~ -S -R9 R~ O
R1 R2 R3 R8 Rg 4-CF3 4-Cl H Me 2 4-CF3 4-F H Me 2 4-CF3 4-OCF2H H Me n-hesyl 4-OCF3 q-OCF2N H Me Ph 4-CF3 4-Br H Me 4-Me-Ph :
4-CF3 4-C1 4-Cl Et morpholino 4-C1 4-C1 4-Cl Et iPr 4-Br 4-C1 4-Cl Et n-Bu 4-OCF3 4-C1 4-Cl Et Ph 4-CF3 4-F 4-Cl iPr NMe2 4-CF3 2 iPr piperidino 4-C1 2 iPr Et !':`' ' ':
4-8r 4-OCF2H 4-Cl ~Pr n-Bu 4-OCF3 4-OCF2H 4-C1 iPr Ph 4-OCF~H 4-OCF2H 4-Cl iPr 4-Cl-Ph 2~0Q~6~; ;:
~ble 27 R2 ~ ~ R3 P~
~,~1 .
S`N "
--P--Y Rlo R~ Y Rl 1 ~.
Rl R2 R3 R8 yl YlR 0 YlR
4-CF3 4-Cl H tBu S OEt OEt 4-C1 4-Cl H tBu S OEt OEt 4-Br 4-Cl N tBu S OEt OEt 4-OCF3 4-Cl H tBu S OEt OEt 4-OCF2H 4-Cl H tBu S OEt OEt 3~4-cH2c(Me)2o 4-Cl H t8u S OEt OEt 4-CF3 4-F H tBu S OEt OEt 4-C1 4-F H tBu S OEt OEt 4-Br 4-F H tfiu S OEt OEt 4-OCF 4-F H tBu S OCH2C(Me)2CH20 4-OCF2H 4-F H tBu S OCH2C(Me)2CH20 .
3~4-cH2c(Me)2o 4-F H tBu S OCH2C(Me)2CH20 4-CF3 4-OCF2H H tBu S OCH2C(Me~2CH20 4-C1 4-OCF2H H tBu S OCH2c(Me)2cH20-4-Br 4-OCF2H H t8u S OCH2C(Me)2CH20 ," , .
. .
.,., . ~ ~: : , ti~"' S ~,~
Rl R2 R3 RB yl YlR YlR
S ..
4-OCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-OCF2H 4-OCF2H H tBu S OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-OCF2H H tBu 5 OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-C1 4-Br H iPr S OFt OEt 4-Br 4-Br H iPr S OEt OEt 4-OCF3 4-Br H iPr S OEt OEt 4-OCF2H 4-Br H lPr S OEt OEt 3~4-cH2c(Me)2o 4-Br H iPr S OEt OEt 4-CF 4-C1 4-Cl iPr S OEt OEt 4-C1 4-C1 4-Cl iPr S OEt OEt 4-Br 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt :
4-OCF2H 4-C1 4-Cl iPr S OEt OEt 3,4-CH2C(Me)2O 4-C1 4-Cl iPr S OEt OEt 4-CF3 4-F 4-Cl iPr SOCH2C(Me)2CH2O
4-C1 4-F 4-Cl iPr SOCH2c(Me)2cH2O .
4-Br 4-F 4-Cl iPr SOCH2C(Me)2CH2O .
4-OCF3 4-F 4-Cl iPr SOCH2C(Me)2CH2O
4-OCF2H 4-F 4-Cl iPr SOCH2C(Me)2CH2O
3~4-cH2c(Me)2o 4-F 4-Cl iPr S . OCH2C(Me)2CH2O !;`
4-CF3 2 tBu S OiPr OiPr 4-C1 4-OCF2H 4-Cl tBu S OiPr OiPr 4-Br 4-OCF2N q-Cl t8u S OiPr OiPr 4-OCF3 4-OCF2H 4-Cl t~u S OiPr OiPr 4-OC~2H 4-OCF2H 4-Cl tBu. S OiPr OiPr 2 ~ )2 2 tBu S OiPr OiPr .
4-CF3 4-C1 4-CN tBu S OCH2CH2CH2O
4-C1 4-C1 4-CN tBu S OCH2CH2CN20 4-Br 4-C1 4-CN tBu 2 2 2 :
4-OCF3 4-C1 4-CN tBu S OCH2CH2CH2O
21~0~6S
Rl R2 R3 ~8 yl YlR YlRll 4-OCF2H 4-C1 4-CN tBu S OCH2cN2cH2O ~.
- 3~4-cH2c~Me)2o 4-C1 4-CN tBu S C~2cH2 4-CF3 4-F 4-CN tBu S CH2cH2 4-C1 4-F 4-CN t~u 2 2 4-Br 4-F 4-CN tBu 2 2 4-OCF3 4-F 4-CN Me S OEt OEt 4-OCF2H 4-F 4-CN Me S OEt OEt 3~4-cH2c(Me)2o 4-F 4-C~ Me S OEt OEt 4-Br q-Cl 4-CO2Me tBu O OEt OEt 4-OCF3 4-C1 4-CO2Me tBu O OEt OEt 4-OCF2H 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
':
.,, . . , . . ;-.. ..
: .,. ::: . . .
- : . :'. ~,, :
- , . .
2(loQl6s ~b~
5, .
l0R2 ~ ~ 3 , ~ .
~"~R1 l5~ -P-YlR
R~ R1O
: ':
R1 R2 R3 R8 yl Rlo Y R
-- !
4-CF3 4-Cl H iPr O Et OEt 4-C1 4-Cl H iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt 4-CF3 4-F H iPr O Et O-iPr 4-OCF 4-F H iPr O Et O-iPr .
4-CF3 4-OCF2H H iPr O Et O-iPr 4-OCF3 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh 4-CF 4-Cl 4-Cl iPr O Ph OEt 4-Cl 4-Cl 4-Cl iPr O Ph OEt 4-Br 4-Cl 4-Cl iPr O Ph OEt 4-OC~3 4-Cl 4-Cl iPr O Ph OEt 4-CF3 4-F 4-Cl tBu O Et OEt 4-OCF3 4-F 4-Cl tB~ o Et OEt .
"`' ''. .
OQ~65 Rl R2 R3 RB yl ~10 YlRll .
4-CF3 4-OCF2~ 4-Cl t8u o Et O-iPr 4-OCF3 4-OCF2H 4-Cl t8~ O St O-iPr 4-CF3 4-C1 4-CN Ph O Et OEt q-OCF3 4-C1 4-CN Ph O Et OEt 4-CF3 4-F 4-CN iPr S Ph O-iPr 4-OCF3 4-F 4-CN tBu S Et OEt ;: :
:~!
OQ~6S
189 ::
Table 29 R2 ~ /~3 - !
N~
~ ~ R~
S`GP
R~ :
Rl ~ R2 R3 Rg 4-OCF3 4-F H O-cec-Bu 4-CF3 4-OCF2~ H 0-6ec-Bu . : .
4-Br 4-OCF2H H 0-6ec-9u 4-OCF3 4-OCF2H H 0-6ec-Bu 4-CF3 4-Br H O-n-Bu 4-CF3 4-C1 4-Cl O-D-Bu 4-C1 4-C1 4-Cl O-n-Bu 4-Br 4-C1 4-Cl O-n-Bu 4-OCF3 4-C1 4-Cl O-n-Bu i , ~, 4-CF3 4-F 4-Cl O-n-hexyl ,~
4-CF3 4-OCF2H 4-Cl O-D-hexyl ~-4-OCF3 4-OCF2H 4-Cl O-n-h~xyl ,.
: - , : - . . .,:. . , . - : . : : . : . - : . :, . . . - - j QQ~6S
Rl R2 R3 Rg .
4-OCF3 4-C1 4-CN ~CH2CC13 4-CF3 f.-F 4-CN OCH2CC13 4-CF3 4-C1 4-CO2Me 2 2 ~;, , -., , . .. . ... , ,, . :
. '. ` : .. ' : ': .: : . ' : : . . ::: .. :: . : , : . : . . ' ' ~l :
Z~OQ~65 ~le 30 ~ ~ R
I O
S
OR
Rl ~2 R3 R10 R~
4-CF3 4-Cl H Et Et 4-CF3 4-F H Et Et `~
4-CF3 4-OCF2H H Et Et ~ :~
4-CF3 4-Br H -CH2CH2- ~
4-CF3 4-C1 4-Cl -CH2CH2- ;.
4-Cl 4-Cl 4-Cl 2 2 4-OCF3 4-Cl 4-Cl -CH2CH2-4-CF3 4-F 4-Cl -CH2C~2CH2-4-OCF3 4-F 4-Cl 2 2 2 .
4-CF3 4-OCF2H 4-Cl -CH2CH2CH2-4-OCF3 4-OCF2H 4-CI ,, ' .' '', :~".', .' '.
. , . , . ' ' .: . ~ :.. :. , '' . .; ,~ ' ~, :, ;' .
2(:~0Q~L65 Rl R2 %3 ~10 ~11 4.CF3 4-Cl 4-CN 2 ~ )2 2 4-C~CF3 4-C1 4-CN -CH2C(Me)2CH2-4-CF3 4-F 4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph .: , . . ~ ~ ~ . , : ,: . . :, : :
: :, . . . , : .
- : . . : ::
2(,~65 193 .
Table 31 R2 ~ ~ 3 N ~
~ t Rl R2 R3 R8 R12 :. .
4-C~ 4-Cl H nBu nBu :
4-CF3 4-F H nBu nBu 4-CF3 4-OCF2H H nBu nBu 4-CF3 4-Br 2 2 2 2 2 4-CF3 4-C1 4-Cl -CH2CH20CH2CH2-4-C1 4-C1 4-Cl -CH2CH20CH2CH2-4-OCF3 4-C1 4-Cl -CH2cH2cH2cH2- ::
4-CF 4-F 4-Cl -CH2CH~Me)OCH(Me)CH - , .
4-OCF3 4-F 4-Cl -CH2CH(Me)OCH(Me)CH - ,' 4-CF3 2 Et c 4-OCF3 4-OCF2H 4-Cl Et cycl-C6Hll ' 4-CF3 4-C1 4-CN Et cyclo C6Hll , 4-CF3 4-F 4-~N lPr -CH2cH2c2Et 4-CF3 4-C1 4-CO2Me CF3 2,4-~i-Cl-Ph .: ,., ." ., . ,. , ,, ; , : ,. . ,. :: :, , . ~ . . : . ~, . , 2~0Q~65 ~ble 32 5 . .
1~ ~ N ~ R3 ~,,~R
S
~ R~
Rl R2 R3 R10 4-CF3 4-Cl H tBu 4-CF3 4-F H tBu 4-CF3 4-OCF2H H sec-Bu 4-OCF3 4-OCF2H H sec-Bu 4-CF3 4-Br H 6ec-Bu 4-CF3 4-C1 4-Cl Ph 4-C1 4-C~ 4-Cl Ph 4-OCF3 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ;
4-OCF3 4-F 4-C1 4-Cl-Ph 4-CF3 4-OCF2H 4-C1 4~Cl-Ph 4-OCF3 4-OCF2H 4-C1 2-Me-4-t-Bu-Ph 2~ 6S
Rl R2 R3 Rlo , .
i--CF3 4-C1 4-CN 2-Me-4-t-Fu-Ph 4-CF3 4-F 4-CN 2-NO2-Ph 4-CF3 4-C1 4-CO2Me 2-NO2-Ph '.':' '.
. ~'~
3C . , .
:', .
3S ::
2(10Q~6S
Formulation and Use The compounds of this invention will generally be used in formulation with a carrier comprising a liguid or solid diluent or an organic solvent.
Useful formulations of the compounds of this invention are prepared in conventional ways. They include dusts, baits, traps, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of thes can be applied directly.
Sprayable formulations can be e2tended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99% solid or liquid diluent(s).
More specifically, they will contain these 20 ingredients in the following approximate proportions: -Percent by Weipht Active Inaredient Diluent(s~ Surfactant(s) 25 Wettable Pawders 25-90 0-74 0-10 Oil Suspensions, 1-50 40-95 0-35 Emulsions, Solutions (including Emulsifi-able Concentrates) Dusts 1-25 70-99 0-5 Granules, Baits 0.01-95 5-99 0-15 and Pellets High Strength 90-99 0-10 0-2 Compositions 35Lower or higher levels of active ingredient can, of course, be present depending on the intended : . - . . . . - . . .:
. ~ .: , ~ .:
-... .- . ...
- - - - . : . .
, - , : - ,: , : : . .
- - : :
- : . : . :. . : .
2~Q~6~
use and the physical pr~perties of the compound.
Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mi~ing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers, n 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, ~Solvents Guide,~ 2nd Ed., Interscience, New York, 1950. Solubility under 0.1%
is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at O~C. ~McCurcheon~s Detergents and .' Emulsifiers Annual,~ Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, ~Encyclopedia 20 of Surface Active Agents," Chemical Publ. Co., Inc., '~
New York, 1964, list ~urfactants and recommended uses.
All formulations can contain minor amounts of addi-tives to reduce foam, caking, corrosion, microbiologi-cal growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.
The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, griding as in a hammer or fluid energy mill. Suspensions are prepared by wet-milling (see, for e~ample, U.S. 3,060,0~4). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by a~glomeration techniques. See Browning, "Agglomeration,~ Chemical -.. : . ,. .. : .
:. ~ : ... .. :
Engineerina, December 4, 1967, pages 147 and follow-ing, and ~Perry's Chemical Engineer's Handbook," 4th Ea., McGraw-Hill, New York, 1963, pages 8 to 59 and following.
Many of the compounds of the invention are most efficacious when applied in the form of an emul-sifiable concentrate mixed with a spray oil or spray oil concentrate. Although any oil can be used as a spray oil, spray oils usually have these character-istics: they are not phytoto~ic to the crop sprayed, and they have appropriate viscosity. Petroleum based oils are commonly used for spraying. In some areas, crop oils are preferred such as the following:
Common Crop Oils Used as Spray Oils Corn Oil Linseed Oil Cottonseed Oil Soybean Oil Coconut Oil Sunflower Oil Rapeseed Oil Olive Oil Peanut Oil Palm Oil Safflower Oil Sesame Oil Mustardseed Oil Castor Oil The following oils also meet the criteria for a spray oil: mineral, fish and cod liver oil.
Spray oil concentrates comprise a spray oil together with one or more additional ingredients such as emulsifiers and wetting agents. A number of useful spray oil and spray oil concentrates can be found in "A Guide to Agricultural Spray Adjuvants Used in the United States~ by Thomson, Thomson Publications, California, 1986.
Examples of useful arthropodicidal formulations of compounds of the present invention sre as follows.
:. , - . . :
-. ~ : . . , - ........... -. . : : . - ::
.. . .
Example A
Em~lsifiable Concentrate methyl 4-[3-(4-chlorophenyl)-1-[r(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]- , amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
20%
blend of oil soluble sulfonates and polyo~yethylene ethers 10%
isophorone 70%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filtex is included in packaging operation to insure the substantial absence of e~traneous undissolved material in the product.
Example B
Wettable Powder methyl 4-t3-(4-chloroPhenYl)-l-t[(etho~YcarbonYl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl~benzoate.
30%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 63%
The active ingredient is mixed with the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 5-mesh ~creen.
E~amDle C
Pust methyl 4-t3-(4-chlorophenyl)-1-[[(ethosycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl3-4,5-di-hydro-lH-pyrazol-4-yl3benzoate.
, - - . - . , ., ., , . . . : :
.
,, , .. : . .
s Wettable powder of Example B 10%
pyrophyllite (powder) 90%
s The wettable powder and the pyrophyllite diluent are thoroughly blended and then packeged.
The product is suitable for use as a dust.
Example D
Granule methyl 4-[3-(4-chlorophenyl)-1-t[(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoro-methyl)phenyl]amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate. 10%
attapulgite granules (low volative matter, 0.71/9/30 mm; U.S.S. No.
25-50 sieves) 90~
The active ingredient is dissolved in a vola-tile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven o~ by heating.
The granules are then allowed to cool and are packaged.
Example E
Emulsifiable Concentrate methyl 9-t3-~4-chlorophenyl)~ (ethoxycarbonyl)(l-methylethyl)amino]thio]-N-t9-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
10%
blend of oil soluble sulfonates and polyoxyethylene ethers 4%
isophorone 86%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in packaging operation to insure the ab-sence of any extraneous undissolved material in the product.
' , .
' . . .: - , . , . ., . .. ; . - . ~ . ' ' . ,. ' ' , ~ ,: , : : ,' .:
' . " :'' : . , :: ~ ' ' : , , , .:.-': ,. . ::. ,, ' : ',' ' : , ' , :-; ' .
,,', . -: : ' ~ ~ . .: . . ' , ' . '. .' :'. . ' ' . ~ -: , ' - ' ' .. . ' ; ' . : : . , -: ,' : :., .,. .' ,. -:: ' ' ' . : :
2C!QQ~L65 Example F
Wettable Powder methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
80%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 3%
The active ingredient is blended with the inert materials in a blender. After grinding in a hammermill, the material is reblended an sifted through a U.S.S. 50-mesh screen and packaged.
Example G
Dust wettable powder of E~ample F5%
pyrophyllite (powder) 95%
The wettable powder and the pyrophyllite diluent are thoroughly blended and then packaged.
The product is suitable for use as a dust.
E~am~le H
Granule methyl 4-[3-(4-chlorophenyl)-1-[[(etho~ycarbonyl)(l-methylethyl)amino]thio~-N-[4-(trifluoromethyl)phenyl~-- 30 amino]carbonyll-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
10%
attapulgite granules (low volative matter, 0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90~
The active ingredient is dissolved in a suit-able solvent and sprayed onto dedusted attapulgite granules in a double cone blender. The granules are warmed to drive off solvent, cooled and packaged.
~ , .
,. . : , . . . :: - . .
. , ~ . -, 2~ 6S
~02 Example I
Granule wettable powder of Ex~mple F 15%
gypsum 69~
potassium sulfate 16%
The ingredients are blended in a rotating mixer and water is sprayed on to accomplish granu-lation. When most of the material has reached the desired range of 0.1 to 0.42 mm (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These 15 granules contain 12% active ingredient. ;
Example J
Solution methyl 4-[3-(4-chlorophenyl)-1-[t(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]
amino]carbonyI]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
1~%
4-butyrolactone B5%
The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
ExamDle K
Oil Suspension methyl 4-t3-(4-chloroPhenYl)-l-ll(etho~YcarbonYl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]- .. .
aminolcarbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
20~
sodium alkylnaphthalenesulfonate 4%
sodium ligninsulfonate 4%
low viscosity methyl cellulose 3%
attapulgite 69%
!''1`` ':
" . , ~, , , . . , , , , . . ,, , , :, , ,, , . ,, . ~, , ,~, ...
,: , . : .,. , ~ . ~ , . . . :
:
The active ingredient is blended with the -inert materials in a blender. After grinding in a hammermill to produce particles substantially all below 100 microns, the material is reblended and sifted through a U.S.S. 50-mesh screen and packaged.
Example L
Aaueous Suspension methyl 4-t3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 40%
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ether 0.5%
disodium phosphate 1.0%
monosodium phosphate 0.5%
polyvinyl alcohol 1.0%
water 56.7 The ingredients are blended and ground together in a sand mill to produce particles substantially all under 5 microns in size.
E~ample M
Pil Suspension methyl 4-t3-(4-chlorophenyl)-1-[t(etho~ycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyllamino]carbonyl~-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 35-0%
blend of polyalcohol carbo~ylic 6.0%
esters and oil soluble petroleum sulfonates ~ylene range solvent 59.0%
- , .
: .
. . .
: .. . . .
:. ~ , .. - .: . .. . - ; ~ . -. .
2~ 65 The ingredients are combined and ground tegether in a sand mill to produce particles substantially all below 5 microns. The product can be used directly, e~tended with oils, or emulsified in water.
Example N
Emulsifiable Concent~ate methyl 7-chloro-2-[[N-[[[(he~ylo~y)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 5%
blend of oil soluble sulfonates and polyoxyethylene ethers 4%
~ylene 91~
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen 20 filter is included in packaging operation to insure ~
the absence of any extraneous undissolved material in ;
the product.
Example O
Wettable Powder methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl3-methyl-amino]-thio]-N-14-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a~4,5-tetrahydro-2H-benz[g]indazole-3a-carbo~ylate. 30%
sodium alkylnaphthalenesulfonate 2% !~-sodium ligninsulfonate 2%
synthetic amorphous silica3%
~aolinite 63%
.' .. , :, . : . . . ~ ,. . ~ ,,. .. , ... . . :
. - ~ .. . .- , . - .:
,, . ~ ,, - : : , ,.. , : ..
. . - -: ~ 0 ~, The active ingredient, warmed to reduce viscosity, is sprayed onto the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 50 mesh screen.
E~amPle P
Solution methyl 7-chloro-2-[[N-[[[(hexyloxy)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino~-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 10%
isophorone 90%The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
E~mPl~ Q
Bait Granules methyl 4-[3-(4-chlorophenyl)-1-[l(ethoxycarbonyl)- -(l-methylethyl)amino]thio]-N-[4~(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 3.0%
blend of polyetho~ylated nonyl- 9.0%
phenols an sodium dodecylbenzene benzene sulfonates ground up corn cobs 88.0%
The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I, II and/or III can also be mised with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of effective pesticide protection.
Examples of other agricultural protectants with which compounds of the present invention can be mised or formulated are as follows.
Ins~icides:
3-hydro~y-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran) 0-[2,4,5-trichloro-a-(chloromethyl)benzyl]ophosphoric acid, 0',0'-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion) phosphorothioic acid, 0,0-dimethyl, 0-~-nitrophenyl ester (methyl parathion) methylcarbamic acid, ester with a-naphthol (carbaryl) methyl 0-(methylcarbamoyl)thiolacetohydro~amate (methomyl) N~-(4-chloro-Q-tolyl)-N,N-dimethylformamidine (chlordimeform) 0,0-diethyl-0-(2-isopropyl-4-methyl-6-pyrimidylphos-phorothioate (diazinon) -octachlorocamphene ~tosaphene) 30 0-ethyl 0-p-nitrophenyl phenylphosphonothioate (EPN) :-(S)-a-cyano-m-phenosybenzyl(lR,3R)-3-(2,2-dibromovinyl) -2,2-dimethylcyclopropanecarbosylate (deltamethrin) Methyl N',N'-dimethyl-N-[(methylcarbamoyl)osy]-l-thioosamimi-date (osamyl) cyano(3-phenosyphenyl)-methyl-4-chloro-a-(1-methyl-ehtyl)benzeneacetate (fenvalerate) .
, - - . ~ : - , ~ ,, - . , , , ~ ~
- ,, ~ . ., .. ~, : :
~Q~6!S
(3-pheno~yphenyl)methyl(~)-c s,~L~n~-3-(2,2-dichloro ethenyl)-2,2-dimethylcyclopropanecarboxylate (perme-thrin) a-cyano-3-pheno~ybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carbo~ylate (cypermethrin) O-ethyl-S-(D-chlorophenyl)ethylphosphonodithioate ', (profenofos) phosphorothiolothionic acid, 0-ethyl-0-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos).
Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzureon, methoprene, buprofezin, thiodicarb, acephate, azinphos-methyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathio, methamidiphos, monocrotphos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, metal-dehyde and rotenone.
.
Fun~icides:
methyl 2-benzimidazolecarbamate (carbendazim) :
tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) - 30 manganese ethylenebisdithiocarbamate ~maneb) 1,4-dichloro-2,5-dimethosybenzene (chloroneb) methyl l-(butylcarbamoly)-2-benzimidazolecarbamate (benomyl) ;, , : . ,: . .
: ~ , , . :
- - - , , :
2 ~ 65 1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dio~olan-2-ylmethyl]-lH-1,2,4-triazole (propiconazole) 2-cyano-N-ethylcarbamoy-2-methoxyiminoacetamide (cymoxanil?
1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-2-butanone (triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) 10 N-(trichloromethylthio)phthalimide (folpet) ~-:
l-[[tbis(4-fluorophenyl)]tmethyl]silyl]methyl]-1H-1,2,4-triazole.
~Ç1~118i ~
S-methyl l-(dimethylcarbamoyl)-N- (methylcarbamoyloxy)-thioformimidate S-methyl l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate ~.
N-isopropylphosphoramidic acid, 0-ethyl 0'-[4-(methylthio)-m-tolyl]diester (fenamiphos) ~ac~ericides:
tribasic copper sulfate streptomycin sulfate :
Acaricides:
senecioic acid, ester with 2-~Q~-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-cithiolo[4,5-B]quinoxalin-2-one 30 (oxythioquinox) -:
ethyl 4,4'-dichlorobenzilate (chlorobenzilate) 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethanol .
(dicofol) bis(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohe~yltin hydroxide (cyhexatin) trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo-thiazolidine-3-carboxamide (hexythiazox) -. . , . . . . . .- . ,.: , ~ . , .: ., - -. : ... ,. -.:: . - . . .... . .. . . . .. : . :.. . : . : . . .
s amitraz propargite 5. fenbutatin-o~ide .
~ioloical Bacillus thuringiensis Avermectin B.
Utility The compounds of the present invention ex-hibit activity against a wide spectrum of foliar and soil-inhabiting, livestock, household and public health arthropods. Those skilled in the art will recognize that not all compounds will be equally effective against all arthropods but the compounds of this invention display activity against economical- ~:
ly important pest species, such as grasshoppers and cockroaches including Berman or American roaches;
thrips; hemipterans: plant bugs (Miridae) such as tarnished plant bugs, lace bugs (Tingidae), seed bugs (Lygaeidae) such as cinch bugs, stink bugs (Pentatomidae), leaf-footed bugs (Coreidae) such as 25 squash bug, and red bugs and stainers (Pyrrocoridae) ::
such as cotton stainer; also homopterans such as whiteflies, aphids such as the green peach aphid, greenbug and cotton aphid, leafhoppers, spittlebugs and planthoppers such as aster leafhopper, potato leafhopper and rice planthoppers, psyllids such as pear psylla, scales (coccids and diaspidids) and mealybugs; coleopterans including weevils such as boll weevil and rice water weevil, grain borers, chrysomellid beetles such as Colorado po~ato beetle, flea beetles and other leaf beetles, coccinellid beetles such as Me~ican bean beetle.
. . - .: . - - . . ,. . .. . , . . . . : .. ~ , ~ ::. . -- .. .. ~ . .. : . .. - . . .. . . . - ... . . :
. . . . . . . . ~ .. . . .
.. .. . . . . , ., : . . - .
: . . . .
Activity is also shown against soil insects such as southern corn rootworm and wireworm;
lepidopterous larvae including noctuids such as fall armyworm, beet armyworm, other Spodoptera spp., .
Heliothis spp. such as virescens, Heliothis zea, cabbage looper, green cloverworm, velvetbean caterpillar, cotton leafworm, black cut- worm, and other noctuid cutworms and including pyralids such as European corn borer, navel orange- worm, and stalk/stem borers and including tortricids like codling moth and grape berry moth as well as other lepidopterous larvae such as pink bollworm and diamodback moth; and dipterans such as leaf-miner, soil maggots, midges, and tephritid fruit flies; house fly, Musca domestica; stable fly, Stomoxys calcitrans; black blow fly, Phormia reaina;
face fly, Musca autumnalis; black fly, Simulum meridionale; yellow fever mosquito, Aedes eaVPti;
German cockroach, Blattella aermanica; carpenter ants, Camponotus pennsylvanicus and eastern subterranean termite, ReticuLitermes flavipes. The pest control afforded by the compounds of the present invention is not limited, however, to these species.
The specific species, for which control is ~
esemplified below, are: fall armyworm, Spodoptera ~ .
frugiperda; tobacco budworm, Heliothis virescens; ~!
southern corn rootworm, Diabrotica undecimpunctata 30 howardi; aster leafhopper, Macrosteles fascifrons. `
The pest control afforded by the compounds of the present invention is not limited, however, to these species. ~
3~ Application -.
Arthropods are controlled in agricultural crops and animals and humans are protected by applying one or more of the compounds of this invention, in an ''."' ' . ., . . .- , . . . ...
.
~q31Q~6~
effective amount, to the locus of infestation, to the area to be protected, directly to the pests to be controlled, or to their environment. A preferred method of application is by spraying with spray equipment that distributes the compound on the foliage, in the soil, or to the plant part that is infested or needs to be protected. Alternatively, granular formulations of these compounds can be applied to soil or foliage or, optionally, incorporated into the soil. Either aerial or ground application can be used. Because of the diversity of behavior patterns and habitats of the animal and human health species, many different methods of application are employed. These include direct and residual sprays, baits, ear tags, soil treatment and many others.
The pyrazoline compound(s) of this invention can be applied directly, but most often application will be of a formulation comprising one or more com-pounds of this invention, in an agriculturally suit-able carrier or diluent. A most preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. The compound(s) can also be incorporated into baits which are consumed or in devices such as traps and the like that entice the arthropod to ingest or otherwise contact the tosicant compound(s).
The rate of application of Formula I, II or III compounds required for effective control will depend on such factors as the æpecies of arthropod to be controlled, the pest's life stage, its size, its location, the host crop, time of year of application, ambient moisture, temperature conditions, and the like. In general, application rates of 0.01 to 2 kg of active ingredient per hectare are sufficient ,: .. :: . . -. - - . ,. ; ................ ,, - ~ .,.. . -, - . - ., - :, . : . . ........................... . . .
, ,: .. ~ ., : , . . ................. .
,, , ~ :: ~ ., -. . . , s to provide effective control in large scale field operations under normal circumstances, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required for agricultural use, or 0.1 mg/ft2 to 20 mg/ft2 for home use, depending upon the factors listed above.
The following Examples demonstrate the con-trol efficacy of compounds of Formulae I, II and III
on specific arthropod pests wherein Compounds 1 through 55 are depicted in the E~amples and Tables A, B and C and summarized in Table D, respectively.
-)s Table D
R2 ~ O2CH3 N-N ~ ' O S Y
CMPD Rl R2 Y
1 CF3 H N(CH[CH3]2)CO2Et 2 CF3 H CO2~-BU
3 CF3 H N(n-Bu)2 4 CF3 5-Cl N(cH3)co2n-he CF3 H N(CH3)CO2n-BU
6 CF3 H N(CH3)co2Et 7 CF3 4-F N(CH3)CO2n-BU
8 CF3 H N(cH3)co2cyclohe~yl :
9 CF3 H ~ N(CH3)CO2n-octyl :
3~ CF3 H N(c~3)co2n-decyl 11 CF3 4-F N[CH(CH3)2]cO2Et : -12 CF3 H N(cH3)co2n-dode 13 CF3 H N(CH3)C
- g H N(cH3)c(o)oc8Hl7 144-145 0.88(t,3H), 1.21(m,12H), l.9(m,1H), 2.7(m,1H), `~ 2.9(m,2H), 3.5(m,3H), ,. 3.65(m,3H), 3.75(m,3H), 4.5(d, lH), 7.1(m,3H), :...
7.25(m,1H), 7.35(d,2H), . 25 7.6 ( d ,2H ) .
H N(CH3)c(O)ocloH2l 76-78 0.88(t,3H), 1.25(m,16H), l.9(m,1H), 2.7(m,1H), 2.9(m,2H), 3.5~s,3H), "7 3.66(~,3H), 3.75(m,3H), ' 30 4.5(d,lH), 7.15(m,3H), ~ .
.. . . .
7.25(m, lH), ? .35(d,2H), `
7.6 (d,2H).
.i~ .
, . . .
~ 35 .
.', ~' ' ~', ' ',: ' .
2~()Qt~iS
Example R2 Z m.p.C lH NMR (~ in ppm) _ _ _ 1D CDC13 . .
11 6-F N-[CH(CH3)2]C(O)OC2Hs 143-5 O.91(t,3H), 1.27td,3H), 1.35~d,3H), 1.3tm,lH), 2.75(m,2H), 3.05(m,lN), 3.67(s,3H), 3.75(m,3H), 4.5(m,2H), 7.25(m,3H), 7.45(d,2H), 7.6(d,2H).
12 H N(CH3)c(O)ocl2H25 0.88(t,3H), 1.26(m,20H), l.9(m,1H), 2.7(m,1H), 2.9¦m,2H), 3.5(~,3N), 3.66(s,3H), 3.75(m,3H), .S(d,lH), 7.1(m,3H), 7.25(m,1H), 7.35(d,2H), 7.6(d,2H).
13 H N(CH3)c(O)oc6Hl3 0.88(t,3H), 1.26(m,8H), l.9(m,1H), 2.7(m,1N), - 2.9(m,2H), 3.51(s,3H), 3.66(s,3H), 3.75(m,3H), 4.5(d,2H), 7.1(m,3H), :~ 25 7.25(m,1H), 7.35(d,2H), 7.6(d,2H).
. 14 7-Cl C(O)O-sec-C4H9 132 0088(t,3H), 1.3(m,3H), 1.6(m,2H), l.9(m,1H), ` 2.6-3.0(m,3H), 3.88(~,3H), 3.8(d,1H), 4.5(d,1H), 5.0(m,1H), 7.0(m,3H), 7.35(d,2N), 7.6(d,2H).
7-Cl N-tcH(cH3)2lc(o)oc2H5 152 O.9(t,3H), 1.26(d,3H), 1.35(d,3H), l.9tm,1H), ;` 35 2.7(m,1H), 2.9(m,2H), 3.67(s,3H), 3.8(m,3H), 4.5(m,2H), 7.14(m,2H), - 7.4(m,3H), 7.6(d,2H).
.. ..
2~0Q~65 ! -` 31 . .
E~ample R2 Z m.p. C lH NMR (6 i~ ppm) ~n CDC13 _ --16 7-Cl N(CH3)C(O)OC2H5 0.88(t,3H), l.9(m~1HJ, 2.65(m,1H), 2.9(m,2H), 3.49(6,3H), 3.66(~,3H), 3.8(m,3H), 4.5(d,lH), 7.07(m, 3H), 7.35(d,2H), 7.6(d,2H).
17 7-Cl N(CH3)c(O)oc8~l7 103-106 0.88(t,3H~, 1.23(m,12H), , l.9(m,1H), 2.65(m,1H), , 15 2.85(m,2H), 3.5(6,3H), 3.66(6,3H), 3.75(m,3H), :
4.45(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(~,2H).
18 6-F C(O)O-sec-C4H9 125-126 0.9(m,3H), 1.3(m,5H), ~
l.9(m,1H), 2.75(m,2H), ~;
3.0(m,1H), 3.7(6,3H), 3.8(d,lH), 4.5(d,lH), '~ 5.0(m,1H), 6.8(m,1H), ,.~ .~.
7.05(m,2H), 7.45(d,2H) .c 25 7.6(d,2H).
. ~ .
~0 19 7-Cl N(CH3)C(O)OC4Hg 125-127 0.82(m,3H), 1.2(m,4H), .5 1 . 9(m,lH), 2.65(m,lH), 2.85(m,2H), 3.5(6,3H), ~; .
` 3.66~s,3H), 3.7S(m,3H), â~ 4.45(d,1H), 7.05(m,3H), ~ 7.35(d,2H), 7.6(d,2H).
;~ 20 7-Cl N[cH(cH3)2]c(o)oc4H9 - 0.84(t,3H), 1.25(m,10H), ~-~ 1.9(m,1H), 2.65(m,1H), i 3.66(E,3H~, 3.7(m,3H), 4.45(m,2H), 7.15(m,2H), 7.4(m,3N), 7.6(d,2H).
J
. . :.
'~
., ~ .
~QQ~65 Example R2 Z m.p. C lH NMR (~ in ppm) S ~ - in CDC~3 21 7-Cl N(CH3)C(O)ocl2H25 0.88(t,3H), 1.2(m,20H), l.9(m,lH), 2.65(m,lH), 2.9(m,2H), 3.5(6,3H), 3.67(s,3H), 3.75(m,3H), 4.5(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
22 7-Cl N(CH3)C(O)O-cycloC6H11 87-91 0.8-1.7(BroDd m,lOH), 2.65(m,1H), 2.9(m,2H), 3.51(s,3H), 3.66(~,3H), 3.75(d,1H), 4.35(m,1H), 4.45(d,1H), 7.05(m,3H), 7.35(d,2H), 7.6(d,2H).
23 7-Cl N(CH3)C(O)O(CH2)20C4Hg - 0.9 ~t,3H3, 1.4 (m,4H) 1.9 (m,lH), 2.7 (m,lH?
2.9 (m,2H), 3.3 (m,4H) 3.5 (b,3H), 3.67 (s,3H), ` 3.9 (m,3H), 4.5 (d,lH), 7.1 (m,3H), 7.4 (d,2H), 7.6 ~d,2H).
24 7-Cl N(CH3)C(O)Ocl4H29 0.87 (t,3H), 1.26 (m,24H), 1.9 (m,lH), 2.65 (m,lH), ' 2.9 ~m,2H), 3.5 (s,3H), r. 3.68 (s,3H), 3.75 (m,3H), ' 30 4.47 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.57 (d,2H).
7-Cl N~CH3)C(O)OC16H33 ~ 0.87 (t,3H), 1.26 (m,28H), 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 (s,3H), 3.75 (m,3H), 4.47 (d,lH), 7.C5 (m,3H), 7.35 ~d,2H), 7.6 (d,2H).
.
~` :
.
Example R2 Z m.p. C lH NMR (~ in ppm) ~ CD~13 26 7-Cl N(cH3)c(o)ocl8H37 ~ 0.9 (t,3H), 1.26 (m,32H), - 1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.67 (m,3H), 3.75 (m,3H), ,~ 4.5 (d,lH), 7.05 (m,3H), 7.35 (d,2H), 7.6 (d,2Ht.
27 7-Cl N(cH3)c(o)oc22H45 0.8B ~t,3H), 1.26 (m,407a), -1.9 (m,lH), 2.65 (m,lH), 2.9 (m,2H), 3.5 (s,3H), 3.65 (m,3H), 3.75 (m,3H), 4.4B (d,lH), 7.06 (m,3H), 7.35 (d,2H), 7.6 (d,2H).
28 7-Cl N(CH3)c(O)O(cH2)20(cH2)2oc4H9 0.91 (t,3H), 1.4 (m,4H), - 20 1.9 (m,lH), 2.7 (m,lH), 2.9 (m,2B), 3.5 (s,3H), 3.67 (s,3H), 3.7 tm~9H)~ -4.0 (m,lH), 4.2 (m,lH), , 4.5 (d,lH), 7.6 (m,3H), 7.4 (d,2H), 7.6 (d,2H).
... . .
,~ , .
.~ " .
',7 ':
~), '.
., '.''~.
... . : .
', , 2(~Q~65 E~ample 29 1-(4-chlorophenyl~-5-(4-fluorophenyl~-4,5-dihydro-N- ;
'[4-(trifluoromethyl)phenyl]-N-lN'-(l-methylethyl)-N'-(ethoxycarbonyl)aminothiol]-lH-pyrazole-3-_carboxamide Step A: Ethyl (chlorosulfenyl)(l-methylethyl)-carbamate To a solution of ethyl (l-methylethyl)carbamate (13.1 9, 0.1 mol) in 100 ml of methylene chloride cooled to 0C was added sulfur dichloride (11.3 9, 0.11 mol) in one portion. While maintaining the temperature of the mixture at 0C, pyridine (8.7 g, 0.11 mol) was added dropwise over eleven minutes.
After complete addition of the pyridine the temperature was allowed to rise to room temperature and stirring was continued for additional 1.5 hours.
The mixture was let stand overnight. Methylene chloride was evaporated under vacuum and 100 ml hexane was added. Filteration of pyridine hydrochloride and evaporation of hexane resulted in an orange oil which was distilled in a Kugelrohr apparatus to give 12.5 9 of the title Compound B.P.:
64-80 (bath temp.) ~.
Step B: 1-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyl]-N-lN'-(l-methylethyl)-N'-(ethoxycarbonyl)-aminothiol]-lH-pyrazole-3-carbo~amide To a solution of 1-(4-chlorophenyl)-5-(~-fluoro-phenyl)-4,5-dihydro-N-[4-(trifluoromethyl)phenyll-lH-pyrazole-3-carboxamide (0.95 9, 0.002 mol) in 10 ml :
.. : .. . . . .
2C~QQ~65 . .
of methylene chloride cooled to QC was added triethylamine (0.25 9) followed by the title compound of Step A (0.5 9, 0.0025 mol). The reaction mi~ture was allowed to warm to room temperature with stirring for one hour. Methylenç chloride (50 ml) was added and the mi~ture was washed with water, dried over magnesium sulfate and filtered. The solvent was evaporated and the residue was purified by silica gel column chromatograph using hexane:ether (2:1~ as the eluent. Obtained 1.0 g of the title compound, m.p.: 136-137C, 'H-NMR (CDC13); ~ 7.7 (d,ZH), 7.4 (~, 2H), 7.0 (m, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 15 4.5 (m, lH), 3.75 (m, 3H), 3.05 td of d, lH) 1.3 (d of d, 6H), 0.87 (t, 3H).
.
Example 30 3,9-bis-(4-chlorophenyl)-N-[4-(trifluoromethyl)-20 phenyl]-N-[N'-(l-methylethyl)-N'-(etho~ycarbonyl)-aminothioll-4.5-dihydro-lH-pyraz~lç-l-car~Qxamide ,: i . : .
To a solution of 3,4-bis-(4-chlorophenyl)-N-[4-(trifluoromethyl)phenyl)~-4,5-dihydro-lH-pyrazole-25 l-carboxamide (0.466 9, 0.001 mol) in 5 ml of - methylene chloride cooled to 0C was added 0.3 9 of triethylamine and ethyl (chlorosulfenyl)(l-methyl-: ethyl)carbamate (0.5 9). The mi~ture was allowed to warm to room temperature and let stand overnight. 20 - 30 ml CH2C12 was added and the mi~ture was washed with water and dried over MgSO4 and filtered. The solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography using - CH2C12:Butylchloride mi~ture (1:1) as a primary eluent followed by ether. The title compound was obtained in high purity (0.28 9), m.p.: 65-68C.
:
: , ' .: : .
,: , . . .
.
.. ... . ..
~?a!Q~.65 lH-NMR (CDC13), ~ 7.65 ~d, 2H), 7.5 (d, 2H), 7-27 (d, 2H), 7.17 (S, 4H), 7.0 (d, 2H), 4.6-4.3 (m, 3H), 3.95 (d of d, lH), 3.8 (q, 2H), 1.3 (m, 6H), 0.95 (t, 3H).
The following additional Examples (Tables B
and C) employed procedures similar to those described in the previous E~amples 29 and 30 or in the disclosed literature.
.
~ 15 . ' ~ .
. .
:.
:. ~O
.
35 ~
. .
., .
, ,. , .- :: . - -2(~Q(:~6S
~able B
Cl ~ N S
~ ~ C~3 Example X m.p.C 'H-NMR (6 in ppm) in CDC13 ,~ . .
N[cH(cH3)2]c(o)oc4H9 165-170 7.23 (d, 2H), ?.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), 5.2 (d of a, lH), 4.5 (M, lH), 3.75 (M, 3H), 3.1 (a of d, lH), 1.4-1.1 (M, lOH), .85 (t, 3H) 32 N[CH(CH3)(c2Hs)]c(O)oc2H5 ~ 7.23 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), 5.2 (d of d, lH), 4.5 (N, lH), 3.75 (M, 3H), 3.1 (d of d, lH), 1.8-1.1 ;-(M, 5H), 0.9 (M, 6H).
.
2~Q~6ti Example X m.p.C 'H-NMR ~ ~n ppm) ~n CDC13 .
:
,. .
33 C(O)OCH(CH3)(C2H5) 159-161 7.25 (d, 2H), 7.55 (d, 2H), 7.0 (M, 6H), 6.25 (d, 2H), 0 5.2 (d of d, lH), 5.0 ~M, lH), 3.75 (d of d, lH3, 3.1 (d of d, lH), 1.65 (M, 2H), 1.28 (d, 3H), 0.9 (t, 3H).
34 N(CH3)C(O)O(cyclo C6Hll) 147-150 7.2 (d, 2H), 7.4 (d, 2H), 7.0 (M, 6H), 6.3 (d, 2H), -5.2 (d of d, lH), 4.3 (M, lH), 3.7 (d of d, lH), 3.5 (5, 3H), 3.2 (d of d, lH), l.B-0.9 (M, lOH).
':
. ".
. :
~"' ' ' :'.` ..
.. . .
... :
.. . .
-:.
~`', , ' -' .
, . . .
,. . . .
;~ . :
~,: - ,. , -: . : : . - - . .: . . : : . .
::: . - : . , . . ,: . - . . . . .
2~ S
~ 39 .
Table C
.
. 5 :
, .
10 C~ ~R3 : N ~
O=Cj . :~, ~ ~Q
R1 :'-''`.` "' ~i 20 .. ~ .
,j. :
- EX- Q R3 Rl m.p.C 'H-NMR (~ in ppm) ~` ~_ , ,, ~ 35 S-N(CH3)CIO)O-ce~-C4H9 Cl CF3 B3-84 7.B-6.9 ~m, 128), .~, 4.6-4.3 (M, 3H), 4.0 (M, lH), 3.52 (S, 3H), :'! 1.25 (M, 2H), 1.0-0.7 . (M, 6H).
i. 30 36 S-C(0)0-~ec-C4Hg Cl CF3 78-80 7.7-7.0 (M, 12H), 5.0 M, lH), 4.45 (M, 2H), ~.0 (M, lH), 1.6 (M, .~ 2H), 1.3 (d, 3H), o.g . . . .
; (t, 3H).
'^ 35 . ,' .
~.
:, ... . - . . : : :. .. : ,: .,- , . . . .
: . - . : ~ ~ . . : .
.
: , . .. . . . . .
,i ~ . - . . ,: . i - .: : -- .
,: .- , ; ,::
2(~0~65 EX- Q R3 Rl m.p.C 'H-NMR (S in ppm) ---37 S-C(O)O-6ec-C4Hg Cl Cl 66-69 7.4-6.9 (M, 12H), 5.0 (M, lH), 4.5 (M, 2H), 4.0 (M, lH), 1.6 (M, 2H), 1.28 (d, 3H), 0.9 (M, 3H), ,:
38 C2CH3 Cl CF3 151-154 7.7-7.0 (m, lZH), 4.7 (d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 (s,3H).
39 COCH3 F C~3 157-159 7.7-7.0 (m,12H), 4.7 ; (d,d,lH), 4.5 (d,d,lH), 4.1 (d,d,lH), 3.86 (s,3H). i`
. .
40 S-N~cH(cH3)2)so2c2H5 Cl CF3 oil 7.65 (m,2H), 7.25 (m,4H), 7.05 (m,lH), 4.6-3.9 (m,3H), 3/65 (m,lH), 3.03 (~,2H), 1.36 (t,3H), 1.24 (d,6H).
.. . .
41 COCB3 Cl CF3 166-168 7.6-7.0 ~m,12H?, 4.7-4.0 (m,3H), 2~3 (s,3H).
..
42 COCH3 F Cl 187-190 7.5-7.~ (m,12H), 4.6 (m,lH), 4.4 ~m,lH), 4.0 (m,lH), 2.26 (6,3H). ,~
~:
.
'' ,.;, ,. :
`~
ZC~ 65 41 ~:
~' ',' 5 EX- Q R3 Rl m.p.C 'H NMR (~ i~ ppm) ~MPLE .
43 COCH3 F Br181-186 7.6-7.0 (m,12H), 4.65 (m,lH~, 4.4 (m,lH), 4.0 (m,lH), 2.25 (~,3H).
44 CO2Me F CF380-86 :
~ 15 45 COPh F CF3176-179 . ~
46 COEt Cl CF3 169-170 . 47 EtCOCO Cl CF3 166-167 , 20 ,, 48 CO-n-9u Cl CF3 60-62 ~, .~^ 49 COCH3 Cl Cl 205-206 ~ A ' ~, , 25 50 COEt Cl Cl lS7-158 :~,~ . , '~ 51 CO2Me Cl Cl 162-166 '.' ~, 52 4-ClPhCO Cl CF3 209-211 ., 30 - 53 t-BuCO Cl CF3 140-145 ;
-. 54 PhOCO Cl CF3 150-155 ' ;:
~ .
r, ''. ' ' :. , ~ . -,, '. '' ~.. ' ` :" ' 2(~)Q~5 Example 55 N-acetyl-3,9-bis(4-chlorophenyl)-4,5-dihydro-N-[9-(trifluoromethyl)phenyl]-lH-pyrazole-l-~_sarboxamide The compound of Step D of E~ample 6 (0.65 9) was dissolved in tetrahydrofuran (20 ml) and treated with 60~ sodium hydride in oil (0.12 9). After the evolution of hydrogen was complete (30 minutes), acetic anhydride (0.6 ml) was added and the mi~ture was stirIed at room temperature for 16 hours. The reaction was diluted with saturated aqueous ammonium chloride solution (15 ml~ and ethyl acetate (30 ml).
The organic layer was dried with magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel with hexanes/ethyl acetate (3:1) as eluent. Addition of methanol (10 ml) to the product gave, after filtration, the title compound (0.4 9). m.p. 166 to 168C.
-~ NMR (CDC13) 7.6-7.0 (m, ArH, 12H), 9.7-4.0 (m, 3H, CH and CH2), 2.3 (s, COCH3, 3H).
.
,, :
,, ', :
,~ : ' .
:~, ,~
,.
'.
' -.
- ,,. -, , ,,: - . . ~, .. ,., . ,, . ~,.. , . .. : . ; -.. - . . ~,. . .,, i, ,,, ~ . : . ;
. . . . .~ . . : . .: :
2~10Q~6S
`: . :
. 43 Table 1 : ':
1~)~N--N ~/~
O ~
~B
:~
'. R2 B R8 Rg 4-CF35-Cl H Me OEt ~ 4-CF35-Cl Me Me OEt .. 20 9-CF3 H CO2Me Me OEt 4-Cl H CO2Me Me OEt ' , 4-Br H CO2Me Me OEt ~,~ 4-OCF3 H CO2Me Me OEt :
`. 4-CF35-Cl CO2Me Me OEt .~ 25 4-C15-Cl C02Me Me OEt ~' 4-OCF35-Cl CO2Me Me OEt .~ 4-CF35-CF3 CO2Me Me OEt 4-CF35-F CO2Me Me OEt 4-CF35-Cl Ph Me OEt 4-CF35-C14-Cl-Ph Me OEt 4-CF35-Cl CO2Et Me OEt - 4-CF35-Cl H Me O-n-Bu 4-CF34-F H Me O-n-Bu 4-CF3 H Me Me O-n-Bu 4-CF35-Cl Me Me O-n-Bu .
; 4-CF35-Br Me Me O-n-Bu ~, , .
,. ~' . .
:.-.......... :
21?Q~i5 :
Rl R2 B R8 Rg :-4-CF3 4-F Me Me O-n-8u 4-CF3 H CV2Me Me O-n-Bu 4-Cl H CO2Me Me O-n-Bu 4-Br H CO2Me Me O-n-Bu 4-OCF3 H CO2Me Me O-n-Bu 4-CF3 5-Cl CO2Me Me O-n-Bu .~ 4-C1 5-Cl CO2Me Me O-n-Bu '.- 4-Br 5-Cl CO2Me Me O-n-Bu -: 4-OCF3 5-Cl CO2Me Me O-n-Bu 4-CF3 5-Br CO2Me Me O-n-Bu 4-C1 5-Br CO2Me Me O-n-Bu ~ 4-Br S-Br CO2Me Me O-n-Bu ;. 4-OCF3 5-Br CO2~e Me O-n-Bu 4-CF3 4-F CO2Me Me O-n-Bu . 20 4-C1 4-F CO2Me Me O-n-Bu 9-Br 4-P C02Me Me O-n-E3u ; 4-OCF3 4-F C02Me Me C)-n-Bu 4-CF3 5-CF3 CO2Me Me O-n-Bu 4-CF3 5-F CO2Me Me O-n-Bu :
4 CF3 5-Cl Ph Me O-n-Bu ~, - 4-CF3 5-C1 4-Cl-Ph Me O-n-Bu 4-CF3 5-Cl CO2Et Me O-n-Bu 4-CF3 5-Cl Me Me O-n-hexyl .~ 4-CF3 H CO2Me Me O-n-hexyl 3 4-Cl H CO2Me Me O-n-hexyl ~: -4-Br H CO2Me Me O-n-hexyl 4-OCF3 H C02Me Me O-n-hexyl 4-CF3 5-Cl C02Me Me O-n-hexyl 4-Cl S-Cl CO2Me Me O-n-hexyl .:
4-Br 5-Cl CO2Me Me O-n-hexyl . ~.
4-OCF3 5-Cl CO2Me Me O-n-hexyl : ::
4-CF3 5-Br CO2Me Me O-n-hexyl .,`1 ..
. . , , ; ' ~.
- .. ~ - ~ : . . ' ., ,: , . . :, , ., , . . ~ . . . . . .. . .. ..
2n~6s Rl R2 B R8 Rg 4-C1 5-Br C02Me Me O-n-he2~yl 4-Br 5-Br CO2Me Me O-n-hexyl 4-OCF3 S-Br CO2Me Me O-n-he~yl q-CF3 4-F CO2Me Me O-n-heJcyl 4-C1 4-F CO2Me Me O-n-hexyl 4-Br 4-F C02Me Me O-n-he:~yl 4-OCF3 4-F CO2Me Me O-D-hexyl 4-CF3 5-CF3 C02Me Me O-n-he~yl 4-CF3 5-F C02Me Me O-n-he2~yl 4-CF3 5-Cl Ph Me O-n-he~yl 9-CF3 5-C1 4-Cl-Ph Me O-n-hexyl 4-CF3 5-Cl CO2Et Me O-n-hexyl 4-CF3 S-Cl Me Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl : 4-Cl H CO2Me Me O-n-octyl 4-Br H CO2Me Me O-n-octyi 4-OCF3 H CO2Me Me O-n-octyl 4-CF3 5-Cl CO2Me Me O-n-octyl 4-Cl S-Cl CO2Me Me O-n-octyl - 4-Br S-Cl CO2Me Me O-n-octyl 4-OCF3 S-Cl CO2Me Me O-n-octyl 4-CF3 S-Br CO2Me Me O-n-octyl 4-C1 5-Br CO2Me Me O-n-octyl ~: 4-Br 5-Br CO2Me Me O-n-octyl 4-OCF3 5-Br CO2Me Me O-n-octyl 4-CF3 4-F CO2Me Me O-n-octyl 4-C1 4-F CO2Me Me O-n-octyl -~ 4-Br 4-F CO2Me Me O-n-octyl 4-OCF3 4-F CO2Me Me O-n-octyl 4-CF3 5-CF3 CO2Me Me O-n-octyl 4-CF3 S-F CO2Me Me O-n-octyl 2~1~Q~S
.
1 R2 B R8 Rg 4-CF35-Cl Ph Me O-n-octyl 4-CF35-C14-Cl-Ph Me O-n-octyl ~-~ 4-CF35-Cl CO2Et Me O-n-octyl 4-CF35-Cl Me Me O-n-decyl -.
4-CF3 H CO2Me Me O-n-decyl . 4-Cl H CO2Me Me O-n-decyl 4-Br H CO2Me Me O-n-decyl 9-OCF3 H CO2Me Me O-n-decyl 4-CF35-Cl CO2Me Me O-n-decyl 4-C15-Cl CO2Me Me O-n-decyl 9-Br 5-Cl CO2Me Me O-n-decyl 4-OCF35-C1 ~2Me Me O-n-decyl 4-CF35-Br CO2Me Me O-n-decyl ;~ 4-C15-Br CO2Me Me O-n-decyl !
4-Br 5-Br CO2Me Me O-n-decyl 4-OCF35-Br CO2Me Me O-n-decyl ~. .
4-CF34-F CO2Me Me O-n-decyl . 4-C14-F CO2Me Me O-n-decyl ~` 4-Br 4-F CO2Me Me O-n-decyl .-, 25 4-OCF34-F CO2Me Me O-n-decyl 4-CF35-CF3 CO2Me Me O-n-decyl 4-CF35-F CO2Me Me O-n-decyl 4-CF~ 5-Cl Ph Me O-n-decyl 4-CF35-C14-Cl-Ph Me O-n-decyl 4-CF35-Cl CO2Et Me O-n-decyl 4-CF35-Cl Me Me O-n-dodecyl . 4-CF3 H CO2Me Me O-n-dodecyl 4-Cl H CO2Me Me O-n-dodecyl 4-Br H CO2Me Me O-n-dodecyl 4-OCF3 H CO2Me Me O-n-dodecyl 4-CF35-Cl CO2Me Me O-n-dodecyl , ' ~.7 . :,`, 2~ Q~65 ;
Rl R2 B R8 Rg 7, 4-C1 5-Cl CO2Me Me O-n-dodecyl 4-Br 5-Cl C02Me Me O-n-dodecyl 4-OCF3 5-Cl CO2Me Me O-n-dodecyl 4-CF3 5-Br CO2Me Me O-n-dodecyl 4-Cl S-Br CO2Me Me O-n-dodecyl 4-Br 5-Br CO2Me Me O-n-dodecyl 4-OCF3 5-Br CO2Me Me O-n-dodecyl 4-CF3 4-F CO2Me Me O-n-dodecyl 4-C1 4-F CO2Me Me O-n-dodecyl 4-Br 4-F CO2Me Me O-n-dodecyl 4-OCF3 4-F CO2Me Me O-n-dodecyl 4-CF3 5-CF3 CO2Me Me O-n-dodecyl 4-CF3 5-F CO2Me Me O-n-dodecyl 4-CF3 5-Cl Ph Me O-n-dodecyl 204 CF3 5-C1 4-Cl-Ph Me O-n-dodecyl 4-CF3 5-Cl CO2Et Me O-n-dodecyl .
4-CF3 5-Cl Me Me O-sec-Bu 4-CF3 H CO2Me Me O-sec-Bu , 4-Cl H CO2Me Me O-sec-Bu 25 4-Br H CO2Me Me O-sec-Bu 4-OCF3 H CO2Me Me O-sec-Bu ~' 4-CF3 5-Cl CO2Me Me O-sec-Bu 4-C1 5-Cl CO2Me Me O-sec-Bu 4-Br 5-Cl CO2Me Me O-sec-Bu 4-OCF3 5-Cl CO2Me Me O-sec-Bu 4-CF3 5-Br CO2Me Me O-sec-Bu 4-C1 5-Br CO2Me Me O-sec-Bu ;, -4-Br 5-Br CO2Me Me O-sec-Bu 4-OCF3 5-Br CO2Me Ne O-sec-Bu 354-CF3 4-F CO2Me Me O-sec-Bu 4-C1 4-F CO2Me Me O-sec-Bu ,.
:
..
- - , .
Æ(~t:)Q16S
..
Rl R2 ~ R8 Rg --4-Br 4-F CO2Me Me O-sec-Bu 4-OCF34-F CO2Me Me O-sec-8u -~ 4-CF35-CF3 CO2Me Me O-sec-Bu 4-CF35-F CO2Me Me O-sec-Bu 4-CF35-CI Ph Me O-sec-Bu 4-CF35-C14-Cl-Ph Me O-sec-Bu 9-CF35-Cl CO2Et Me O-sec-Bu 4-CF35-Cl Me Me OCH2CH2OEt 4-CF3 H COzMe Me OCH2CH2Et 4-Cl H CO2Me Me OCH2CH2Et 4-Br H CO2Me Me OCH2CH2OEt 4-OCF3 H CO2Me Me OCH2CH2OEt " 4-CF35-Cl CO2Me Me OCH2CH2Et 4-C15-Cl c02Me Me OCH2CH2OEt 4-~r 5-Cl CO2Me Me OCH2CH2OEt 4-OCF35-Cl CO2Me Me OCH2CH2OEt 4-CF35-Br CO2Me Me OCH2CH2OEt 4-C15-Br CO2Me Me OCH2CH2OEt i, 4-~r 5-Br CO2Me Me OCH2CH2OEt ", 25 4-OCF35-Br CO2Me Me OCH2CH2OEt ,!~i 4-CF34-F CO2Me Me OCH2CH2Et .. 4-C14-F CO2Me Me OCH2CH2OEt '~ 4-Br 4-F CO2Me Me OCH2CH2OEt 4-OCF34-F CO2Me Me OCH2CH2OEt - 4-CF35-CF3 CO2Me Me QCH2CH2OEt . 4-CF35-F CO2Me Me OCH2CH2OEt 4-CF35-Cl Ph Me OCH2CH2OEt 4-CF35-C14-Cl-Ph Me OCH2CH2OEt 4-CF35-Cl CO2Et Me OCH2CH2OEt 4-CF35-Cl Me Me OCH2CC13 . 4-CF3 H CO2Me Me OCH2CC13 4-Cl H CO2Me Me OCH2CC13 4-Br H CO2Me Me OCH2CC13 , .
' ' ':
, - ~
2~ 65 Rl R2 B R8 Rg .
4-OCF3 H CO2Me Me OCH2CC1 4-CF35-Cl CO2Me Me OCH2CC1 4-C1 5-Cl CO2Me Me OCH2CC1 4-Br 5-Cl CO2Me Me OCH2CC1 ~- 10 4-OCF35-Cl CO2Me Me OCH2CC1 4-CF35-Br CO2Me Me OCH2CC1 4-C1 5-Br CO2Me Me OCH2CC1 4-Br 5-Br CO2Me Me OCH2CC1 4-OCF3 5-Hr CO2Me Me OCH2CC1 4-CF3 4-F CO2Me Me OCH2CC1 4-Cl 4-F CO2Me Me OCH2CC1 4-E~r 4-F C02Me Me OCH2CC1 4-OCF3 4-F CO2Me Me OCH2CC1 4-CF3 5-CF3 CO2Me Me OCH2CC1 9-CF35-F CO2Me Me OCH2CC1 4-CF3 5-Cl Ph Me OCH2CC1 9-CF3 5-C1 4-Cl-Ph Me OCH2CC1 ' 4-CF3 5-Cl CO2Et Me OCH2CC1 9-CF3 5-Cl Me Me OCH2CF3 4-CF3 H CO2Me Me OCH2CF
9-Cl H CO2Me Me OCH2CF3 4-Br H CO2Me Me OCH2CF3 ; 4-OCF3 H CO2Me Me OCH2CF3 4-CF35-Cl CO2Me Me OCH2CF3 ` ,~ 4-C1 5-Cl C02Me Me OCH2CF3 4-Br 5-Cl CO2Me Me OCH2CF3 4-OCF35-Cl CO2Me Me OCH2CF3 : 4-CF35-Br CO2Me Me OCH2CF3 4-C1 5-Br CO2Me Me OCH2CF3 5-Br CO2Me Me OCH2CF3 4-OCF35-Br CO2Me Me OCH2CF3 ~' , .
;,' '' ' 21~Q~65 Rl R2 B R8 Rg 4-CF3 4-F CO2Me Me OCH2CF3 4-C1 4-F CO2Me Me OCH2CF3 4-Br 4-F CO2Me Me OCH2CF3 4-OCF3 4-F CO2Me Me OCH2CF3 4-CF3 5-CF3 CO2Me Me OCH2CF3 4-CF3 5-F CO2Me Me OCH2CF3 4-CF3 5-Cl Ph Me OCH2CF3 4-CF3 5-C1 4-Cl-Ph Me OCH2CF3 ` 4-CF3 5-Cl CO2Et Me OCH2CF3 4-CF3 5-Cl Me Me OCH2CO2Et 4-CF3 H CO2Me Me OCH2CO2Et 4-Cl H CO2Me Me OCH2C2Et 9-Br H CO2Me Me OCH2CO2Et 4-OCF3 H CO2Me Me OCH2CO2Et 4-CF3 5-Cl CO2Me Me OCH2C2Et 4-C1 5-Cl CO2Me Me OCH2CO2Et 4-Br 5-Cl CO2Me Me OCH2CO2Et 4-OCF3 5-Cl CO2Me Me OCH2CO2Et 4-CF3 5-Br CO2Me Me OCH2CO2Et 4-C1 5-Br CO2Me Me OCH2CO2Et 4-Br 5-Br CO2Me Me OCH2CO2Et 4-OCF3 5-Br CO2Me Me OCH2CO2Et 4-CF3 4-F CO2Me Me OCH2CO2Et . 4-C1 4-F CO2Me Me OCH2CO2Et 4-Br 4-F CO2Me Me OCH2CO2Et 4-OCF3 4-F CO2Me Me OCH2C2Et 4-CF3 5-CF3 CO2Me Me OCH2CO2Et 4-CF3 5-F CO2Me Me OCH2CO2Et 4-CF3 5-Cl Ph Me OCH2CO2Et 4-CF3 5-C1 4-Cl-Ph Me OCH2CO2Et 4-CF3 5-Cl CO2Et Me OCH2CO2Et .~'.
... .
' : . ' . . .. . . ... . .. . . ..
~ - .
2n~Q~6s Rl R2 B R8 R9 9-CF3 H H Me F .
4-CF3 5-Cl H Me F
4-CF3 5-Br H Me F
^. 4-CF3 4-F H Me F
4-CF3 H Me Me F
4-CF3 5-Cl Me Me F
4-CF3 5-Br Me Me 4-CF3 4-F Me Me F
4-CF3 H CO2Me Me F
4-Cl H CO2Me Me F
4-~r H CO2Me Me F
~`: 4-OCF3 H C2M~ Me F
4-CF3 5-Cl CO2Me Me F
4-C1 5-Cl CO2Me Me F
4-Br 5-Cl CO2Me Me F
4-OCF3 5-Cl CO2Me Me F
. 4-CF3 5-Br CO2Me Me F
4-C1 5-Br CO2Me Me F
.~ 4-8r 5-Br CO2Me Me F
4-OCF3 5-Br CO2Me Me F
4-CF3 4-F CO2Me Me F
4-C1 4-F CO2Me Me F
4-Br 4-F CO2Me Me F
4-OCF3 4-F CO2Me Me F :
` 30 4-CF3 S-CF3 CO2Me Me F
.~ 4-CF3 5-F CO2Me Me F
4-CF3 5-Cl Ph Me F
. 4-CF3 5-C1 4-Cl-Ph Me F -`
4-CF3 5-Cl CO2Et Me F :
4-CF3 5-Cl CO2Me Me piperidino . 4-CF3 4-F Me Me piperidino 4-CF3 Cl CO2Me Me morpholino .
, ' .' .. . .
: , .
2~ 6S
Rl R2 B R8 Rg --4-OCF3 Cl CO2Me Me morpholino 4-CF3 S-Cl CO2Me Me n-Pr 4-OCF3 5-Cl CO2Me Me n-Pr 4-CF3 5-Br CO2Me Me sec-Bu 4-C1 5-Br CO2Me Me ~ec-Bu 4-Elr 5-Br CO2Me Me sec-Bu 4-OCF3 5-Br CO2Me Me sec-Bu 4-CF3 4-F CO2Me Me 4-Cl-Ph 4-C1 4-F CO2Me Me 4-Cl-Ph -,: 15 4-Br 4-F CO2Me Me 4-Cl-Ph 4-OCF3 4-F CO2Me Me 4-Cl-Ph ~
4-CF3 5-Cl Me Et OCH2CC13 ~ ~. .
4-CF3 H CO2Me Et NEt2 `~
4-Cl H CO2Me Et NEt2 `
4-Br H CO2Me Et NEt2 4-OCF3 H CO2Me Et NEt2 , 9-CF3 5-Cl CO2Me Et 2,6-di-Me-morpholino ;
4-C1 5-Cl CO2Me Et 2,6-di-Me-morpholino 4-Br S-Cl CO2Me Et 2,6-di-Me-morpholino 4-OCF3 5-Cl CO2Me Et 2,6-di-Me-morpholino 4-CF3 5-Cl Me iPr OEt 4-CF3 H CO2Me iPr OEt 4-Cl H CO2Me iPr OEt 4-Br H CO2Me iPr OEt 4-OCF3 H CO2Me iPr OEt 4-CF3 5-Cl CO2Me iPr OEt 4-C1 5-Cl CO2Me iPr OEt ;
4-Br S-Cl CO2Me iPr OEt 4-OCF3 5-Cl CO2Me iPr OEt ...
4 CF3 S-Br CO2Me iPr OEt -4-C1 5-Br CO2Me iPr OEt :
~ .
,~. . . . .
~?0~65 . Rl R2 B R8 Rg 4-Br 5-Br CO2Me iPr OEt 4-OCF3 5-Br CO2Me iPr OEt 4-CF3 4-F CO2Me iPr OEt 4-C1 4-F CO2Me iPr OEt 104-E~r 9-F CO2Me iPr OEt .~ 4-OCF3 4-F CO2Me iPr OEt 4-CF3 5-CF3 CO2Me iPr OEt 4-CF3 5-F CO2Me iPr OEt 4-CF3 5-Cl Ph iPr OEt 4-CF3 5-C1 4-Cl-Ph iPr OEt 4-CF3 5-Cl C02Et iPr OEt 4-CF3 5-Cl CO2Me Me ON~(CH3)SCH3 4-CF3 5-Cl CO2Me Me 2,3-dihydro-2,2-dimethylbenzofuranyl 2û oxy-7 4-CF3 5-Cl CO2Me Me l-naphtho~y -~ 4-CF3 5-Cl Me iPr O-n-Bu 4-CF3 H CO2Me iPr O-n-Elu 4-Cl H CO2Me iPr O-n-Bu .~ 25 4-Br H CO2Me iPr O-n-Bu -4-OCF3 H CO2Me iPr O-n-Bu 4-CF3 5-Cl CO2Me iPr O-n-Bu :
. 4-C1 5-Cl CO2Me iPr O-n-Bu 4-Br 5-Cl CO2Me iPr O-n-Bu ~; 30 4-OCF3 5-Cl CO2Me iPr O-n-Bu 4-CF3 5-Br CO2Me iPr O-n-Bu 4-C1 5-Br CO2Me iPr O-n-Bu : 4-Br 5-Br CO2Me iPr O-n-Bu 4-OCF3 5-Elr CO2Me iPr O-n-Bu 4-CF3 4-F CO2Me iPr O-n-Bu 4-C1 4-F CO2Me iPr O-n-Bu 4-Br 4-F CO2Me iPr O-n-Bu ',';
:
; ; ~:' ' 2~Q~6S
.
Rl R2 E3 R8 Rg 5 . - . ._ .
4-OCF3 4-F CO2Me iPr O-n-Bu 4-CF3 5-CF3 CO2Me iPr O-n-Bu ~.
4-CF3 5-F CO2Me iPr O-n-Bu ~ f 4-CF3 5-Cl Ph iPr O-n-Bu 10 4-CF3 5-C1 4-Cl-Ph iPr O-n-Bu `
4-CF3 5-Cl CO2Et iPr O-n-Bu 4-CF3 H CO2Me iPr OCH2CO2Me .:
4-CF3 5-Cl CO2Me iPr OCH2CO2Me 4-CF3 5-Br CO2Me iPr OCH2CO2Me - 15 4-CF3 4-F CO2Me iPr OCH2CO2Me ~:~ 4-CF3 H CO2Me iPr NMe2 :~ 4-Cl H CO2Me iPr NMe2 4-Br H CO2Me iPr NMe2 9-OCF3 H CO2Me iPr NMe2 20 4-CF3 S-Cl CO2Me iPr NEt2 .) 4-C1 5-Cl CO2Me iPr NEt2 4-~r 5-Cl CO2Me iPr NEt2 4-OCF3 5-Cl CO2Me iPr NEt2 .
q 4-CF3 5-Br CO2Ne iPr piperidino ; 25 4-C1 5-~r CO2Me iPr piperidino :
4-13r 5-BI CO2Me iPr piperidino 4-OCF3 5-Br CO2Me iPr piperidino ~ -4-CF3 4-F CO2Me iPr Et 4-C1 4-F CO2Me iPr Et . .
: 30 4-Br 4-F CO2Me iPr Et ~: 4-OCF3 4-F CO2Me iPr Et .. ~ 4-CF3 H H CH2Ph OEt .. 4-CF3 5-Cl H CH2Ph O-n-oc'cyl 4-CF3 5-Br H CH2Ph S:)CH2C02Et . :
35 4-CF3 H Me CH2Ph ~Et2 ., ,~:
.
:.:
," . : . . .. ~.'''.1 . .. :
ZC-OQ~65 Rl R2 B R8 Rg 4-CF35-Cl Me CH2Ph morpholino 4-CF35-~r Me CH2Ph 4-Cl-Ph 4-CF34-F Me CH2Ph Et 4-CF3 H CO2Me CH2Ph O-n-Bu ; 10 4-Cl H CO2Me CH2Ph O-iPr 4-~r H CO2Me CH2Ph OCH2CF3 4-OCF3 H CO2Me CH2Ph NMe2 4-CF35-Cl CO2Me CH2Ph piperidino 4-C15-Cl C02Me CH2Ph Ph 4-Br 5-Cl CO2Me CH2Ph 4-NO2-Ph 4-OCF35-Cl CO2Me CH2Ph Bu 4-CF35-Br CO2Me CH2Ph O-n-he~yl ; 4-C15-Br C02Me CH2Ph O-sec-Bu 4-Br 5-Br C02Me Q2ph OCH2CH20Et 4-OCF35-Br CO2Me CH2Ph NMe2 4-CF34-F CO2Me CH2Ph 2,6-di-Me-morpholino .: 4-C14-F CO2Me CH2Ph 3-Br-Ph 4-Br 4-F CO2Me CH2Ph 4-Me-Ph 4-OCF34-F CO2Me CH2Ph nPr i 25 4-CF35-CF3 CO2Me CH2Ph Me : 4-CF35-F CO2Me CH2Ph OEt 4-CF35-Cl Ph CH2Ph O-n-Bu 4-CF35-C14 Cl-Ph CH2Ph O-n-octyl 4-CF35-Cl C02Et CH2Ph OCH2ccl3 ~n .
'.
, ;2~)Q~65 ~aLl~_Z
N--N ~R, )7--N o S-N-S-Rg l S R,~ O
. :.
", '. :,.
,, - ,.:
Rl R2 B R8 Rg ::
;: 4-CF3 H CO2Me Me NMe2 4-Cl H CO2Me Me NMe2 .:i 4-Br H CO2Me Me NMe2 . - 25 4-OCF3 H CO2Me Me NMe2 4-CF3 5-Cl CO2Me Me NMe2 1; 4-Cl S-Cl CO2Me Me NMe2 ,` 9-Br 5-Cl CO2Me Me NMe2 4-OCF3 5-Cl CO2Me Me NMe2 :
304-CF3 5-Br CO2Me Me NMe2 9-C1 5-Br CO2Me Me NMe2 4-Br 5-Br CO2Me Me NMe2 .
` 4-OCF3 5-Br CO2Me Me NMe2 4-CF3 4-F CO2Me Me NMe2 ::
354-C1 4-F CO2Me Me NMe2 , :, ~
: ..
2~ 65 ~7 . Rl R2 9 R8 Rg 4-~r 4-F CO2Me Me NMe2 4-OCF34-F CO2Me Me NM~2 4-CF35-CF3 CO2Me Me NMe2 4-CF35-F CO2Me Me NMe2 4-CF35-Cl Ph Me NMe2 9-CF35-C14-Cl-Ph Me NMe2 : 4-CF35-Cl CO2Et Me NMe2 4-CF3 H CO2Me Me NEt2 4-Cl H CO2Me Me NEt2 4-Br H CO2Me Me NEt2 4-OCF3 H CO2Me Me NEt2 4-CF35-Cl CO2Me Me NEt2 9-C15-Cl co2Me Me NEt2 4-Br 5-Cl co2Me Me NEt2 4-OCF35-Cl CO2Me Me NEt2 4-CF35-Br CO2Me Me NEt2 4-C15-Br CO2Me Me NEt2 4-Br 5-Br CO2Me Me NEt2 4-OCF35-Br CO2Me Me NEt2 :~ 25 4-CF34-F CO2Me Me NEt2 4-C14-F CO2Me Me piperidino 4-Br 4-F CO2Me Me piperidino 4-OCF34-F CO2Me Me piperidino 4-CF35-CF3 CO2Me Me piperidino '~0 4-CF35-F CO2Me Me piperidino 4-CF35-Cl Ph Me piperidino 4-CF35-C14-Cl-Ph Me piperidino 4-CF35-Cl CO2Et Me piperidino 4-CF3 H CO2Me Me C2~5 4-CF35-Cl CO2Me Me C2H5 4-CF35-Br CO2Me Me C2H5 4-CF34-F CO2Me Me C2H5 .
. .
, ., . .
2C~ fiS
Rl R2 B R8 Rg 4-CF3 H C02Me Me n-he2cyl 4-Cl H C02Me Me n-he~yl 4-Br H C02Me Me n-he~yl .
4-OCF3 H CO2Me Me rl-hexyl 4-CF3 5-Cl CO2Me Me Ph 9-C1 5-Cl CO2Me Me Ph ~.
:: 4-Br 5-Cl CO2Me Me Ph 4-OCF3 5-Cl CO2Me Me Ph 4-CF3 5-EIr CO2Me Me 4-Cl-Ph 4-C1 5-Br CO2Me Me 4-Cl-Ph 4-Br 5-Br CO2Me Me 4-Cl-Ph 4-OCF3 5-Br CO2Me Me 4-Cl-Ph 4-CF3 4-F CO2Me Me 4-Me-Ph 4-C1 4-F CO2Me Me 4-Me-Ph 4-Br 4-F CO2Me Me 4-Me-Ph 4-OCF3 4-F CO2Me Me 4-Me-Ph 4-CF3 5-CF3 CO2Me Me n-Bu ~ 4-CF3 5-F CO2Me Me n-Bu ,; 4-CF3 S-Cl Ph Me n-Bu ;
. 25 4-CF3 5-C1 4-Cl-Ph Me n-Bu ~:
4-CF3 5-Cl CO2Et Me n-Bu 4-CF3 H H Et NMe2 .
4-CF3 5-Cl H Et NMe2 4-CF3 5-E~r H Et NMe2 4-CF3 4-F H Et NMe2 4-CF3 H Me Et NEt2 4-CF3 5-Cl Ne Et NEt2 4-CF3 5-Br Me Et NEt2 . 4-CF3 4-F Me Et NEt2 4-CF3 5-Cl CO2Me Et morpholino 4-C1 5-Cl CO2Me Et morpholino 4-Br 5-Cl CO2Me Et morpholino 4-OCF3 5-Cl CO2Me t morpholino ' , ',~
,' ' ,''.
. , . . :
2~?~Q~L65 , .
. :
1 R2 B R8 Rg 4-CF3 S-Cl CO2Me Et iPr 4~C1 5-Cl CO2Me Et iPr 4-Br 5-Cl CO2Me Et iPr 4-OCF3 5-Cl CO2Me Et iPr 4-CF3 5-Br C02Me Et n-Bu 4-C1 5-Br CO2Me Et n-Bu ; 4-Br 5-Br CO2Me Et n-Bu 4-OCF3 5-Br CO2Me Et n-Bu 4-CF3 4-F CO2Me Et Ph : 15 4-C1 4-F CO2Me Et Ph 4-Br 9-F CO2Me Et Ph 4-OCF3 4-F CO2Me Et Ph 4-CF3 H CO2Me iPr NMe2 4-Cl H CO2Me iPr NMe2 4-Br H CO2Me iPr NMe2 4-OCF3 H CO2Me iPr NMe2 4-CF3 5-Cl CO2Me iPr NMe2 ~ 4-C1 5-Cl CO2Me iPr NMe2 :
:.' 4-Br 5-Cl CO2Me iPr NMe2 ~: 25 4-OCF3 5-Cl CO2Me iPr NMe2 4-CF3 5-Br .CO2Me iPr NMe2 4-C1 5-Br CO2Me iPr NMe2 4-Br 5-Br CO2Me iPr NMe2 4-OCF3 5-Br CO2Me iPr NMe2 4-CF3 4-F CO2Me iPr NMe2 4-C1 4-F CO2~e iPr NMe2 4-Br 4-F CO2Me iPr NMe2 ' 4-OCF3 4-F CO2Me iPr NMe2 `I 4-CF3 5-CF3 CO2Me iPr NMe2 4-CF3 S-F CO2Me iPr NMe2 ' 4-CF3 5-Cl Ph iPr NMe2 4-CF3 5-C1 4-Cl-Ph iPr NMe2 4-CP3 5-Cl CO2Et iPr NMe2 , .
;
.. .
,, :
2(~ ''165 : .
Rl R2 ~ R8 Rg 4-CF3 H CO2Me iPr2, 6-di-Me-morpholino 4-CF35-Cl CO2Me iPr 2,6-di-Me-morpholino 4-CF35-Br CO2Me iPr 2,6-di-Me-morpholino 4-CF34-F CO2Me iPr 2,6-di-Me-morpholino 4-CF3 H CO2Me iPr piperidino : 4-OCF3 H CO2Me iPr piperidino 4-CF35-Cl CO2Me iPr Et 4-Cl S-Cl CO2Me iPr Et ~ 4-Br 5-Cl CO2Me iPr Et ~-: 15 4-OCF35-Cl CO2Me iPr Et 4 CF35 Br CO2Me iPr n-Bu 9-C15-Br CO2Me iPr n-Bu 4-Br 5-Br CO2Me iPr n-Bu 4-OCF35-Br CO2Me iPr n-Bu ~ 20 4-CF34-F CO2Me iPr . Ph ; q-Cl 9-F CO2Me iPr Ph ; 4-Br 4-F CO2Me iPr Ph 4-OCF34-F CO2Me iPr Ph 4-CF35-CF3 CO2Me iPr 4-Cl-Ph 4-CF35-F CO2Me iPr 4-Cl-Ph 4-CF35-Cl Ph iPr 4-Cl-Ph 4-CF35-C14-Cl-Ph iPr 4-Cl-Ph 4-CF35-Cl CO2Et iPr 4-Cl-Ph '.
~-., ~ .
-. .
~ .:
, , . . ~ , , .
., Table ~
.
-N-N
N
o 1 11 S-N-P-Y Rlo R~Y R1~
~ . .
: .
~- Rl R2 B R8 Y' Y'Rl~ Y Rll . . ._ ---- .
4-CF3 H CO2Me tBu S OEt OEt i 20 4-Cl H CO2Me tBu S OEt OEt ' 4-Br H CO2Me tBu S OEt OEt ~, 4-OCF3 H CO2Me tBu S OEt OEt .~ 4-CF3 5-Cl CO2Me tBu S OEt OEt ; 4-C1 5-Cl CO2Me tBu S OEt OEt ', 25 4-Br 5-Cl CO2Me tBu S OEt OEt , 4-OCF3 5-Cl CO2Me tBu S OEt OEt "~ 4-CF3 5-Br CO2Me tBu S OEt OEt . 4-C1 5-Br CO2Me tBu S OEt OEt 4-Br 5-8r CO2Me tBu S OEt OEt ` 3û 4-OCF3 5-Br CO2Me tBu S OEt OEt 4-CF3 4-F CO2Me tBu S OEt OEt 4-C1 4-F CO2Me tBu S OEt OEt . 4-Br 4-F CO2Me tBu S OEt OEt ;:. 4-OCF3 4-F CO2Me tBu S OEt OEt ~ 35 4-CF3 5-CF3 CO2Me tBu S OEt OEt :~ 4-CF3 5-F CO2Me tBu S OEt OEt 4-CF3 5-Cl Ph tBu S OEt OEt ,,, :.
.. . . . .
;. .;
., , , . . , ., . ;.: ,.. .: . .. : .:.. . .. :. . ~ .. ,, .. :. . ..... , . :
2~?U~65 ~ 62 . ,: .
.~ .
Rl R2 B R8 Y Y'Rlo Y Rll - .
., .
4-CF3 5-C1 4-Cl-Ph tBu S OEt OEt 4-CF3 5-Cl CO2Et t~u S OEt OEt 4-CF3 H CO2Me tBu S OCH2c(Me)2cH2O
4-Cl H CO2Me tBu S OCH2C(Me)2CH2O
4-Br H CO2Me tBu S OCH2C(Me)2CH2O
4-OCF3 H CO2Me tBu S OCH2c(Me)2cH2O
; 4-CF3 5-Cl CO2Me tBu S OCH2c(Me)2cH2O
4-C1 5-Cl CO2Me tBu S OCH2c(Me)2cH2O
~ 15 4-Br 5-Cl CO2Me tBu S OcH2c(Me)2cH2o " 4-OCF3 5-Cl CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me tBu S OCH2C(Me)2CH2O
: 4-C1 5-Br CO2Me tBu S OC~2C(Me)2CH2O
4-Br 5-Br CO2Me tBu S OCH2C(Me)2CH2O
; 20 4-OCF3 5-Br CO2Me tBu S OCH2C(Me)~CH2O
4-CF3 4-F CO2Me tBu S OCH2C(Me)2CH2O
. 4-C1 4-P CO2Me tBu S OCH2C(Me)2CH2O
4-Br 4-F CO2Me tBu S OCH2c(Me)2cH2O
.~ 4-OCF3 4-F CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 5-CF3 CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 S-F CO2Me tBu S OCH2C(Me)2CH2O
, 4-CF3 5-Cl Ph tBu S OCH2C(Me)2cH2o ' 4-CF3 5-C1 4-Cl-Ph tBu S OCH2C(Me)2CH2O
,~ 4-CF3 5-Cl CO2Et tBu S OCH2c(Me)2cH2O
4-CF3 H CO2Me tBu S OCH2CH2CH2O
: 4-C~ ~ C2~e tBu S OCH2CH2CH2O
4-~r H CO2Me tBu S OCH2CH2CH2O
4-OCF3 H CO2Me tBu S OCH2CH2C~2O
4-CF3 5-Cl C2~e tBu S OCH2cH2cH2O
4-C1 5-Cl CO2Me tBu S OcH2cH2cH2o 4-Br 5-Cl CO2Me tBu S OcH2cH2cH2o 4-OCF3 5-Cl CO2Me tBu S OcH2cH2cH2o ., ~A .
Z(~ 65 Rl R2 B RU Y Y'Rlo Y Rll 4-CF35-Br CO2Me tBu S OCH2CH2CH20 4-C1 5-Br CO2Me tBu S OCH2CH2CH20 4-Br 5-Br C02Me tBu S OCH2CH2CH20 4-OCF3 5-Br CO2Me tBu S OCH2CH2CH20 4-CF3 4-F CO2Me tBu S OCH2CH2CH20 4-C1 4-F CO2Me tBu S OCH2CH2CH20 4-Br 4-F CO2Me tBu S OCH2CH2CH20 4-OCF3 4-F CO2Me tBu S OCH2CH2CH20 4-CF3 5-CF3 CO2Me tBu S oCH2CH2CH20 4-CF3 5-F CO2Me tBu S OCH2CH2CH20 4-CF3 5-Cl Ph tBu S OCH2CH2CH20 4-CF35-~1 4-Cl-Ph tBu S OCH2CH2CH20 4-CF35-Cl C02Et tBu S OCH2Q2CH20 4 -CF3 H CO2Me tBu S CH2cH2 4-Cl H CO2Me tBu S OCH2CH20 :
4-Br H CO2Me tBu S OCH2CH2 . 4-OCF3 H CO2Me tBu S CH2cH2 4-CF3 5-Cl CO2Me tBu S CH2cH2 4-C1 5-Cl CO2Me tBu S CH2cH2 4-Br 5-Cl CO2Me tBu S CH2cH2 4-OCF3 5-Cl CO2Me tBu S OCH2CH20 4-CF3 5-Br C02Me tBu S CH2cH2 4-C1 5-Br CO2Me tBu S OCH2CH20 . 30 4-Br 5-Br CO2Me tBu S CH2cH2 4-OC~3 5-Br C02Me tBu S CH2cH2 !:~
4-CF3 4-F CO2Me tBu S CH2cH2 4-C1 4-F CO2Me tBu S CH2cH2 ~' 4-Br 4-F C02Me tBu S ~CH2cH2 9-OCF3 4-F CO2Me tBu S OCH2CH20 .
4-CF3 5-CF3 CO2Me tBu S CH2cH2 4-CF3 5-F C02Me tBu S OCH2CH20 : -' ..
.: ~ , ' .. . . : -: .. .
. :; :: ~. : ~
2~()Q'~65 Rl R2 B R8 Y Y'Rlo Y Rll 4-CF3 5-Cl Ph tBu S CH2cH2 4-CF3 5-C1 4-Cl-Ph tBu S OCH2CH2 4-CF3 5-Cl CO2Et t~u S OCH2 Q2 4-CF3 H CO2Me iPr S OEt OEt 4-Cl H CO2Me iPr S OEt OEt 4-8r H CO2Me iPr S OEt OEt 4-OCF3 H CO2Me iPr S OEt OEt .~ 4-CF3 5-Cl CO2Me iPr S OEt OEt 4-C1 5-Cl CO2Me iPr S OEt OEt 4-Br 5-Cl CO2Me iPr S OEt OEt 4-OCF3 5-Cl CO2Me iPr S OEt OEt 9-CF3 5-Br CO2Me iPr S OEt OEt 4-C1 5-Br CO2Me iPr S OEt OEt : 20 4-Br 5-Br CO2Me iPr S OEt OEt 4-OCP3 5-Br CO2Me iPr S OEt OEt 4-CF3 4-F CO2Me iPr S OEt OEt 4-C1 4-F CO2Me iPr S OEt OEt 4-Br 4-F CO2Me iPr S OEt OEt : 25 4-OCF3 4-F CO2Me iPr S OEt OEt :
4-CF3 5-CF3 CO2Me iPr S OEt OEt 4-CF3 5-F CO2Me iPr S OEt OEt 4-CF3 5-Cl Ph iPr S OEt OEt ~' 4-CF3 5-C1 4-Cl-Ph iPr S OEt OEt 4-CF3 5-Cl CO2Et iPr S OEt OEt 4-C~3 H CO2Me iPr S OCH2c(Me)2cH2O
4-Cl H CO2Me iPr S OCH2C(Me)2cH2o 4-~r H CO2Me iPr S OCH2C(Me)2cH2o 4-OCF3 H CO2Me iPr S OCH2C~Me)2cH2O
3S 4-CF3 5-Cl CO2Me iPr S OcH2c(Me)2cH2o 4-C1 5-Cl CO2Me iPr S OCH2C(Me)2cH2O
., "
''' ' '.
:- ' ~ : ~: . :
' '. ' ' . , . ' . : .
2~ 65 Rl R2 B R8 Y Y'Rlo Y'R
. ~.
4-13r 5-Cl C02Me iPr S OCH2C(Me)2CH20 4-OCF3 S-Cl CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me iPr S OCH2C(Me)2CH2O
:~ 10 4-C1 5-Br CO2Me iPr S OCH;~C(Me)2CH20 q-Br 5-Br CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 5-Br CO2Me iPr S OCH2c(Me)2cH2O
;~ 4-CF3 4-F CO2Me iPr S OCH2C~Me)2CH2O
4-Cl 9-F CO2Me iPr S OCH2C(Me)2CH2O
4-Br 4-F CO2Me iPr S OCH2C(Me)2CH2O
4-OCF3 4-F CO2Me iPr S OcH2c(Me)2cH2o 4-CF3 5-CF3 CO2Me iPr S - OCH2C(Me) 2CH2O
4-CF3 5-F CO2Me iPr S OCH2C(Me)2CH2O
4-CF3 5-Cl Ph iPr S OCH2c(Me)2cH2O
4-CF3 5-C1 4-Cl-Ph iPr S OCH2c(Me)2Q2O
4-CF3 5-Cl CO2Et iPr S OCH2c(Me)2cH2O
4-CF3 H CO2Me Me S OEt OEt 4-Cl H CO2Me Me S OEt OEt 4-Br H CO2Me Me S OEt OEt 4-OCF3 H CO2Me Me S OEt OEt . 4-CF3 S-Cl CO2Me Me S OEt OEt~i 4-Cl S-Cl CO2Me Me S OEt OEt :.`' 4-Br S-Cl CO2Me Me S OEt OEt 4-OCF3 S-Cl CO2Me Me S OEt OEt.
4-CF3 5-Br CO2Me Me S OEt OEt 4-C1 5-Br CO2Me Me S OEt OEt 4-Br 5-Br CO2Me Me S OEt OEt::.
;,. 4-OCF3 S-Br CO2Me Me S OEt OEt :
. 4-CF3 4-F CO2Me Me S OEt OEt 4-C1 4_~ CO2Me Me S OEt OEt ` 4-Br 4-F CO2Me Me S OEt OEt 4-OCF3 4-F CO2Me Me S OEt OEt 4-CF3 5-CF3 CO2Me Me . S OEt OEt ~,~, , , - ,:' .
" .
..
2~ 65 Rl R2 El R8 Y y'R10 Y Rll S
4-CF3 5-F CO2Me Me S OEt OEt 4-CF3 5-Cl Ph Me S OEt OEt 4-CF3 5-C1 4-Cl-Ph Me S OEt OEt 4-CF3 H CO2Me tBu O OEt OEt 4-Cl H CO2Me tBu O OEt OEt .; 4-~r H CO2Me tBu O OEt OEt 4-OCF3 H CO2Me tBu O OEt OEt ; 4-CF3 5-Cl CO2Me tBu O OEt OEt 4-C1 5-Cl CO2Me tBu O OEt OEt 4-Br 5-Cl CO2Me tBu O OEt OEt :
4-OCF3 5-Cl CO2Me tBu O OEt OEt 4-CF3 5-Br CO2Me tBu O OEt OEt 4-C1 5-Br CO2Me tBu O OEt OEt .
4-Br 5-Br CO2Me tBu O OEt OEt 4-OCF3 5-Br CO2Me tBu O OEt OEt 4-CF3 4-F CO2Me tBu O OEt OEt ~:; 4-C1 4-F CO2Me tBu O OEt OEt 4-Br 4-F CO2Me tBu O OEt OEt 4-OCF3 4-F CO2Me tBu O OEt OEt 4-CF3 5-CF3 CO;!tqe tBu O OEt OEt ..
4-CF3 5-F CO2Me tBu O OEt OEt 9-CF3 S-Cl Ph tBu O OEt OEt 4-CF3 5-C1 4-Cl-Ph tBu O OEt OEt 4-CF3 5-Cl CO2Et tBu O OE:t OEt 4-CF3 ~3 CO2Me tBu O OCH2C(Me)2CH20 4-Cl H CO2Me tBu O OCH2C(Me)2cH2o 4-Br H C02Me tl3u o .0CH2C(Me)2CH20 4-OCF3 H CO2Me tBu O OCH2C(Me)2cH2o 4-CF3 5-Cl CO2Me tBu O OCH2C(Me)2cH2o 4-C1 5-Cl CO2Me tE~u O OCH2C(Me)2cH2 ... .
,~
, ~ .
;i .
2~Q~65 Rl R2 B R8 Y Y'Rlo Y R
4-Br 5-Cl CO2Me tBu O OCH2C(Me)2CH2O
4-OCF3 5-CI CO2Me tBu O OCH2C(Me)2CH2O
4-CF3 5-Br CO2Me tBu O OCH2C(Me)2cH2o 4-C1 5-Br CO2Me tBu O OCH2C(Me)2CH2O
4-Br S-Br CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 S-Br CO2Me tBu O OCH2C(Me)2cH2o 4-CF3 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-C1 4-F CO2Me tBu O OCH2C(Me)2CH2O
: 15 4-Br 4-F CO2Me tBu O OCH2C(Me)2cH2o 4-OCF3 4-F CO2Me tBu O OCH2C(Me)2cH2o :~ 4-CF3 5-CF3 CO2Me tBu O OCH2C(Me)2Q 2o 4-CF3 5-F CO2Me tBu O OCH2C(Me)2CH2O
4-CF3 5-Cl Ph tBu O OCH2C(Me)2CH2O
4-CF3 5-C1 4-Cl-Ph tBu O OCH2C(Me)2cH2o . 4-CF3 5-Cl CO2Et tBu O OCH2C(Me)2cH2o :
~' .
,, ~ 3C
~ .
;:~ , ......
~`"
. ~.
. .~, .
. ~ . . . , . . . . .. .- . : . . . .
2C~G~65 6~
Table 4 .
N-~ ~ R~
~, ,Y, S-N-P-Y R
- 15 l l R R
, !
Rl R2 B R8 Y Rlo Y ~11 . -..
4-CF3 H CO2Me iPr O Et OEt ,i, 4-Cl H CO2Me iPr O Et OEt ~;, 25 4-Br H CO2Me iPr O Et OEt 4-OCF3 H CO2Me iPr O Et OEt 4-CF3 5-Cl CO2Me iPr O Et OEt , 9-C1 5-Cl CO2Me iPr O Et OEt ; 4-Br 5-Cl CO2Me iPr O Et OEt ` 30 9-OCF3 5-Cl CO2Me iPr O Et OEt , 4-CF3 5-Br CO2Me iPr O Et OEt 4-C1 5-~r CO2Me iPr O Et OEt 4-Br 5-Br CO2Me iPr O Et OEt 1 4-OCF3 5-Br CO2Me iPr O Et OEt - 35 4-CF3 4-F CO2Me iPr O Et OEt ,.. .
/~
2C~ ÇiS
Rl R2 B R8 Y' Rlo Y Rll :
` 4-C14-F CO2Me iPr O Et OEt 4-Br 4-F CO2Me iPr O Et OEt 4-OCF34-F CO2Me iPr O Et OEt ! :
4-CF35-CF3 CO2Me iPr O Et OEt 4-CF35-F CO2Me iPr O Et OEt 4-CF35-Cl Ph iPr O Et OEt 4-CF35-C14-Cl-Ph iPr O Et OEt 4-CF35-Cl CO2Et iPr O Et OEt 4-CF3 H CO2Me iPr O Et O-iPr ; 15 4-Cl H CO2Me iPr O Et O-iPr . 4-Br H CO2Me iPr O Et O-iPr 4-OCF3 H CO2Me iPr O Et O-iPr ;, 4-CF35-Cl CO2Me iPr O Et O-iPr 4-C15-Cl CO2Me iPr O Et O-iPr 4-Br 5-Cl CO2Me iPr O Et O-iPr 4-OCF35-Cl CO2Me iPr O Et O-iPr . 4-CF35-Br CO2Me iPr O Et O-iPr .. 4-Cl S-Br CO2Me iPr O Et O-iPr ,~ 4-Br 5-Br CO2Me iPr O Et O-iPr 4-OCF35-Br CO2Me iPr O Et O-iPr 4-CF34-F CO2Me iPr O Et O-iPr ~ .
~; 4-C14-F CO2Me iPr O Et O-iPr 4-Br 4-F CO2Me iPr O Et O-iPr ~ i~.
4-OCF34-F CO2Me iPr O Et O-iPr i~.
`- 30 4-CF35-CF3 CO2Me iPr O Et O-iPr ~, : 4-CF35-F CO2Me iPr O Et O-iPr `~
4-CF35-Cl Ph iPr O Et O-iPr . 4-CF35-C14-Cl-Ph iPr O Et O-iPr 4-CF35-Cl CO2Et iPr O Et O-iPr 4-CF3 H CO2Me iPr O Et OPh -4-Cl H CO2Me iPr O Et OPh "
.,: .. : .. -: - . , ..... .. . . , . -. . .: , . .. , . ., . ,, ~
! ~ . ' -, . . . . , " . .. . . , , , '~ . . . , ' . ., . ' . ,, : .. , . ' . .: , .
~, . . .. .. . . . . .
2~(~C~L65 . Rl R2 B R8 Y' Rlo Y R
_ 4-Br H CO2Me iPr O Et OPh 4-OCF3 H CO2Me iPr O Et OPh : 9-CF35-Cl CO2Me iPr O Et OPh 4-C15-Cl CO2Me iPr O Et OPh 4-Br 5-Cl CO2Me iPr O Et OPh 4-OCF35-Cl CO2Me iPr O Et OPh 4-CF35-~r CO2Me iPr O Et OPh 4-C15-Br CO2Me iPr O Et OPh 4-Br 5-Br CO2Me iPr O Et OPh 4-OCF35-Br CO2Me iPr O Et OPh ; 4-CF34-F CO2Me iPr O Et OPh 4-C14-F CO2Me iPr O Et OPh .. 4-Br 4-F CO2Me iPr O Et OPh 4-OCF34-F CO2Me iPr O Et OPh 4-cF35-cF3 co2Me iPr O Et OPh 4-CF35-F CO2Ne iPr O Et OPh `. 4-CF35-Cl Ph iPr O Et OPh 4-CF35-C14-Cl-Ph iPr O Et OPh 4-CF35-Cl CO2Et iPr O Et OPh 4-Br 4-F CO2Me iPr O Ph OEt 4-OCF34-F CO2Me iPr O Ph OEt ~` 4-CF35-CF3 CO2Me iPr O Ph OEt 4-CF35-F . CO2Me iPr O Ph OEt 4-CF35-Cl Ph iPr O Ph OEt .~ 30 4-CF35-C19-Cl-Ph iPr O Ph OEt 4-CF35-Cl CO2Et iPr O Ph OEt . 4-CF3 H CO2Me tBu O Et OEt 4-Cl H CO2Me tBu O Et OEt : 4-Br H CO2Me tau O Et OEt :' 35 4-OCF3 H CO2Me tBu O Et OEt .~ 4-CF35-Cl CO2Me tBu O Et OEt 4-C15-Cl CO2Me tBu O Et OEt ,.
~:
~Q~65 :
Rl R2 B R8 Y' Rlo Y R
4-Br 5-Cl CO2Me tBu O Et OEt 4-OCF3 S-Cl CO2Me tBu O Et OEt 4-CF35-Br CO2Me tBu O Et OEt 4-Cl S-Br CO2Me tBu O Et OEt 4-Br 5-Br CO2Me tBu O Et OEt 4-OCF35-Br CO~Me tBu O Et - OEt 4-CF34-F CO2Me tBu O Et OEt 4-C1 4-F CO2Me t~u O Et OEt 4-Br 4-F CO2Me tBu O Et OEt 4-OCF34-F CO2Me tBu O Et OEt 4-CF3 5-CF3 CO2Me tBu O Et OEt 4-CF3 5-F CO2Me tBu O Et OEt 4-CF3 5-Cl Ph tBu O Et OEt ~;
4-CF3 5-C1 4-Cl-Ph tBu O Et OEt 4-CF3 5-Cl C02Et tBu O Et OEt ~
4-CF3 H CO2Me tBu O Et O-iPr ~ ~;:
4-Cl H CO2Me tBu O Et O-iPr -Br H CO2Me tBu O Et O-iPr 4-OCF3 H CO2Me tBu O Et O-iPr 4-CF35-Cl CO2Me tBu O Et o-iPr 4-C1 5-Cl CO2Me tBu O Et O-iPr 4-Br 5-Cl CO2Me tBu O Et O-iPr 4-OCF35-Cl CO2Me tBu o Et O-iPr 4-CF35-Br CO2Me tBu O Et O-iPr . 30 Cl 5-Elr C02Me tBu O Et O-iPr 4-Br 5-Br CO2Me tBu O Et O-iPr :
: 4-OCF35-Br CO2Me tBu O Et O-iPr 4-CF34-F CO2Me tBu O Et O-iPr 4-C1 4-F C02Me tElu O Et O-iPr 3~ 4-Br 4-F CO2Me tE~u o Et O-iPr . 4-OCF34-F CO2Me tBu O Et O-iPr ;
4-CF35-CF3 CO2Me tBu o Et O-iPr 4-CF35-F CO2Me tBu O Et O-iPr ;
: ':
.
2~Q~I~S
Rl R2 B R8 Y' Rlo Y R
- 4-CF3 5-Cl Ph tBu O Et O-iPr 4-CF3 5-C1 4-Cl-Ph tBu O Et O-iPr 4-CF3 5-Cl CO2Et tBu O Et O-iPr 4-CF3 H CO2Me tBu S Et OPh 4-Cl H CO2Me tBu S Ph OEt 4-Br H CO2Me t9u S Ph O-iPr 4-OCF3 H CO2Me tBu S Ph OPh 4-Br 5-Br CO2Me iPr S iPr OEt 4-OCF3 5-Br CO2Me iPr S iPr O-iPr 4-CF3 4-F CO2Me iPr S iPr OPh 4-C1 4-F CO2Me iPr S nPr OEt 9-Br 4-F CO2Me iPr S nPr O-iPr 4-OCF3 4-F CO2Me iPr S nPr OPh 4-CF3 5-CF3 CO2Me tBu S Me OEt 4-CF3 5-F CO2Me tBu S Me O-iPr 4-CF3 5-Cl Ph tBu S Me OPh , .
` 4-CF3 5-C1 4-Cl-Ph tBu S Me O-sec-8u 4-CF3 5-Cl CO2Et tBu S Me O-nPr ,~, .
i 25 , i .
.~
:, , .- .. .. . . ..
2~ L65 :.
able 5 . . .
~: 4 ~ .
. ~
f ' .
,'', , . Rl R2 El Rlo R
~ 4-CF3 H CO2Me Et Et ., 4-Cl H CO2Me Et Et 4-Br H C2Me Et Et 4-OCF3 H CO2Me Et Et ~, 4-CF3 5-Cl CO2Me Et Et 4-Cl S-Cl CO2Me Et Et .1 4-Br 5-CI CO2Me Et Et i' 4-OCF3 S-Cl CO2Me Et Et ~ 30 4-CF3 5-Br CO2Me Et Et .~ 4-C1 5-Br CO2Me Et Et ~ 4-Br 5-Br CO2Me Et Et :i 4-OCF3 5-9r CO2Me Et Et .i 4-CF3 4-F CO2Me Et Et .~ .
~..
: . .
'7 .~., 2~!0Q~65 Rl R2 El Rlo Rll 4-C1 4-F CO2Me Et Et 4-Br 4-F CO2Me Et Et 4-OCF3 4-F CO2Me Et Et 4-CF3 5-CF3 CO2Me Et Et 4-CF3 S-F C~2Me Et Et 4-CF3 5-Cl Ph Et Et 4-CF3 5-C1 4-Cl-Ph Ft Et 4-CF3 5-Cl CO2Et Et Et Ç-CF3 5-Cl Ph Ph Ph 4-CF3 5-C1 4-Cl-Ph Ph Ph 4-CF3 5-Cl C2Et Ph Ph . ..
.. ,,, , , , - , ... .. .
.:, . , - . . :. . ..
2~Q~65 .
T~ble 6 N-N ~ R~
~ N :
O S-N-R~
lS
Rl R2 B R8 R12 .
: ' 4-CF3 H CO2Me nBu nBu ':
4-Cl H CO2Me nBu nBu 4-Br H CO2Me nBu nBu 4-OCF3 H CO2Me nBu nBu 4-CF3 5-Cl CO2Me nBu nBu 4-C1 5-Cl CO2Me nBu nBu 4-Br 5-Cl CO2Me nBu nBu 4-OCF3 5-Cl CO2Me nBu nBu 4-CF3 5-Br CO2Me nBu nBu 4-C1 5-Br CO2Me ~Bu DBu ~
4-Br 5-Br CO2Me nBu nBu :, 4-OCF3 5-Br CO2Me nBu nBu 4-CF3 4-F CO2Me nBu nBu : ~ : ... :: :-- .. . - . . . .. ..
- ~ /
2(~Q~L6S
Rl R2 El R8 R12 4-C14-F CO2Me ~Bu nBu 4-Br 4-F CO2Me nSu ~B~
4-QCF34-F CO2Me nBu nBu 4-CF35-CF3 CO2Me nBu nBu 4-CF35-F CO2Me ~Bu ~Bu 4-CF35-Cl Ph nBu n9u 4-CF35-C14-Cl-Ph n8u nBu 4-CF35-Cl CO2E~ nBu nBu 4-CF3 H CO2Me -CH2CH2CH2cH2cH2-4-Cl H CO2Me -CH2CH2CH2cH2cH2-4-Br H CO2Me -CH2CH2CHzcH2cH2~
4-OCF3 H CO2Me -CH2CH2CH2cH2cH2-4-CF35-Cl CO2Me -CH2CH2CH2cH2cH2-4-C15-Cl co2Me -CH2CH2CH2cH2cH2-4-Br 5-Cl co2Me -CH2CH2CH2c~2cH2-4-OCF35-Cl C02Me -CH2CH2~HzCH2cH2 4-CF35-Br CO2Me -CH2CH2CH2cH2cH2-4-C15-Br CO2Me -CH2CH2CH2cH2cH2-4-Br 5-Br CO2Me -CH2CH2CH2cH2cH2-40CF35-8r CO2Me -CN2CH2CH2cH2cH2-4-SF34-F CO2Me -CH2CH2CH2cH2cH2-4-C14-F ~02Me -CH2CH2CH2cH2cH2-4-Br 4-F C02Me -CH2CH2CH2cH2cH2-4-OCF34-F CO2Me -CH2CH2CH2cH2cH2-0 4-CF35-CF3 CO2Me -CH2CH2CH2cH2cH2-4-CF35 F CO2Me -CH2CH2CH2cN2cH2-4-C~35-Cl Ph -CH2CH2CH2cH2cH2-4-~F35-C1 4-Cl-Ph -CH2CH2CH2CH2CH2-4-CF35-Cl C02Et -CH2CH2CH2cH2c~2-4-C~3 H CO2Me -CH2CH20CH2cH2-4-Cl H CO2Me -CH2CH20CH2CH2- ~ :
4-Br H CO2Me -CH2CH20CH2CH2-.
2~ L65 4-OCF3 H CO2Me -CH2CH20cH2cH2-4 CF3 5-Cl CO2Me -CH2CH20CH2CH2-4-C1 5-Cl C02Me -CH2cH20cH2Q2 4-Br 5-Cl C2Me -CHzCH2ClCH2CH2 4-OCF3 5-Cl CO2Me _CH2CH20CH2cH2-4-CF3 5-Br CO2Me -CH2CH20CH2cH2 4-C1 5-Br CO2Me -CHzCH20CH2CH2-4-Br 5-Br COzMe -CH2CH20CH2cH2 4-OCF3 5-Br CO2Me -CH2CH20CH2cH2-4-CF3 4-F CO2Me -CH2CH20CH2cH2-4-C1 4-F CO2Me -CH2CH20CH2CH2 4-Br 4-F CO2Me -CH2CH20CH2cH2-4-OCF3 4-F CO2Me -CH2CH20CH2CH2~
4-CP3 5-CF3 CO2Me -CH2CH20CH2cH2-2 0 4-CF3 5-F CO2Me -CH2CH20CH2cH2-4-CF3 5-Cl Ph -CH2CH20CH2cH2 4-CF3 5-C1 4-Cl-Ph -CH2CH20CH2CH2-4-CF3 5-Cl C02Et -CH2CH2~CH2cH2-4-CF3 H CO2Me -CH2CHMeOCHMeCH2-2 5 4-Cl H C02Me -CHzCHMeOCHMeCH2-4-Br H C02Me -CH2CHMeOCHMeCH2-4-OCF3 H CO2Me -CH2CHMeOCHMeCH2-4-CF3 5-C~ C~2Me -C1~2CHMeOCHMeCH2-4-C1 5-~1 ~2M~ -CH2CHMeOCHMeCN2-3 0 4-Br 5-Cl CO2Me -CH2CHMeOCHMeCH2-4-OCF3 S-Cl CO2Me -CH2CHMeOCHMeCH2-4-CF3 5-Br CO2Me -CH2CHMeOCHMeCH2-4-C1 5-Br CO2Me -CH2CHMeOCHMeCH2-4-~r 5-Br C02Me -CH2CNMeOCHMeCH2 3 5 4-OCF3 5-Br CO2Me -CH2CHMeOCHMeCH2-4-CF3 4-F CO2Me -CH2CNMeOCHMeCH2-. .
2~0Q~65 . Rl R2 B RB R12 4-C14-F C~2Me -cH2cHMeoc~ecH2 4-Br 4-F C02Me -CH2CE~eOC}~eCH2-4-OCF34-F C02M~ -cH2cHMeoc~lMec~2 4-CF35-CF3 CO2Me -CH2CHMeOCHMeCH2-4 CF35 F C02Me -CH2C8MeOCHMeCH2-4-CF35-Cl Ph -CH2CHMeOCHMeCH2-4 CF35 cl 4-Cl-Ph -CH2C~MeOCHMeCH2-4-CF35-Cl CO2Et -CH2CHMeOCHMeCH2-4-CF3 N CO2Me Et c 4-Cl H CO2Me Et cyclo-C6H
4-Br H C02Me Et cYClo-C6H
4-OCF3 H CO2Me Et cyclo-C6H
4-CF35-Cl CO2Me Et cyclo-C
4-C15-Cl co2Me Et c 4-Br 5-Cl C02Me Et cyclo-C6H
4-OCF35-Cl CO2Me Et cyclo-C6H
4-CF35-8r CO2Me Et CYC1-4-C15-Br CO2Me Et c 4-Br 5-Br CO2Me Et Cyclo-c6H
4-OCF35-Br CO2Me Et c 4-CF34-F CO2Me Et c 4-C14-F CO2Me St cyclo-C6H
4-Er 4-F CO2Me Et c 4-OCF34-~ CO2Me Et cyclo-c6Hll q-CF35-CF3 C~2Me Et CYC1~C6Hll . .
4-CF35-F CO2Me Et c 4-CF35-Cl Ph Et c 4-CF35-C14-Cl-Ph Et Cyclo-C6H
4-CF35-Cl C02Et Et Cyclo-c6Hll 4-CF3 H CO2Me iPr CH2CH2C2Et 4-Cl H CO2Me iPr CH2CH2C2Et 4-Br H CO2Me iPr CH2CH2C2Et 2~C~Q~65 -4-OCF3 H CO2Me iPr CH2CH2C2Et 4-CF3 5-ClCO2Me iPr CN2CH2C02Et 4-C1 5-ClCO2Me iPr CH2CH2C2Et 4-Br 5-Cl C~2Me iPr CH2CH2C2Et 4-OCF3 5-CI COzMe iPr C~2CH2C2Et 4 CF3 5 Br C02Me iPr CH2C~2C2Et 4-C1 5-Br C~2Me iPr CH2CH2C2Et 4-Br 5-Br CO2Me iPr CN2CH2C2Et 4-OCF3 5-BrC2Me iPr CH2CH2C2Et 4 CF3 4 FC02Me iPr CH2CH2CO2Et 4-C1 4-FCO2Me iPr CH2CH2C2Et 4-Br 4-FCO2Me iPr CH2CH2C2Et 4-OCF3 4-FCO2Me iPr CH2CH2C02Et 4-CF3 5-CF3CO2Me iPr CH2CH2CO2Et 4-CF3 5-FCO2Ne iPr CH2CB2CO2Et 4-C~3 5-Cl Ph iPr CH2CH2CO2Et 4-CF3 5-C1 4-Cl-Ph iPr CH2CH2~02Et 4-CF3 S-Cl CO2Et iPr CH2CH2C2Et 3n '' ' ' . ' ' ' ' ~\
2~ 6S
~bl~
N-N
Rl R2 B Rlo :
4-CF3 H CO2Me tBu 4-Cl H CO2Me tBu 4-Br H CO2Me tBu 25 4-OCF3 H CO2Me tBu 4-CF3 S-Cl CO2Me tBu 4-C1 5-CI CO2Me tBu 4-Br 5-Cl CO2Me tBu 4-OCF3 5-Cl CO2Me tBu 30 4-CF3 5-Br CO2Me tBu 4-C1 5-Br CO2Me tBu 4-9~ 5-Br CO2Me tBu 4-OCF3 5-Br CO2Me tBu 4-CF3 4-F CO2Me : tBu .~.
35 4-C1 4-F CO2Me tBu .
- - . , . : - . . ~ . :: : . : :: . : . . : : : . - - : . :: ::
2C~Q~65 Rl R2 Rlo '' 4-Br 4-F CO2Me tBu 4-OCF3 4-F CO2Me tBu 4-CF3 5-CF~ CO2Me tBu 4-CF3 5-F CO2Me tBu 4-CF3 5-Cl Ph tBu 4-CF3 5-C1 4-Cl-Ph tBu 4-CF3 S-Cl CO2St tBu 4-CF3 H CO2Me Ph 4-Cl H CO2Me Ph 4-Br H C02Me Ph 4-OCF3 H CO2Me Ph 4-CF3 5-Cl CO2Ne Ph 4-C1 5-Cl CO2Me Ph 4-Br 5-Cl CO2Me Ph 4-OCF3 5-Cl CO2Me Ph 4-CF3 5-~r CO2Me Ph 4-C1 5-Br CO2Me Ph 4-Br 5-Br CO2Me Ph 4-OCF3 5-Br CO2Me Ph 4-CF3 4-F CO2Me Ph 4-C1 4-F CO2Me Ph 4-9r 4-F CO2Me Ph 4-OCF3 4-F CO2Me Ph 4-CF3 5-CF3 CO2Me Ph 4-CF3 5-F CO2Me Ph 4-CF3 5-C~ Ph Ph . ,~
4-CF3 5-Cl 4-Cl-Ph Ph ';
4-CF3 5-Cl C2~t Ph 4-CF3 H CO2Me 4-Cl-Ph 4-Cl H CO2Me 4-Cl-Ph 4-Br H CO2Me 4-Cl-Ph .. - :: ,, . ' ,' : . . ,,. .: ::
Rl R2 B Rlo 4-OCF3 H CO2Me 4-Cl-Ph 4-CF3 5-Cl CO2Me q-Cl-Ph 4-C1 5-Cl CO2Me 4-Cl-Ph 4-Br 5-Cl CO2Me 4-Cl-Ph 4-OCF3 5-Cl CO2Me 4-Cl-Ph 4-CF3 5-Br CO2Me 4-Cl-Ph 4-C1 5-Br CO2Me 4-Cl-Ph 4-Br 5-Br CO2Me 4-Cl-Ph 4-OCF3 5-Br C02Me 4-Cl-Ph 4-CF3 4-F CO2Me 4-Cl-Ph 4-C1 4-F CO2Me 4-Cl-Ph 4-Br 4-F CO2Me 4-Cl-Ph 4-OCF3 4-F CO2Me 4-Cl-Ph 4-CF3 S-CF3 CO2Me 4-Cl-Ph 4-CF3 S-F CO2Me 4-Cl-Ph - : ., . . , . , . . ; . . ... . -. .~ , . . ~ ,, , . , ... ,, . , . ; - :
. .. .. . .. .. . . . . ..
2C~0~65 Table 8 10 ~ N-N
~ N
S -N
R~
Rl R2 B V R8 Rg 4-CF3 5-Br H O Me OEt 4-Cl S-Br H O Me OEt 4-Br 5-Br H O Me OEt 4-OCF3 S-Br H O Me OEt 4-CF3 5-Cl H O Me OEt 4-C1 5-Cl H O Me OEt 4-Br 5-Cl H O Me OEt 4-CF3 5-CF3 H O Me OEt 4-CF3 4-F H O Me OEt 4-CF3 H H O Me OEt 4-CF3 S-Br CO2Me O Me OEt 4-CF3 5-Cl CO2Me O Me OEt 4-CF3 5-CF3 CO2Me O Me OEt 4-CF3 4-F CO2Me O Me OEt 2~ 6S
Rl R2 B V RB Rg -4-CF3 H CO2Me Me OEt 4-CF35-Cl H S Me OEt 4-C15-Cl H S Me OEt 4-Br 5-CI H S Me OEt lD 4-CF35-Br N S Me OEt 4-CF35-F H S Me OEt 4-CF34-Cl H S Me OEt 4-CF34-F H S Me OEt 4-CF3 H H S Me OEt 4-CF35-Cl CO2Me S Me OEt 4-CF35-Br CO2Me S Me OEt 4-CF35-F CO2Me S Me OEt 4-CF39-Cl CO2Me S Me OEt 4-CF34-F CO2Me S Me OEt 4-CF3 H CO2Me S Me OEt 4-CF35-Br H O Me O-n-Bu 4-C15-Br H O Me O-n-Bu 4-Br 5-Br H O Me O-n-Bu 4-OCF35-Br H O Me O-n-Bu 4-CF35-Cl H O Me O-n-Bu 4-C15-Cl H O Me O-n-Bu 4-Br S-Cl H O Ne O-n-Bu 4-CF35-CF3 H O Me O-n-Bu 4-CF34-F H O Me O-n-Bu 4-CF3 H H O Me O-n-Bu 4-CF35-Br CO2Me O Me O-n-Bu 4-CF35-Cl CO2Me O Me O-n-Bu 4-CF35-CF3 CO2Me O Me O-~-Bu 4-CF34-F CO2Me O Me O-n-Bu 4-CF3 H CO2Me Me O-n-Bu 4-CF35-Cl H S Me O-n-Bu 4-C15-Cl H S Me O-n-Bu 2~ 65 Rl R2 B V RB R9 4-8r 5-Cl H S Me O-D-Bu 4-CF35-Br H S Me O-n-Bu 4-CF35-F H S Me O-n-Bu 4-CF34-Cl H S Me O-n-9u 4-CF34-F H S Me O-n-Bu 4-CF3 H H S Me O-D-Bu 4-CF35-Cl CO2Me S Me O-n-Bu 4-CF35-Br CO2Me S Me O-n-Bu 4 CF35 F CO2Me ~ Me O-D-Bu 4-CF34-Cl CO2Me S Me O-n-Bu 4-CF34-F CO2Me S Me O-n-Bu 4-CF3 H CO2Me S Me O-n-Bu 4-CF35-Br H O Me O-n-hexyl 4-C15-Br H O Me O-n-hexyl 4-Br S-Br H O Me O-n-hexyl 4-OCF35-Br H O Me O-n-he~yl 4-CF35-Cl H O Me O-n-hexyl 4-C15-Cl H O Me O-n-hexyl 4-Br 5-Cl H O Me O-n-he~yl 4-CF35-CF3 H O Me O-n-he~yl 4-CF34-F H O Me O-D-he~yl 4-CF3 H H O Me O-n-hexyl 4-CF35-Br CO2Me O Me O-n-he~yl 4-CF35-Cl CO2Me O Me O-n-he~yl 3~ 4~CF35-cF3 CO2Me O Me O-n-he~yl 4-CF34-F CO2Me Me O-n-he~yl 4-CF3 H CO2Me Me O-~-he~yl 4-CF35-Cl H S Me O-n-he~yl 4-C15-Cl H S Me O-n-he~yl 4-Br 5-Cl H S Me O-n-he~yl 4-CF35-Br H S Me O-n-hexyl 4-CF35-F H S Me O-n-he~yl .: ~ . :
: . : -2~ 6S
~6 Rl R2 i3 V RB Rg 4-CF34-Cl H S Me O-n-~exyl 4-CF34-F N S Me O-n-he~yl 4-CF3 H ~ S Me O-n-he~yl 4-CF35-Cl CO2Me S ~e O-n-he~yl 4-CF35-Br CO2Me S Me O-n-hexyl 4-CF35-F CO2Me S Me O-n-hexyl 4-CF34-Cl CO2Me S Me O-n-heryl 4-CF34-F CO2Me S Me O-n-he~yl 4-CF3 H CO2Me S Me O-n-hexyl 4-CF35-Br H O Me O-n-octyl 4-C15-Br H O Me O-n-octyl 4-Br 5-Br H O Me O-n-octyl 4-OCF35-9r H O Me O-n-octyl 4-CF35-Cl H O Me O-n-octyl 4-C15-Cl H O Me O-n-octyl 4-Br 5-Cl H O Me O-n-octyl 4-CF35-CF3 H O Me O-n-octyl 4-CF34-F H O Me O-n-octyl 4-CF3 H H O Me O-n-octyl 4-CF35-Br CO2Me O Me O-n-octyl 4-CF35-Cl CO2Me O Me O-n-octyl 4-CF35-CF3 CO2Me O Me O-n-octyl 4-CF34-F CO2Me O Me O-n-octyl 4-CF3 H CO2Me Me O-n-octyl 4-CF35-CI N S Me O-n-octyl 4-C15-Cl H S Me O-n-octyl 4-Br 5-Cl H S Me O-n-octyl 4-CF35-Br H S Me O-n-octyl 4-CF35-F H S Me O-n-octyl 4-CF34-Cl H S Me O-n-octyl 4-CF34-F H S Me O-n-octyl 4-CF3 H N S Me O-n-octyl .
. . .
' , . . , ~. : - . : . : ~ . ~ - : .
.: .. , . . , . . , ~.. , :.. .... . , : :
Z~ 65 Rl R2 ~ V R8 R9 4-CF35-Cl CO2Me S Me O-n-~ctyl 4-CF35-~r CO2Me S Me O-n-octyl 4 CF35 F C2Me S Me O-n-octyl 4-CF34-Cl CO2Me S Me O-D-~tyl 4 CF34 F C2Me S Me O-n-octyl 4-CF3 H CO2Me S Me O-n-octyl 4-CF35-Br H O Me O-n-decyl 4-C35-Br H O Me O-n-decyl ~-Br 5-Br H O Me O-n-decyl 4-OCF35-Br H O Me O-n-decyl 4-CF35-Cl H O Me O-n-decyl 4-C15-Cl H O Me O-n-decyl 4-Br 5-Cl H O Me O-n-decyl 4-CF35-CF3 H O Me O-n-decyl 2~ 4-CF34-F H O Me O-n-decyl 4-CF3 H H O Me O-n-decyl 4-CF35-Br CO2Me O Me O-n-decyl 4-CF35-Cl CO2Me O Me O-n-decyl Ç-CF35-CF3 CO2Me O Me O-n-decyl ~ 25 4-CF34-F CO2Me Me O-n-decyl 4-CF3 H CO2M.e O Me O-n-decyl 4-CF35-Cl H S Me O-n-decyl 4-C15-Cl H S Me O-n-decyl 4-~r 5-Cl H S Me O-n-decyl 4-CF35-~r H S Me O-n-decyl 4-CF35-F H S Me O-n-decyl 4-C~34-Cl H S Me O-n-decyl 4-CF34-F H S Me O-n-decyl 4-CF3 H H S Me O-n-decyl 4-CF35-Cl CO2Me S Me O-D-decyl 4-CF35-Br CO2Me S Me O-n-decyl 4-CF35-F CO2Me S Me O-n-decyl 4-CF34-Cl CO2Me S Me O-n-decyl 2~Q~65 , Rl R2 B V R8 Rg 4-CF34-F CO2Me S Me O-r-decyl 4-CF3 H CO2Me S Me O-~-aecyl 4-CF35-Br H O Me O-n-dodecyl 4-C15-Br H O Me O-n-dodecyl 4-8r S-Br H O Me O-n-dodecyl 4-OCF35-8r H O Me O-n-dodecyl 4-CF35-Cl H O Me O-n-dodecyl 4-C15-Cl N O Me O-n-dodecyl 4-8r 5-Cl H O Me O-n-dodecyl 4-CF35-CF3 H o Me O-n-dodecyl 4-CF34-F H O Me O-n-dodecyl 4-CF3 H H O Me O-n-dodecyl 4-CF35-8r CO2Me O Me O-n-dodecyl 4-CF35-Cl CO2Me O Me O-n-dodecyl 4-CF35-CF3 CO2Me O Me O-n-dodecyl 4-CF34-F CO2Me O Me O-n-dodecyl 4-CF3 H CO2Me O Me O-n-dodecyl 4-CF35-Cl H S Me O-n-dodecyl 4-C15-Cl H S Me O-n-dodecyl 4-8r 5-Cl H S Me O-n-dodecyl 4-CF35-Br H S Me O-n-dodecyl 4-CF35-F H S Me O-n-dodecyl 4-CF34-Cl H S Me O-n-dodecyl 4-CF34-F H S Me O-n-dodecyl 4-CF3 H H S Me O-n-dodecyl 4-CF35-Cl CO2Me S Me O-n-dodecyl 4-CF35-Br CO2Me S Me O-n-dodecyl 4-CF35-F CO2Me S Me O-n-dodecyl 4-CF34-Cl CO2Me S Me O-n-dodecyl 3~ 4-CF34-F CO2Me S Me O-n-dodecyl ~.:.: .. -: . : : , . . . , ., . ., ; ,: , : .:. .. .: . , . . . . : . : . : . .
2~QQ~6S
Rl R2 B V RB Rg 4-CF3 H C2Me S Me O-n-dodecyl 4-CF35-Br H O Me 0-6ec-Bu 4-C15-Br H O Me O-~ec-Bu 4-Br 5-Br H O Me O-sec-Bu 4-OCF35-Br H O Me O-sec-~u 4-CF35-Cl H O Me 0-6ec-~u 4-C15-Cl H O Me O-~ec-Bu 4-Br 5-Cl H O Me O-cec-Bu 4-CF35-CF3 H o Me O-~ec-Bu 4-CF34-F H O Me O-~ec-Bu 4-CF3 H H O Me 0-6ec-Bu 4-CF35-Br C02Me O Me 0-6ec-Bu 4-CF35-Cl C02Me O Me O-sec-Bu 4-CF35-CF3 C02Me O Me O-~ec-Bu 4-CF34-F C02Me O Me O-~ec-Bu 4-CF3 H C02Me Me O-sec-Bu 4-CF35-Cl H S Me O-~ec-Bu 4-C15-Cl H S Me 0-6ec-Bu ::
4-Br 5-Cl H S Me O-sec-Bu 4-CF35-Br H S Me O-sec-Bu 4-CF35-F X S Me 0-6ec-Bu 4-CF34-Cl H S Me O-sec-Bu 4-CF34-F H S Me O-sec-Bu 4-CF3 H H S Me 0-6ec-Bu 4-CF35-Cl C02Me S Me O-sec-Bu 4-CF35-Br C02Me S ~e O-cec-Bu 4-CF35-F C~2Me S Me O-sec-Bu 4-CF34-Cl C02Me S Me O-sec-Bu 4-CF34-F C02Me S Me O-cec-Bu 4-CF3 H C02Me S Me O-sec-Bu .: ., , , . . . . . . : . : : ,: : : :.
~ . ~ . . . .
2~Q~65 . Rl R2 B V R~ R9 S
4-CF35-Br H O Me O-iPr 4-C15-Br H O Me O-iPr 4-8r 5-Br ~ O Me O-iPr 4-OCF35-Br H O Me O-iPr 4-CF35-Cl H O Me O-iPr 4-C15-Cl H O Me O-iPr 4-8r 5-Cl H O Me O-iPr 4-CF35-CF3 H O Me O-iPr 4-CF34-F H O Me O-iPr 4-CF3 H H O Me O-iPr 4-CF35-Br CO2Me O Me O-iPr 4-CF35-Cl CO2Me O Me O-iPr 4-CF35-CF3 CO2Me O Me O-iPr 4-CF34-F CO2Me O Me O-iPr 4-CF3 ~ CO2Me O Me O-iPr 4-CF35-Cl H S Me O-iPr 4-C15-Cl H S Me O-iPr 4-Br 5-Cl H S Me O-iPr 4-CF35-Br H S Me O-iPr 4-CF35-F H S Me O-iPr 4-CF34-Cl H S Me O-iPr 4-CF34-F H S Me O-iPr q-CF3 H H S Me O-iPr 4-CF35-Cl CO2Me S Me O-~Pr 4-CF35-Br CO2Me S Me O-iPr 4-CF35-F CO2Me S Me O-iPr 4-CF34-Cl CO2Me S Me 9-iPr 4-CF34-F CO2Me S Me O-iPr 4-CF3 ~ CO2Me S Me O-iPr . . . , : , .. : ... , ~, : - .. . .
2~?~Q~65 1 R2 B V R8 Rg 4-CF35-Br H , O Me OCH2CH2Et 4-C15-~r H O Me OCH2CH2OEt 4-Br S-Br ~ O Me OCH2CH2OEt 4-OCF35-Br H O Me OCH2CH2OEt 4-CF35-Cl H O Me OCH2CH2OEt 4-C15-Cl H O Me OCH2CH2OEt 4-Br 5-Cl H O Me OCH2CH2OEt 4-CF3 s-CF3 H o Me OCH2CHzOEt g-CF34-F H O Me OCH2CH2OEt 4-CF3 H H O Me OCH2CB2OEt 4-CF35-Br CO2Me O Me OCH2CH2OEt 4-CF35-Cl CO2Me O Me OCH2CH2OEt 4-CF35-CF3 CO2Me O Me OCH2CH2OEt 4-CF34-F CO2Me Me OCH2CH2OEt 9-CF3 H CO2Me Me OCH2CH2Et 4-CF35-Cl H S Me OCH2CH2OEt 4-C15-Cl H S Me OCH2CH2OEt 4-Br 5-Cl H S Me OCH2CH2OEt 4-CF35-Br H S Me OCH2CH2OEt 4-CF35-F H S Me OCH2CH2OEt 4-CF34-Cl H S Me OCH2CH2OSt 4-CF34-F H S Me OCH2CH2OEt 4-CF3 H H S Me OCH2CH2OEt 4-CF35-Cl CO2Me S Me OCH2CH2OEt 4-CF35-Br CO2Me S Me OCH2CH2OEt 4-CF35-F CO2Me S Me OCH2CH2OEt 4-CF34-Cl CO2Me S Me OCH2CH2OEt 4-CF34-F CO2Me S Me OCH2CH2OEt 4-CF3 H CO2Me S Me OCH2CH2OEt ''''''"' .
- . . . . . : , . . . :.
Z~C~Q~6~;
1 R2 B V Rg Rg 4-CF35 Br H O Me OCH2CC13 4-C15-Br H O Me OCH2CC13 4-Br 5-Br H O Me OCH2CC13 4-OCF35-8r H O Me OCH2CC13 4-CF35-Cl H O Me OCH2CC13 4-C15-Cl H O Me OCH2CC13 4-Br 5-Cl H O Me OCH2CC13 4-CF3 s-CF3 H o Me OCH2CC13 4-CF34-F H O Me OCH2CC13 4-CF3 H H O Me oCH2CC13 4-CF35-Br CO2Me O Me OCH2CC13 4-CF35-Cl CO2Me O Me OCH2CC13 4-CF35-CF3 CO2Me o Me OCH2CC13 4 CF34 F CO2Me O Me OCH2CC13 4-CF3 H CO2Me Me OCH2CC13 4-CF35-CI H S Me OCH2CC13 4-C15-Cl H S Me OCH2CC13 4-Br 5-Cl H S Me OCH2CC13 4-CF35-Br H S Me OCH2CC13 4-CF35-F H S Me OCH2CC13 4-CF34-Cl H S Me OCH2CC13 4-CF34-F H S Me OCH2CC13 4-CF3 H H S Me OCH2CC13 4-CF35-Cl C~2Me S Me OCH2CC13 4-CF35-i3r CO2Me S Me OCH2CC13 4-CF35-F CO2Me S Me OCH2CC13 4-CF34-Cl CO2Me S Me OCH2CC13 ~-CF34-F CO2Me S Me OCH2CC13 4-CF3 H CO2Me S Me OCH2CC13 2~Q~6~;
Rl R2 ~ V R8 Rg _ 4-CF35-Br B O Me OCH2CF3 4-Cl S-Br H O Me OCHzCF3 4-Br 5-Br N O Me GCH2CF3 4-OCF35-Br H O Me OCH2CF3 4-CF35-Cl H O Me OCH2CF3 4-C15-Cl H O Me OCH2CF3 4-Br 5-Cl H o Me OCH2CF3 4-CF35-CF3 H O Me OCH2CF3 4-CF34-F H O Me OCH2CF3 4-CF3 H H O Me OCH2CF3 4-CF35-Br CO2Me O Me OCH2CF3 4-CF35-Cl CO2Me O Me OCH2CF3 4-CF35-CF3 CO2Me O Me OCH2CF3 4-CF34-F CO2Me Me OCH2CF3 4-CF3 H CO2Me Me OCH2CF3 4-CF35-Cl H S Me OCH2CF3 4-C15-Cl H S Me OCH2CF3 4-Br 5-Cl H S Me OCH2CF3 4-CF35-Br H S Me OCH2CF3 4-CF35-F H S Me OCH2CF3 4-CF34-Cl H S Me OCH2CF3 4-CF34-F H S Me OCH2CF3 4-CF3 H H S Me OCH2CF3 4-CF35-Cl CO2Me S Me OCH2CF3 4-CF35-Br CO2Me S Me OCH2CF3 4-CF35-F CO2Me S Me OCH2CF3 4-CF34-Cl CO2Me S Me OCH2CF3 4-CF34-F C02Me S Me OCH2CF3 4-CF3 H C02Me S Me OCH2CF3 . , .......... . , , . . ~ . ...... . . . . . .
.. . ~ . . , , . . , , .. - , .... . .
- . . ~ . . . .
2~?QQ~6~
Rl R2 ~ V R8 R9 4-CF35-9r H O Me CH2c2Et 4-C15-Br H O Me OCH2CO2Et 4-8r 5-Br H o Me CH2c2Et 4-OCF35-8r H O Me OCH2CO2Et 4-CF35-Cl H O Me OCH2C02Et 4-Cl S-Cl H O Me OCH2C02Et 4-Br 5-Cl H O Me OCHzCO2Et q-CF35-CF3 H o Me OCH2C02Et 4 CF34 F H O Me CH2c2Et 4-CF3 H H O Mç OCH2CO2Et 4-CF35-~r CO2Me O Me OCH2C02Et 4-CF35-Cl CO2Me O Me OCH2C02Et 4-CF35-CF3 CO2Me O Me OCH~C02Et 4-CF34-F CO2Me O Me OCH2C02Et 4-CF3 H CO2Me Me CH2c2Et 4-CF35-Cl H S Me OCH2CO2Et 4-CI 5-Cl H S Me OCH2C02Et 4-Br 5-Cl H S Me OCH2CO2Et 4-CF35-8r H S Me OCB2C02Et 4-CF35-F H S Me OCH2CO2Et 4-CF34-Cl H S Me OCH2C02Et 4-CF34-F H S Me OCH2C02Et 4-CF3 H H S Me OCH2C02Et 4-CF35-Cl CO2Me S Me OCB2C02Et 4-CF35-8r CO2Me S Me OCH2C02Et 4-CF35-F CO2Me S Me OCH2C02Et 4-CF34-Cl CO2Me S Me OCB2C02Et 4-CF34-F CO2Me S Me OCN2C02Et 4-CF3 H CO2Me S Me OCH2C02St '~ .' ' .... .... .. . . .... . . .
2C~Q~6~
1 R2 ~3 V R8 Rg 4-CF3 5-Br H O Me F
4-C1 5-Br H O Me F
4-Br S-i3r H O Me F
4-OCF35-Br H O Me F
4-CF3 5-Cl R O Me F
4-C1 5-Cl H 1~ Me F
4-Br 5-Cl H O Me F
4-CF3 5-CF3 H O Me F
4-CF3 4-F H O Me F
lS 4-CF3 H H Me F
4-CF3 5-Br CO2Me O Me F
4-CF3 5-Cl C02Me O Me F
4-CF3 S-CF3 C02Me O Me F
4-CF34-F CO2Me Me F
4-CF3 H CO2Me Me F
4-CF3 5-Cl H S Me F
4-C1 5-Cl H S Me F
4-Br 5-Cl H S Me F
4-CF3 5-Br H S Me F
4-CF3 5-F H S Me F
4-CF3 4-Cl H S Me F
4-CF3 4-F H S Me F
4-CF3 H H S Me F
4-CF35-Cl CO2Me S Me F
3Q 4-CF3 5-Br CO2Me S Me F
4-CF35-F CO2Me S Me F
4-CF34-Cl CO2Me S Me F
4-CF34-F C2Me S Me F
4-CF3 H CO2Me S Me F
~., , - : . - : . -, .. -- - : , :: : :.. :: . , . : ~ . . . : . -Z~ 6~;
96 ~.
Rl R2 B V R8 Rg ,.,~, ~.
4-CF3 5-8r X O Me NMe2 4-Cl S-Br H O Me NMe2 ..
4-Br 5-8r N O Me NMe2 4-OCF35-Br H O Me NMez 4-CF3 5-Cl H O Me NMe2 4-C1 5-Cl H O Me NMe2 4-Br 5-Cl H O Me NMe2 4-cF3 5-cF3 H O Me NMe2 4-CF3 4 F H O Me NMe2 4-CF3 H H O Me NMez 4-CF3 5-Br C02Me O Me NMe2 4-CF3 5-Cl CO2Me O Me ~Me2 :
4-cF3 5-cF3 co2Me O Me NMe2 .:
4-CF34-F CO2Me Me NMe2 4-CF3 H CO2Me Me NMe2 4-CF3 5-Cl H S Me NMe2 4-C1 5-Cl H S Me NMe2 4-Br 5-Cl H S Me NMe2 4-CF3 5-Br H S Me NMe2 ':
4-CF3 5 F H S Me NMe2 4-CF3 4-Cl H S Me NMe2 4-CF3 4 F H S Me NMe2 4-CF3 H H S Me NMe2 4-CF35-Cl t:O2Me S Me NMe2 4_CF35-Br CO2Me S Me NMe2 4-CF35-F CO2Me S Me NMe2 : .
4-CP34-Cl CO2Me S Me NMe2 4-CF34-F C2Me S Me ~Me2 4-CF3 H C2Me S Me NMe2 :
, .. . - . :-:: - ., : .: ; . . ..
.,. ! ~ . . . .
', .~. '''' ' '.', ' ., ' "' ' . ' . ' , ' . ', '''' .. .. ' , ' .
2~t~Qt~iS
Rl R2 B V Pg Rg 4-CF35-Br H O Et O-iPr 4-C15-~r ~ O Et O-iPr 4-~3r S-Br ~ O Et O-iPr 4-OCF35-Br H O Et O-iPr 4-CF35-Cl H O Et O-iPr 4-C15-Cl H O Et O-iPr 4-Br 5-Cl H O Et O-iPr 4-CF35-CF3 H o Et O-iPr 4-CF34-F H O Et O-iPr 4-CF3 H H O Et O iPr 4-CF35-Br CO2Me O Et O-iPr 4-CF35-Cl CO2Me O Et O-iPr 4-CF35-CF3 CO2Me O Et O-iPr 4 CF34 F CO2Me Et O-iPr 4-CF3 H CO2Me O Et O-iPr 4-CF35-Cl H S Et O-iPr 4-C15-Cl H S Et O-iPr 4-Br 5-Cl H S Et O-iPr 4-CF35-Br H S Et O-iPr 4-CF3 S-F H S Et O-iPr 4-CF34-Cl H S Et O-iPr 4-CF34-F H S Et O-iPr 4-CF3 H H S Et O-iPr 4-CF35-Cl CO2Me S Et O-iPr 4-CF35-Br CO2Me S Et O-iPr 4-CF35-F C02Me S Et O-iPr 4-CF34-Cl CO2Me S Et O-iPr 4-CF34-F CO2Me S Et O-iPr 4-CF3 H CO2Me S Et O-iPr .' ' ., . ' : ', " ~ ' , ' ' ' .: ' ' ' , ' ' ' ' Z~Q~65 Rl R2 B V R8 Rg 4-CF35-Br H O iPr OEt 4-C15-Br H O iPr OEt 4-Br 5-Br H O iPr OEt 4-OCF35-Br H O iPr OEt 4-CF35-Cl H O iPr OEt 4-C15-Cl H O iPr OEt 4-Br 5-CI H O iPr OEt 9-CF35-CF3 H O iPr OEt 4-CF34-F H O iPr OEt 4-CF3 H H O iPr OEt 4-CF35-Br CO2Me O iPr OEt 4-CF35-Cl CO2Me O iPr OEt 4-CF35-CF3 CO2Me O iPr OEt 4-CF34-F CO2Me O iPr OSt 4-CF3 H CO2Me iPr OEt 4-CF35-Cl H S iPr OEt 4-C15-Cl H S iPr OEt 4-Br 5-Cl H S iPr OEt 4-CF35-Br H S iPr OEt 4-CF35-F H S iPr OEt 4-CF34-CI H S iPr OEt 4-CF34-F H S iPr OEt 4-CF3 H H S iPr OEt 4-CF35-C~ C~2Me S iPr OEt 4-CF35-Br CO2Me S iPr OEt 4-CF35-F CO2Me S iPr OEt 4-CF34-C~ CO2Me S iPr OEt 4-CF34-F C2Me S iPr OEt 4-CF3 H CO2Me S iPr OEt - : . . . :
- . , ~3Q~6S
4-CF35-9r H O iPr O-nBu 4-C15-Br H O iPr O-nBu 4-Br 5-Br H O .iPr O-nBu 4-OCF35-Br H O iPr O-nBu 4-CF35-Cl H O iPr O-nBu 4-C15-Cl H O iPr O-DBu ' 4-Br 5-Cl H O iPr O-nBu 4-CF35-CF3 H o iPr O-nBu 4-CF34-F H O iPr O-~Bu lS 4-CF3 H H iPr O-nBu 4-CF35-Br C02Me O iPr O-nBu 4-CF35-Cl C02Me O iPr O-nBu 4-CF35-CF3 C02Me O iPr O-nBu 4-CF34-F C02Me O iPr O-nBu 4-CF3 H C02Me iPr O-nBu 4-CF35-Cl H S iPr O-nBu 4-C15-Cl H S iPr O-nBu 4-Br 5-Cl H S iPr O-nBu 4-CF35-Br H S iPr O-nBu 4-CF35-F H S iPr O-nBu ;
4-CF34-C18 S iPr O-nBu 4-CF34-F H S iPr O-nBu 4-CF3 H H S iPr O-nBu 4-CF35-Cl C02Me S iPr O-nBu 4-CF35-Br C02Me S iPr O-nBu 4-CF35-F C02Me S iPr O-nBu 4-CF34-Cl C02Me S iPr O-nBu 4-CF34-F C02Me S iPr O-nBu 4-CF3 H C02Me S iPr O-DBu , '~
. . .. , -:: .: : ~ . , :. , , : :
.. ., : .. : .. - . . . : " . ~::
2~ Q~6S
100 :, Rl R2 B V R8 Rg , 4-CF3 5-Br H O iPr OCH2cF3 4-C1 5-Br H O iPr OCH2CO2Me 4-Br 5-Br H O iPr NMe2 4-OCF3 5-Br H O iPr NEt2 4-CF3 5-Cl H O iPr piperidino 4-C1 5-Cl H O iPr Et 4-Br 5-Cl H O iPr 4-Br-Ph 4-CF3 5-CF3 H O CH2Ph OEt 4-CF3 4-F H O CH2Ph O-n-octyl 4-CF3 H H O CH2Ph OCH2CO2Et 4-CF3 5-Br CO2Me CH2Ph F
4-CF3 5-Cl CO2Me CH2Ph NEt2 4-CF3 5-CF3 CO2Me O CH2Ph morpholino .;
4-CF3 4-F CO2Me CH2Ph 4-Cl-Ph 4-CF3 H CO2Me O CH2Ph Et . .
4-CF3 5-Cl H S CH2Ph Ph . . . - .. - . . : ,: . . , , . :
- . : . .: . . - :
- . : . - . .. :
. , - - - . ; . - :. . - : : : -. . . : , , : , . . .
-2~ 65 ~ble 9 Rl .:
~ N O
O S-N-S-R~
R~O
Rl R2 B V R8 Rg 4-CF3 5-Br H O Me NMe2 4-C1 5-Br H O Me NMe2 -4-Br 5-Br H O Me NMe2 4-OCF3 5-Br H O Me NMe2 4-CF3 5-Cl H O Me NMe2 4-C1 5-Cl H O Me NMe2 3~ 4-Br 5-Cl H O Me NMe2 :-4-CF3 s-CF3 H o Me NMe2 4-CF3 4 F H O Me NMe2 :
4-CF3 H H O Me NMe2 q-CF3 s-Br CO2Me O Me NMe2 ~:
4-CF3 5-Cl CO2~e O Me NMe2 .
',:
!~
..
.' , , .
'; ' ; ' ' ~ . ' ' ' ' ' i ~ . . ! .
2~ 6s Rl R2 B V R8 Rg 4-CF35-CF3 CO2Me O Me NMe2 4-CF34-F C02Me Me NMe2 4-CF3 H CO2Me O Me NMe2 4-CF35-Cl H S Me NMe2 9-C15-Cl H S Me NMe2 4-Br 5-Cl H S Me NMe2 4-CF35-Br H S Me NMe2 4 CF35 F H S Me NMe2 4-CF34-Cl H S Me NMe2 4-CF34-F H S Me NMe2 4-CF3 H H S Me NMe2 4-CF35-Cl CO2Me S Me NMe2 4-CF35-Br CO2Me S Me NMe2 4-CF35-F CO2Me S Me NMe2 4-C}34-Cl CO2Me S Me NMe2 4-CF34-F CO2Me S Me NMe2 4-CF3 H CO2Me S Me NMe2 4-CF35-Br H O Me NEt2 4-C15-Br H O Me NEt2 4-Br 5-Br H O Me NEt2 4-OCF35-Br ~ O Me NEt2 4-CF35-Cl H O Me NEt2 4-C15-Cl H O Me NEt2 4-Br 5-Cl H O Me NEt2 4-CF35-CF3 H O Me NEt2 4-CF34-~ H O Me NEt2 4-CF3 H H O Me NEt2 4-CF35-Br CO2Me O Me NEt2 4-CF35-Cl CO2Me O Me NEt2 4-CF35-CF3 CO2Me O Me NEt2 4-CF34-F CO2Me O Me NEt2 4-CF3 H CO2Me Me NEt2 , ;'.' ` ''~ ' , ~', " " ' . ', ', . . ' ' .
, ", 2~7~Q~6S
R2 B V R8 Rg 4-CF35-Cl H S Me NEt2 4-C15-Cl H S Me NEt2 4-Br 5-Cl H S Me NEt2 4-CF35-~r H S Me NEt2 10. 4-CF35-F H S Me NEt2 4-CF34-C18 S Me NEt2 4-CF34-F H S Me NEt2 4-CF3 H ~ S Me NEt2 4-CF35-Cl CO2Me S Me NEt2 lS 4-CF35-Br CO2Me S Me NEt2 4-CF35-F CO2Me S Me NEt2 4-CF34-Cl CO2Me S Me NEt2 4-CF34-F CO2Me S Me NEt2 4-CF3 H CO2Me S Me NEt2 4-CF35-Br H O Me piperidino 9-C15-Br H O Me 6ec-Bu 4-Br 5-9r H O Me D-he~yl 4-OCF35-Br H O Me Ph .
4-CF35-Cl H O Me 4-Cl-Ph :
4-C15-Cl H O Me 4-Me-Ph :
4-Br 5-Cl H O Me n-Bu 4-CF35-CF3 H O Et NMe2 4-CF34-F H O Et NEt2 4-CF3 H H O Et morpboli~o :
4 CF35-S3r CO2Me O Et ~Pr 4-CF35-Cl CO2Me O Et n-Bu 4-CF35-CF3 CO2Me O Et Ph 4-CF34-F CO2~e O Et 4-M~O-Ph !;``
q-CF3 H CO2Me Me NMe2 4-CF35-Cl H S Me NEt2 4-C15-Cl H S Me morpholiDo 4-9r 5-Cl H S Me iPr ,, .. : . : ., . , ... . ~:. : .. .. .
Rl R2 B V R8 R9 -.4-CF35-Br H S Me n-B~.
4-CF35-F H S Me Ph 4-CF34-Cl X. S Me 4-MeO-Ph 4-CF34-F B S Et piperidioo 4-CF3 H H S Et 6ec-Bu 4-CF35-Cl CO2Me S Et n-hesyl 4-CF35-Br C02Me S Et Ph 4-CF35-F CO2Me S Et 4-Cl-Ph 4-CF34-Cl CO2Me S Et 4-Me-Ph 4-CF34-F COzMe S Et n-Bu 4-CF3 H CO2Me S Et 2,6-~i-Me-morpholino 4-CF35-Br H O iPr NMç2 4-Cl S-Br H O iPr NMe2 4-8r 5-Br H O iPr NMe2 4-OCF35-Br H O iPr NMe2 4-CF35-Cl H O iPr ~Me2 4-Cl S-Cl H O iPr NMe2 4-Br 5-Cl H O iPr NMe2 4-CF35-CF3 H O iPr NMe2 4-CF34-F H O iPr NMe2 4-CF3 H H O lPr NMe2 :~
4-CF35-Br CO2Me O iPr 'NMe2 4-CF35-Cl CO2Me O iPr NMe2 4-CF35-CF3 CO2Me O iPr NMe2 4-CF34-F C02Me iPr NMe2 4-CF3 H C02Me lPr NMe2 , 4-CF35-Cl H S iPr NMe2 :
4-C15-Cl H S iPr NMe2 4-Br 5-Cl H S iPr N~.e2 4-CF35-Br H S iPr NMe2 4-CF35-F H S iPr NMe2 :.
, -, :
2C~Q~L65 105 ..
Rl R2 B V R8 Rg __ S .
4-CF3 4-Cl H S iPr NMe2 4-CF3 4-~ H S iPr NMe2 4-CF3 H H S iPr NMe2 4-CF3 5-Cl C02Me S iPr NMe2 4-CF3 5-Br CO2Me S iPr NMe2 4-CF3 S-F CO2Me S iPr NMe2 4-CF3 4-Cl C02Me S iPr NMe2 4-CF3 4-F CO2Me S iPr NMe2 4-CF3 H CO2Me S iPr NMe2 :
21~ 65 Table 10 lC
~ N Y
O S-N-P-Y Rlo R~Y Rll Rl R2 B V R8 Y . Y Rlo Y Rll 4-CF3 5-Br H O tBu S OEt OEt 4-.C1 5-Br H O tBu S OEt OEt 4-Br 5-Br H O tBu S OEt OEt 4-OCF3 5-Br H O tBu S OEt OEt 4-CF3 5-Cl H O tBu S OEt OEt 4-C1 5-Cl H O tBu S OEt OEt 4-Br 5-Cl H O tBu S OEt OEt 4-CF3 5-CF3 H O tBu S OEt OEt 4-CF3 4-F H O tBu S OEt OEt 4-CF3 H H O tBu S OEt OEt 4-CF3 5-Fr CO2Me O tBu S OEt OEt 4-CF3 5-Cl CO2Me O tBu S OEt OEt 4-CF3 S-CF3 C02Me O tBu S OEt OEt 3~
- ~ ~ : , ::, . -, . :
- - . : . . ... .
Q~65 Rl R2 B V R8 Y y Rlo Y R
.
4 CF34 F CO2Me O tBu S OSt OEt 4-CF3 H CO2Me O tBu S OEt OEt 4-CF35-Cl H S t8u S OEt OEt 4-C15-Cl H S t8u S OEt OEt 4-Br 5-Cl H S tBu S OEt OEt 4-CF35-Br H S tBu S OEt OEt 4-CF35-~ R S tBu S OEt OEt 4-CF34-Cl H S tBu S OEt OEt 4-CF34-F H S tBu S O~t OEt 4-CF3 H H S tBu S OEt OEt 4-CF35-Cl CO2Me S tBu S OEt OEt 4-CF35-Br CO2Me S tBu S OEt OEt 4-CF35-F CO2Me S tBu S OEt OEt 4-CF34-Cl CO2Me S tBu S OEt OEt 4-C~34-~ CO2Me S tBu S OEt OEt 4-CF3 H CO2Me S tBu S OEt OEt 4-CF35-Br N O tBu S -OCH2C(Me)2CH2O-4-C15-Br H O tBu S -OCH2C(Me)2CH2O-4-Br 5-Br H O tBu S -OCH2C(Me)2CB2O-4-OCF35-Br H O tBu S -OCH2C(Me)2CH2O-4-CF35-CI H O tBu S -OCH2C(Me)2CH2O_ 4-C15-Cl H O tBu S -OCH2C(Me)2CH2O-4-Br S-Cl H O tBu S -OCH2C(Me)2CH2O-4-CF35-CF3 H O tBu S -OCH2C(Me)2CH2O-~n 4-CF34-F H O tBu S -OCH2C(Me)2CH2O-4-CF3 H H O tBu S -OCH2C(Me)2CB2O-4-CF35-i3r CO2Me O tBu S -OCH2C(Me)2CH2O-4 CF35-Cl CO2Me O tBu S -OCH2C(Me~2CH2O-4-CF35-CF3 CO2Me O tBu S -OCH2C(Me)2CN2O-4-CF34-F CO2Me O tBu S -OCH2C(Me)2CH2O-4-CF3 H CO2Me O tBu S -OCH2C(Me)2CH2O-4-CF3 5-Cl H S tBu 5 -OCH2C(Me)2CH2O-'`'"
. . .
':~., - . . . . . . . . .: .. . ~ :. .; .: :,. .: .. .
2~ 65 Rl R2 El V R8 Y ' Y Rlo Y Rll 4-C15-Cl H S tBu S -OCH2C(Me)2CH2O_ q-Br 5-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF35-Br H S tBu S -OCHzC(Me)2CH2O-4-CF35-F N S tBu S OCH2C(Me)2CH2O-4-CF34-Cl H S tBu S -OCH2C(Me)2CH2O-4-CF34-F H S tBu S -OCH2C(Me)2CB2O- ~.
4-CF3 H H S tBu S -OCH2C(Me)2CH2O-4-CF3 ~-Cl CO~e S tBu S -OCH2C(Me)2CH20-4-CF35-~ CO2Me S tBu S -OC~2C~Me)2CH2O_ 4-CF35-F C02Me S tBu S -OCH2C(Me)2CH2o-4-CF34-Cl C02Me S tBu S -OCH2C(Me)2CH2O-4-CF34-~ CO2Me S tBu S -OCH2C(~e)2CH2O-4-CF3 H C02Me S tBu S -OCH2C(Me)2CH2O-4-CF35-Br H O tBu S OCH2CH2CH20-4-Cl S-Br H O tBu S -OCH2CH2CH20- .
4-Br 5-Br H O tBu S -OCH2CH2CH20-4-OCF35-Br H O tBu S -CH2cH2cH2- l~
4-CF35-Cl H O tBu S -OCH2CH2CH20- ~. -4-Cl S-Cl H O tBu S -CH2cH2cH2-4-Br 5-Cl H O tBu S -OCH2CH2CH2O-4-CF35-CF3 H o tBu S -OCH2CH2CH2O-4-CF34-F H O tBu S -OCH2CH2CH2O-4-CF3 H H O tBu S -OCH2CH2CH2O- ~:
4-CF35-Br CO2Me O tBu S -OCH2CH2CH2O-4-CF35-Cl C02Me O tBu S -OCH2CH2CH20- : :
4-CF35-CF3 CO2Me O tBu S -CH2cH2cH2-4-CF3 ~-F CO2Me O tBu S -OCH2CH2CH2O-q-CF3 H C02Me tBu S -CH2cH2cH2-4-CF35-Cl H S tBu S OCH2CH2CH20-4-C15-Cl H S tBu S -OCH2CH2CH2O-4-Br 5-Cl H S tBu S -C~2cH2cH2- ;
,, . ~ . , . . , . .... ~ .. ., . , , . . . .. - : . ..
Rl R2 B V R8 Y Y al0 Y Rll 4-CF35-Br H . S tBu S -OCH2CH2CH2O
4-CF35-F H S tBu S -OCH2CH2CH2O-4-CF34-Cl U S tBu S -OCH2CH2C-H20 4-CF34-F N S tBu S -CH2cH2cH2- !`
4-CF3 H H S tBu S -OCH2CH2CH2O-4-CF3 5-Cl CO2Me S tBu S -QCH2CH2CH2O-4-CF3 5-Br CO2Me S t8u S -OCH2CH2CH2O-4-CF3 5-F CO2Me S tBu S -OCH2CH2CH2O-4-CF3 4-Cl CO2Me S tBu S -OCH2CH2cH2O- :
4-CF34-F CO2Me S tBu S -OCH2CH2CH2O-4-CF3 H CO2Me S tBu S -OCH2CH2CH2O-4-CF35-8r H O t8u S OCHzCH2O
4-C15-8r H O tBu S -OCH2C~2O-4-Br 5-Br H O tBu S -OCH2CH2O-2C 4-OCF35-Br H O tBu S -OCH2CH2O-4-CF35-Cl H O tBu S -OCH2CH2O-4-C15-Cl H O tBu S -OCH2~2O-4-Br S-Cl H O tBu S -OCH2CH2O-4-CF35-CF3 H O tBu S -OCH2CH2O-4-CF34-F H O tBu S -OCH2CH2O-4-CF3 H H O tBu S -OCHzCH2O-4-CF35-Br CO2Me O tBu S -OCH2CH2O- .. -4-CF35-Cl CO2Me O tBu S -OCH2CH2O-4-CF35-CF3 CO2Me O tBu S -CH2cH2 . ~`
4-CF34-F CO2Me tBu S -OCH2CH2O-4-CF3 H CO2Me O tBu S -OCH2CH2O- ~
4-CF35-Cl H S tBu S -OCH2CH2O- , -4-Cl S-Cl H S tBu S -CH2cH2- `~ :
4-Br S-Cl H S tFu S -OCH2CH2O-4~CF35-Br H S tBu S -CH2~2-4-CF35-~ H S t8u S -OCH2CH2O- ..
4-CF34-Cl H S tBu S -OCH2CH2O-., :, -. , . .. , , . - . : :. . ~ . ..... : . : - : :::, ,: .
:. . , ,, ,. , ,: .. ,..~, . ;'. '-, '.. ' , . -: : '' ' :': ' '. " ' ;' ., ' ': ~ '. -'." .-'', :. ' . , .'',.,... ,. ':, ,, ' ~Q~6S
R2 B V RB ~ ~ Rlo Y Rll 4 CF34 F ~ S t~u S -OCH2CH20-4-CF3 H B S tBu S OC~2CH20-4-CF35-Cl CO2Me S tBu S -OCH2CH~O-4-CF35-~r CO2Me S tBu S -OCH2CH20-4-CF35-F CO2Me S tBu S -OCH2CB20-4-CF34-CI COzMe S tBu S -OCH2CH20-q-CF34-F CO2Me S tBu S -OCH2CH20-4-CF3 H CO2Me S tBu S -OCH2C~20-4-CF35-Br H O iPr S OEt OEt 4-C15-8r H O iPr S OEt OEt 4-Br S-Br H O $Pr S OEt OEt 4-OCF35-Br H O iPr S OEt OEt 4-CF35-Cl H O iPr S OEt OEt 4-C15-Cl H O iPr S OEt OEt 4-Br 5-Cl H O iPr S OEt OEt 4-CF35-CF3 H o iPr S OEt OEt 4-CF34-F H O iPr S OEt OEt 4-CF3 H B O iPr S OEt OEt 4-CF35-8r CO2Me O iPr S OEt OEt 4-CF35-Cl CO2Me O iPr S OEt OEt 4-CF35-CF3 CO2Me O iPr S OEt OEt 4-CF34-F CO2Me iPr S OEt OEt 4-CF3 H CO2Me iPr S OEt OEt .
4-CF35-Cl H. S iPr S OEt OEt 4-C15-Cl H S iPr S OEt OEt 4-Br S-Cl H S iPr S OEt OEt 4-CF35-~r H S iP~ S OEt OEt 4-CF35-F H S iPr S OEt OEt 4-CF34-Cl H S iPr S OEt OEt 4-CF34-F H S iPr S OEt OEt 4-CF3 H H S iPr S OEt OEt 4-CF35-Cl CO2Me S iPr S OEt OEt : -: . : . . .: ~ .: . : . .
.. .... . . . . .. . . ... : .:
2~ 6~;
Rl R2 B V R8 Y y Rlo Y Rll 4-CF35-Br CO2Me S iPr S OEt OEt 4 CF35 F CO2Me S iPr S OEt OEt 4-CF34-Cl CO2Me S iPr S OEt OEt 4-CF34-F CO2Me S iPr S OEt OEt 4-CF3 N CO2Me S iPr S OEt OEt 4-CF35-Pr H O iPr S -OCH2C(Me)zCH2O-4-C15-Br H O iPr S -OCH2C(Me)2CH2O-9-Br S-Br ~ O iPr S -OCH2C(Me)2CH2O-4-OCF35-Br H O iPr S -OCH2C(Me)2CH20-4-CF35-Cl H O iPr S -OCH2C(Me)2CH2O-4-C15-Cl H O iPr S -OCH2C(Me)2CH2O-4-Br 5-Cl H O iPr S -OCH2C(Me)2CH2O-4-CF35-CF3 H o iPr S -OCB2C(Me)2CH2O_ 4-CF34-F H O iPr S -OCH2C(Me)2CH2O-4-CF3 H H O iPr S-OCH2C(Me)2CH2O-4-CF35-Br CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF35-Cl CO2Me O iPr S OCH2C(Me)2cH2O-4-CF35-CF3 CO2Me OiPr S -OCH2C(Me)2CH2O-4-CF34-F CO2Me O iPr S -OCH2C(Me)2CH2O-4-CF3 H CO2Me iPr S -OCH2C(Me)2CH2O-4-CF35-Cl H S iPr S -OCH2C(Me)2CH2O-4-C15-Cl H - S iPr S -OCH2C(Me)2CH2O-4-Br 5-Cl H S iPr S -OCH2C(Me)2CB2O-4-CF35-Br H S iPr S -OCH2C(Me)2CH2O-4-CF35-F H S iPr S -OCH2C(Me)2CH2O-4-CF34-Cl H S iPr S -OCH2C(Me)2CH2O-4-CF34-F H S iPr S -OCH2C(Me)2CH2O-4-CF3 H H S iPr S -OCH2C(Me)2CH2O-4-CF3 5-Cl CO2Me SiPr S -OCH2C(Me)2CH2O-4-CF3 5-Br CO2Me SiPr S OCH2C(Me)2c~2O-4-CF3 5-F CO2Me SiPr S -OCH2C(Me)2CH2O-~,:
~ .
'' ' ' ':
. . ~ . : :, : , .... ,, , . ,. :: . . ,, . .. . . ::
.: ,, , ~ : . , , .:
r~ , ~o~s ~1 R2 B V R8 Y Y ~1~ Y Rll ;
4-CF34-Cl CO2Me S iPr S -OCH2C(Me)2CH20-4 CF34 F CO2Me S iPr S -OCH2C(Me)2CH20-4-CF3 H CO2Me S iPr S _ocH2c(Me)2~H2 4-CF35-~r ~ O Me S OEt OEt 4-C15-8r H O Me S OEt OEt 4-Br 5-Br H O Me S OEt OEt 4-OCF35-Br H O Me S OEt OEt 4-CF35-Cl H O Me S OEt OEt 4-C15-Cl R O Me S OEt OEt 4-iBr 5-Cl H O Me S OEt OEt 4-CF35-CF3 H O Me S OEt OEt 4-CF34-F H O Me S O~t OEt 4-CF3 H H O Me S OEt OEt 4-CF35-Br C02Me O Me S OEt OEt 4-CF35-Cl CO2Me O Me S OEt OEt 4-CF35-CF3 CO2Me O Me S OEt OEt 4-CF34-F C02Me O Me S OEt OEt 4-CF3 H CO2Me Me S OEt OEt 4-CF35-Cl H S Me S OEt OEt 4-C15-Cl H S Me S OEt OEt 4-Br 5-Cl H S Me S OEt OEt 4-CF35-Br H S Me S OEt OEt 4-CF35-F H S Me S OEt OEt 4-CF34-Cl H S Me S OEt OEt 4-CF34-F H S Me S OEt OEt 4-CF3 H H S Me S OEt OEt 4-CF35-Cl CO2Me S Me S OEt OEt 4-CF35-Br CO2Me S Me S OEt OEt .:
4-CF35-F CO2Me S Me S OEt OEt 4-CF34-Cl C02Me S Me S OEt OEt 4-CF34-~ CO2Me S Me -S OEt OEt 4-CF3 H CO2Me S Me S OEt OEt ~ ' .. - . ~ : : : ................. . ~ - : , . .:........ . ..
, .: . . - , :: . - . :
Z~Q~65 ~1 R2 B V R8 Y y Rlo Y ~11 _ _ 4-CF35-9r ~ O tBu O OEt OEt 4-C15-8r H O tBu O OEt OEt 4-8r 5-Br N O tBu O OEt OEt 4-OCF35-Br H O tBu O OEt OEt 4-CF35-Cl H O tBu O OEt OEt 4-C15-Cl H O tBu O OEt OEt 4-Br 5-Cl H O tBu O OEt OEt 4-CF3 s-CF3 ~ o ti3u O OEt OEt 4-CF34-F H O tBu O OSt OEt 4-CF3 H H O tBu O OEt OEt 4-CF35-Br CO2Me O tBu O OEt OEt 4-CF35-Cl CO2Me O tBu O OEt OEt 4-CF35-CF3 CO2Me O tBu O OEt OEt 4-CF34-F CO2Me O tBu O OEt OEt 4-CF3 N CO2Me O tBu O OEt OEt 4-CF35-Cl H S tBu O OEt OEt 4-C15-Cl H S tBu O OEt OEt 4-Br S-Cl H S tBu O OEt OEt 4-CF35-Br N S tBu O OEt OEt 4-CF35-F H S tBu O OEt OEt 4-CF34-Cl H S tBu O OEt OEt 4-CF34-F H S tBu O OSt OEt 9-CF3 H H S tBu O OEt OEt 4-CF35-Cl CO2Me S tBu O OEt OEt 4-CF3 S-BI CO2Me S tBu O OSt OEt 4-CF35-F CO2Me S tBu O OEt OEt 4-CF34-Cl CO2Me S tBu O OEt OEt 4-CF34-F CO2Me S tBu O OEt OEt 4-CF3 H CO2Me S tBu O OEt OEt ' 2C~
Rl R2 ~ V R8 Y ' Y Rlo Y Rll 4-CF35-Br H O tBu O -OCH2CtMe~2CH2O-4-C15-Br ~ O t8u O -OCH2C(Me)2CH2O-4-Br 5-Br H O tBu O -OCH2C(Me)2cH2O-4-OCF35-8r H O tBu O -OCH2C(Me)2CH2O-4-CF35-Cl H O tBu O -OCH2C(Me)2CH2O-4-C15-Cl H O tBu O -OCH2C(Me)2CH2O-4-9r S-C~ H O tBu O -OCH2C(Me)2CH2O-9-CF35-CF3 H O t8u O -OCH2C(Me)2CH2O-4 CF34 F H O tBu O -OCH2C(Me)2CH2o_ 4-CF3 H H O tBu O -OCH2C(Me)2CH2O-4-CF35-Br CO2Me O tBu O -OCH2C(Me)zCH2O-4-CF35-Cl CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF35-CF3 CO2Me O t8u O -OCH2C(Me)2CH2O-4 CF34 ~ CO2Me O tBu o -OCH2C(Me)2CH2O-4-CF3 H CO2Me O tBu O -OCH2C(Me)2CH2O-4-CF35-Cl H S tBu O -OCH2C(Me)2CH2O-q-C15-Cl H S tBu O -OCH2C(Me)2CH2O-4-Br 5-Cl H S tBu O -OCH2C(Me)2CH2O-4-CF35-Br H S tBu O -OCH2C(Me)2CH2O-2S 4-CF35-F H S tBu O -OCH2C(Me)2CH2O-4-CF34-Cl H S tBu O -OCH2C(Me)2CH2O-4-CF34-F ~ S tBu O -OCH2C(Me)2CH2O-4-CF3 H H S tBu o -OCH2C(Me)2CH2O-4-CF35-Cl CO2Me S tBu O -OCH2C(Me)2CH2O-3~ 4-CF35-Br CO2Me S t8u O -OCH2C(Me)2CH2O-4-CF35-F CO2Me S tBu O -OCH2C(Me)2CH2O-4-CF34-Cl CO2~e 5 tBu O OCH2C(Me)2C~20 4-CF34-F CO2Me S tBu O -OCH2C(Me)2CH2O-4-CF3 H CO2Me S tBu O -OCH2C(Me)2~2 .
21~B~65 ~ble 11 . -5 . j~
4 `~
N-N ~
~ N ,y, .
O S-N-P-Y Rl, 1 1 :
R~Rlo :
. :
Rl R2 B V R8 Y Rlo Y Rll .
. . .
4-CF3 5-Br H O iPr O Et OEt 4-C1 5-Br H O iPr O Et OEt ,,~:-4-Br 5-Br H O iPr O Et OEt - 4-OCF3 5-Br H O iPr O Et OEt 4-CF3 5-Cl H O iPr O Et OEt ..
4-C1 5-Cl H O iPr O Et OEt : -4-Br 5-Cl H O iPr O Et OEt 4-CF3 5-CF3 H iPr O Et OEt 4-CF3 4-F H O iPr O Et OEt ~:;
4-CF3 H H O iPr O Et OEt -:
4-CF3 5-Br CO2Me iPr O Et OEt 4-~F3 5-Cl CO2Me iPr O Et OEt .
': -,:
,, . ,: . : : .
6~
Rl R2 B V ~8 Y' Rlo Y R
4-CF35-CF3 CO2Me O iPr O Et OEt 4-CF34 F CO2Me iPr O Et OEt 4-CF3 H CO2Me iPr O Et OEt 4-CF35-Cl H S iPr O Et OEt 4-C15-Cl ~ S iPr O Et OEt 4-Br 5-Cl H S iPr O Et OEt 4-CF35-8r H S iPr O Et OEt 4-CF35-F H S iPr O Et OEt 4-CF34-Cl H S iPr O Et OE t 4-CF34-F H S iPr O Et OEt 4-CF3 H H S iPr O Et OEt 4-CF35-Cl CO2Me S iPr O Et OEt 4-CF35-Br CO2Me S iPr O Et OEt 4 CF35 F CO2Me S iPr O Et OEt 4-CF34-Cl CO2Me S iPr O Et OEt 4-CF34-F CO2Me S iPr O Et OEt 4-CF3 H CO2Me S iPr O Et OEt 4-CF35-Br H O iPr O Et O-iPr 4-C15-Br H O iPr O Et O-iPr 4-Br 5-Br H O iPr O Et O-iPr 4-OCF35-Br H O iPr O Et O-iPr 4-CF35-Cl H O iPr O Et O-iPr 4-C15-Cl H O iPr O Et O-iPr 4-Br 5-Cl H O iPr O Et O-iPr 4-CF35-CF3 H iPr O Et O-iPr 4-CF34-F H O iPr O Et O-iPr 4-CF3 H N O iPr O Et O-iPr 4-CF35-Br CO2Me iPr O Et O-iPr 4-CF35-Cl CO2Me O iPr O Et O-iPr 4-CF35-CF3 CO2Me o iPr O Et O-iPr 4-CF34-F CO2Me iPr O Et O-iPr 4-CF3 H CO2Me iPr O Et O-iPr ~ . .
, , . . . ... , ,, ~, . , ,,, .. , . . .. . , . ; .... -- . - .
t6~
Rl R2 B V R8 Y Rlo Y Rll_ .
4-CF35-Cl H S iPr O Et O-iPr 4-C15-Cl H S iPr O Et O-îPr 4-Br 5-Cl H S iPr O Et O-iPr 4-CF35-Rr H S iPr O Et O-iPr 4-CF35-F H S iPr O Et O-iPr 4-CF34-CI H S iPr O Et O-iPr 4-CF34-F H S iPr O Et O-iPr ., 4-CF3 H H S iPr O Et O-iPr 4-CF35-Cl CO2Me S iPr O Et O-iPr 4-C~35-~r CO2~e S iPr O Et O-iPr 4-CF35-F CO2Me S iPr O Et O-iPr 4-CF34-Cl CO2Me S iPr O Et O-iPr 4-CF34-F CO2Me S iPr O Et O-iPr 4-CF3 H CO2Me S iPr O Et O-iPr , .
4-CF35-Br H O iPr O Et OPh 4-C15-Br H O iPr O Et OPh 4-Pr 5-~r H O iPr O Et OPh 4-OCF35-Pr H O iPr O Et OPh 4-CF35-Cl H O iPr O Et OPh 4-C15-Cl H O iPr O Et OPh 4-~r 5-Cl H O iPr O Et OPh : .
q-C~35-CF3 H o iPr O Et OPh 4-CF34-F H O iPr O Et OPh 4-CF3 H H O iPr O Et OPh 4-CF35-Br CO2Me O iPr O Et OPh 4-CF35-Cl CO2Me iPr O Et OPh 4-CF35-CF3 CO2Me O iPr O Et OPh 4-CF34-F CO2Me O iPr O Et OPh ;.
4-C~3 H CO2Me O iPr O Et OPh 4-CF35-Cl H S iPr O Et OPh 4-C15-Cl H S iPr O Et OPh , .~ . :- .: ,: : .:
2~Q~6S
llB
Rl R2 B V R8 Y' Rl~ Y R
9-Br 5-CI H S iPr O Et OPh 4-CF35-Br H S iPr O Et OPh 4-CF35-F H S iPr O Et OPh 4-CF34-Cl H S iPr O E~ OPh 4-CF34-F H S iPr O Et OPh 4-CF3 H H S iPr O Et OPh 4-CF35-Cl C02Me S iPr O Et OPh 4-CF35-9r CO2Me S iPr O Et OPh 4-C~35-F CO2Me S iPr O Et OPh 4-CF34-Cl C02~e S iPr O Et OPh 4-CF34-F CO2Me S iPr O Et OPh 4-CF3 H CO2Me S iPr O Et OPh 4-CF35-Br H O iPr O Ph OEt 4-C15-~r H O iPr O Ph OEt 4-Br 5-Br H O iPr O Ph OEt 4-OCF35-Br N O iPr O Ph OEt 4-CF35-Cl H O iPr O Ph OEt 4-C15-Cl H O iPr O Ph OEt 4-Br 5-Cl H O iPr O Ph OEt 4-CF35-CF3 H o iPr O Ph OEt 4-CF34-F H O iPr O Ph OEt 4-CF3 N H O iPr O Ph OEt 4-CF35-Br CO2Me O iPr o Ph OEt 4-CF35-Cl CO2Me O iPr O Ph OEt 4-CF35-CF3 CO2Me O iPr O Ph OEt 4-CF34-F CO2Me iPr O Ph OEt 4-CF3 H . CO2Me O iPr O Ph OEt 4-CF35-CI B S iPr O Ph OEt 4-C15-Cl H S iPr O Ph OEt 4-~3r 5-Cl H S iPr O Ph OEt 4-CF35-Br H S iPr O Ph OEt 4-CF35-F H S iPr O Ph OEt - . : . - . : - .~, : . . -, : ~ , .. . ~ : : . . . - : . . :. ., -: . , ZC~:IQ~65 Rl R2 B V ~8 Y' Rl~ Y R
4-CF34-Cl H S iPr O Ph OEt 4-CF34-F N S iPr D Ph OEt 4-CF3 ~ H S iPr O Ph OEt 4-CF35-Cl C02Me S iPr O Ph OEt 4-CF35-Br CO2Me S iPr O Ph OEt 4-CF35-F CO2Me S iPr O Ph OEt 4-CF34-Cl CO2Me S iPr O Ph OEt 4-CF34-F CO2Me S iPr O P~ OEt 4-CF3 H CO2Me S iPr O Ph OEt 4-CF35-Br N O tBu O Et OEt q-C15-Br B O tBu O Et OEt 4-Br 5-Br H O t8u O Et OEt 4-OCF35-Br H O tBu O Et OEt 4-CF35-Cl H O tBu O Et OEt 4-C15-Cl H O tBu O Et OEt 4-8r S-Cl H O tBu O Et OEt 4-CF35-CF3 H O tBu O Et OEt 4-CF34-F H O tBu O Et OEt 4-CF3 H H O tBu O Et OEt 4-CF35-Br CO2Me O tBu O Et OEt 4-CF35-Cl C02Me tBu O Et OEt 4-CF35-CF3 CO2Me O tBu O Et OEt 4-CF34-F CO2Me tBu O Et OEt 4-CF3 H CO2Me O tBu O Et OEt 3 D 4-CF35-Cl H S tBu O Et OEt 4-C15-Cl H S tBu O Et OEt 4-Br 5-Cl H S tBu O Et OEt 4-CF35-Br H S tBu O Et OEt 4-CF35-F H S tBu O Et OEt 4-CF34-Cl H S tBu O Et OEt 4-CF34-F H S tBu O Et OEt ,:. ~ .', ,: . ', ': ' ' - . ' ' : , . ' . ::
: ~, . , . ' ~ ' ,, : , ' .
' ' ' . ': ~ . ' ' ' ' ' , ::
, ,' :' , : ' . " ' ' ~, 6~
Rl R2 B V RB Y' ~10 Y R
4-CF3 H H S t8u O Et . OEt 4-CF35-Cl C02Me S t8u O Et OEt 4-CF35-Br C02Me S tBu O Et OEt 4 CF35 F C02Me S tBu O Et OEt 4-CF34-Cl CO2Me ~ tBu O Et OEt 4 CF34 F COzMe S tBu O Et OEt 4-CF3 H C02Me S tBu O Et OEt 4-C15-Br H O iPr S Et O-iPr 4-Br 5-Br H O iPr S Et OPh 4-OCF35-Br H O iPr S Ph OEt 4-CF3 S-Cl H O iPr S Ph O-iPr 4-C15-Cl H O iPr S Ph OPh 4-Br 5-Cl H O tBu S Et OEt 4-CF35-CF3 H o tBu S Et O-iPr 4-CF34-F H O tBu S Et OPh 4-CF~ H H O tBu S Ph OEt 4-CF35-Br CO2Me O tBu S Ph O-iPr .:
4-CF35-Cl CO2Me O tBu S Ph OPh q-CF35-Br H S iPr S iPr OEt 4-CF35-F H S iPr S iPr O-iPr 4-CF34-Cl H S iPr S iPr OPh 4-CF34-F H S iPr S nPr OEt 4-CF3 H H S iPr S nPr O-iPr 4-CF35-Cl CO2Me S iPr S nPr OPh 4-CF35-Br CO2Me S tBu S Me OEt 4-~F35-F CO2Me S tSu S Me O-;Pr 4-CF34-Cl CO2Me S tBu S Me OPh 4-CF34-F CO2Me S tBu S Me O-~ec-Bu 4-CF3 H C02Me S tBu S Me O-nPr : .
.' ' ., ~ . , . . . .,., . .. ~., . , . ,. , , ~, , , , ,, "
,: - . . - :: - : . . : .. . - :, ~.
XC~ 165 T~bl~_12 U-N ~ R~
~, ,, ' S-P-ORlD
ORl 1 ~'.
Rl R2 BV Rlo Rll 4-CF3 5-Br H O Et Et 4-C1 5-Br HO Et Et 4-Br 5-Br HO Et Et 4-OCF3 5-Br H O Et Et ::~
4-CF3 5-Cl H O Et Et 4-C1 5-Cl HO Et Et 4-Br 5-Cl HO Et Et 4-CF3 5-CF3 H Et Et 4-CF3 q-F HO Et Et 4-CF3 H HO Et Et ~
4-CF~ 5-Br CO2Me O Et Et ~.
4-CF3 5-Cl CO2Me O Et Et '; -' ,: . , "
~ ., ~ , . . . ..
2~ 65 Rl R2 8 V Rlo Rll 4-CF3 5-CF3 C02Me O Et Et 4-CF3 4-F C02Me O Et Et 4-CF3 ~ C2Me O Et Et 4-CF3 5-Cl H S Et Et 4-C1 5-Ci H S Et Et 4-8r 5-Cl H S Et Et 4-CF3 5-Br H S Et Et 4-CF3 S-F H S Et Et 4-CF3 4-Cl H S Et Et 4-CF3 4-F H S Et Et 4-CF3 H H S Et Et 4 CF3 5 Cl C02Me S Et Et 4-CF3 5-Br C02Me S Et Et 4-CF3 S-F C02Me S Et Et 4-CF3 4-Cl C02Me S Et Et 4-CF3 4-F C02Me S Et Et 4-CF3 H C02Me S Et Et 2~ 65 Table 13 '-~
~ N
O S-N-R~
Rl R2 B V R8 R12 : , 4-CF3 5-Br H O nBu nBu 4-Cl S-Br H O nBu nBu 4-Br 5-Br H O nBu nBu 4-OCF3 5-Br H O nBu nBu 4-CF~ 5-Cl H O nBu nBu 4-C1 5-Cl H O nBu nBu 4-Br 5-Cl H O nBu nBu 4-CF3 S-CF3 H nBu nBu 9-CF3 4-F H O nBu nBu 4-C~3 H B O nBu ~Bu 4 CF3 S-Br CO2Me O ~Bu nBu 4-cr3 5-Cl CO2Me O DBu DBu -, 9-CF3 5-CF3 CO2Me O nBu nBu .
:
. .
., . .~ . . . . ... . . . .. . . . .. . .
.: .: : , .: . . - ~ . , .. , .: - ., . ~ . - . . : . ,-2~ iS
Rl R2 B V R8 R12 4-CF34-F CO2Me O nBu nBu 4-CF3 H CO2Me O ~Bu nBu 4-CF35-Cl H S nBu nBu 4-C15-Cl H S nBu ~Bu 4-Br S-Cl H S nBu nBu 4-CF35-Br H S nBu nBu 4-CF35-F H S n9u nBu 4-CF34-Cl ~ S ~Bu ~Bu 4-CF34-F H S nBu nBu lS 4-CF3 H H S nBu nBu 4-CF35-Cl C02Me S nBu nBu 4-CF35-Br CO2Me S ~Bu nBu 4-CF35-F CO2Me S nBu nBu 4-CF34-Cl CO2Me S nBu nBu 4-CF34-F CO2Me S nBu nBu 4-CF3 H CO2Me S nBu nBu 4-CF35-Br H O -CH2CH2CH2cH2~H2-4-Cl S-B~ H O -CH2CH2CH2cH2cH2-4-Br 5-Br H O -CH2CH2CH2c~2cH2-4-OCF35-Br H O -CH2CH2CH2cH2 Q2-4-CF35-C~ H O -CH2CH2CH2cH2cH2 4-Cl S-Cl H O -CH2CH2CH2cH2cH2-4-Br 5-Cl H O -CH2CH2CH2cH2cH2-3.3 -CH2CH2CH2cH2cH2-4-CF34-~ H O -CH2CH2CH2cH2c~2-4-CF3 H N O -CH2CH2CH2cH2cH2-4-CF35-Br CO2Me O -CH2CH2CH2cH2cH2 4-CF35-Cl CO2Me O -CH2CH2CH2c82cH2 4-CF3 5-CF3 CO2Me O -CH2CH2CH2cH2cH2 4-CF3 4-F CO2Me -CH2CH2CH2cH2cH2 4-CF3 H CO2Me O -CH2CH2CH2cH2cH2-4-CF3 5-Cl H S -cN2cH2cH2cH2cH2 , .,.......... : i - - .... - 1~
3Q~6~
Rl R2 B V R8 R12 4-C15-Cl H S -CH2CH2CH2cH2cB2-4-Br 5-Cl H S -CH2CH2CH2CH2CH2-4-CF35-Br H S -CH2CH2CH2cH2cH2-4 CF35 F H S -CH2CH2CH2cH2cH2-4-CF34-Cl H S -CH2CH2CH2cH2cH2-4-CF34-F H S -CH2CH2CH2cH2cH2-4-CF3 H H S -CH2CH2CH2cH2cH2-3 CO2Me S -CH2CH2CH2CH2CH2-4-CP35-Br C02Me S -CH2CH2CH2CH2CH2-4 CF35 F C02Me S -CH2CH2CH2CH2CH2-4-CF34-Cl C02Me S -CH2CH2CH2cH2cH2-4-CF34-F CO2Me S -CH2CH2CH2CH2CH2-4-CF3 H CO2Me S -CH2CH2CH2CH2CH2-4-CF35-9r H O -CH2CH20CH2cH2-4-C15-Br H O -CH2CH20CH2cH2-4-Br 5-Br H O -CH2CH20C~2cH2 4-OCF35-Br H O -CH2cH2cH2cH2-4-CF35-Cl H O -cH2cH2ocH2cH2 4-C15-Cl H O -CH2CH20CH2cH2-4-Br 5-Cl H O -CH2CH20CH2cH2-4-CF35-CF3 H O -CH2cH2cH2cH2 4-CF34-F H O -CH2CH20CH2cH2-4-CF3 H H O -cH2cH2ocH2cH2 4-CF35-Br CO2Me -CH2CH20CH2cH2-4-CF35-Cl CO2Me O -CH2cH2cH2cH2-4-CF35-CF3 CO2Me O -CH2cH2cH2cH2 4-CF34-F CO2Me -cH2cH2ocH2cH2 4-CF3 H CO2Me O -CH2cH2cH2cH2-4-CF35-Cl H S -CH2C~20CH2cH2-4-C15-Cl H S -cH2cH2ocH2cH2 4-Br 5-Cl H S -cN2cH2ocH2cH2-4-CF35-~r H S -CH2CH20C~2cH2-4 CF35-F H S -cH2cH2ocH2cH2 ... . -- ~ ' ' , Q~65 hl R2 8 V R8 R12 4-CF34-Cl ~ S -CH2cH2cH2cH2-4 C~34-F H S -CH2CH20CH2cH2 4-CF3 H H S -C92CH20C~2CH2 4-CF35-Cl CO2Me S -CH2cH2cH2cH2-4-CF35-Br C2Me S -CH2cH2cH2cH2-4 CF35 F C02Me S -CH2cH2cH2cH2-4-CF34-Cl CO2Me S -CH2cH2cH2cH2-4-CF34-F C~2Me S -CH2CH20CB2c~2-4-CF3 H C02Me S -CH2CH20CH2CH2-4-CF35-Br H O -CH2CHMeOCHMeCH2-4-C15-Br H O -CH2CHMeOCHMeCH2-4-Br 5-Br H O -CH2CHMeOCHMeCH2-4-OCF35-Br H O -CH2CNMeOCHMeCH2-4-CF35-Cl H O -CH2CHMeOCHMeCH2-4-C15-Cl H O -CH2CHMeOCHMeCH2-4-Br 5-Cl H O -CH2CHMeOCHMeCH2-4-CF35-CF3 H O -CH2CHMeOCHNeCH2-4-CF34-F H O -CH2CHMeOCHMeCH2-4-CF3 H H O -CH2CHMeOCHMeCH2-4-CF35-Br CO2Me O -CH2CHMeOCHMeCH2-4-CF35-Cl C02Me -CH2CHMeOCHMeCH2-4-CF35-CF3 CO2Me O -CH2CHMeOCHMeCH2-4-CF34-F CO2Me O -CH2CHMeOCHMeCH2-4-CF3 H CO2Me O -CH2CHMeOCHMeCH2-4-CF35-Cl H S -CH2CHMeOCHMeCH2-4-C15-C~ ~ S -CH2CNMeOCHMeCH2-4-Br 5-Cl H S -CH2CHMeOCHMeCH2-4-CF35-Br H S -CH2CHMeOCHMeCN2-4 CF35 F H S -CH2CHMeOC~MeCH2-4-CF34-Cl H S -CH~CHMeOCHMeCH2-4-CF34-F H S -CH2CHMeOCHMeCH2-. . . : . , :. : , ~ " : : : :: ; .
-2C~ 5 _ 1 R2 B V R8 R12 4-CF3 H H S -CH2Cl~eOCHMeCB2-4-CF35-Cl CO2Me S -CH2CHMeOCKMeCH2-4 CF359r CO2Me S -CH2CHMeOCHMeCH2-4-CF35-F CO2Me S -CH2CHMeOCHMeCH2-4-CF34-Cl c~2Me S -CH2CHMeOCHMeCH2-4-CF34-F CO2Me S -CH2CHMeOCHMeCH2-4-CF3 H C02Me S -CH2CHMeOCHMeCH2-4-CF35-Br H O ~t ~yclo-C
4-C15-Br H O Et cyclo-C6H
15 4-Br 5-i3r H O Et cyclo-C6H
4-OCF35-i3r H O Et cyclo-C6H
4-CF35-Cl H O Et cyclo-C6H
4-C15-Cl H O Et cyClo-c6 4-Br 5-Cl H O Et cyclo-C6H
20 4-CF35-CF3 H o Et cyClo-c6 4-CF34-F H O Et c 4-CF3 H H O Et cyClo-c6 4-CF35-Br CO2Me Et cycl3 4-CF35-Cl C02Me Et c 25 4-CF35-CF3 CO2Me O Et CYC1-4-CF34-F CO2Me O Et cyClo-c6 4-CF3 H CO2Me O Et cyclo-c6 4-CF35-Cl H S Et c 4-C15-Cl H S Et c 30 4-Br 5-Cl H S Et cyclo-C6H
4-CF35-Br H S Et cycl~-c6 4-C~35-F H S Et CYC1~
4-CF34-Ci H S Et CYClo-C6Hl 4-CF34-F H S Et CYC1-C6Nl 3S 4-CF3 H H S Et cyclo-C6H
4-CF35-Cl CO2Me S Et CYC1~
...
. .
- "
.; ., .
:. : ~ ~: : :: . . . ..
Z~ 6S
Rl ~2 B V R8 R12 4-CF35-Br CO2Me S Et ~yclo-C6H
4-CF35-F CO2Me S Et ~YCl-4-CF34-Cl CO2Me S Et c 4-CF34-F CO2Me S Et cyclo-C6H
4-CF3 H CO2Me S Et cyC10-c6Hll 4-CF35-Br H O iPr CH2CH2C2Et 4-Cl S-Br H O iPr CN2CH2C2Et 4-Br 5-Br H O iPr Q2CH2CO2Et 4-OCF35-Br H O iPr CH2CH2C2Et 4-CF35-Cl H O iPr CH2CH2C2Et 4-Cl S-Cl H O iPr CH2CH2C02Et 4-Br 5-Cl H O iPr CH2CH2C~2Et 4-CF35-CF3 H O iPr CH2CH2C2Et 4 CF34 F H O iPr CH2CH2C2Et 4-CF3 H H O iPr CHzCH2CO2Et 4-CF35-Br CO2Me iPr CH2CH2C02Et 4-CF35-Cl CO2Me O iPr CH2CH2C02Et 4-CF35-CF3 CO2Me O iPr CH2CH2C2Et 4-CF34-F CO2Me O iPr CH2CH2CO2Et 4-CF3 H CO2Me O iPr CH2CH2C2Et 4-CF35-Cl H S iPr CH2CH2C2Et 4-C15-Cl H S iPr CH2CH2CO2Et 4-Br S-Cl H S iPr CH2CH2C02Et 4-CF35-Br H S iPr CH2CH2C2Et 4-CF35-F H S iPr CH2CH2C2Et 4-CF34-Cl H S iPr CH2CH2C2Et 4-CF34-F H S iPr CH2CH2CO2Et 4-CF3 H H S iPr CH2CH2C2Et 4-CF35-Cl C02Me S iPr CN2CN2C2Et 4-CF35-Br CO2Me S iPr CH2CH2CO2Et 4-CF35-F CO2Me S iPr CH2CH2C2 : .'~
. , . - ,-: ., ~ ,, ... . , , . ,. j, :,, . : .
. : . ,::: ,,: " , , .. . , .:, ,. ,. .. : . : ... ::. ~ ,, .~ . . : . . : . . . :
, . ','' ' ~ ' ' ' ' ' ';', ' , '.' ' ', ',' " ''," '" ". ,' '' ' ' "' ' ' .' ,', " ''"' ' ,. "' , ' ', ' 2~3~65 Rl R2 B V RB R12 .
4 CF3 4 Cl C2Me S iPr CH2CH2CO2Et ..
4-CF3 4-F CO2Me S iPr CH2CH2C2Et 4-CF3 H CO2Me S . iPr CH2CH2C2Et , ': . ' . ', ';, ' ' . ' . ' ' . . . , ' ' , ~. ., ': ~ ' . ` , " . . ' , " , : " ~ . ' , ' ' ' .. , .. : .. ', . .'.. , ., ', ,'; . ,- . ' ' .. '', ' ' : . .... ~ " ', . ' '.'. ' ' :' " . ' ' . ' ', ,, .'.'. ', : ' , , ' : ,"' ' , :' .. ' ' .'.'~ . ', ' ' '.' .,: ' ' " . ', . "
f -Z~ Q~6~
130 ~:~
Table 14 R~ ~ N-N ~ R
~ N
S-SRlD
:.
Rl R2 B V Rlo . -4-CF3 5-Br H O tBu 4-C1 5-Br H O tBu 4-Br 5-Br H O tBu 4-OCF3 5-Br H O tBu 4-CF3 5-Cl H O tBu ~ ~' 4-C1 5-Cl H O tBu ;
4-Br 5-Cl H O tBu 4-CF3 5-CF3 H O tBu 4-CF3 4-F H O tBu 4-CF3 H H O tBu 4-CF3 5-Br CO2Me tBu 4-CF3 5-Cl CO2Me O tBu 4-CF3 5-CF3 CO2Me O tBu .
4-CF3 4-F CO2Me tBu .- . . . . - -- .. .. . .. . . . . .. . . . .. . . ., . . . . . . , . . -. ,. : - .
.,.. , . ... ., , . ~ , i , ; - , . .. , .,:, . . - . - : - . -2~3Q,~6~
_Rl R2 B V Rlo 4-CF3 H C02Me O tBu 4-CF35-Cl H S tBu 4-C15-Cl H S tBu 4-Br 5-Cl H S t8u :;
4-CF35-Br H S tBu ::
4-CF35-F H S tBu 4-CF34-Cl H S tBu 4-CF34-~ H S tBu 4-CF3 H H S tBu 4-CF35-Cl CO2Me S tBu 4-CF35-Br CO2Me S tBu 4-CF35-F CO2Me S t8u 4-CF34-Cl CO2Me S tBu 4-CF34-F CO2Me S tBu 4-CF3 H CO2Me S tBu 4-Br 5-Cl H S 6ec-Bu 4-CF35-Br H S sec-Bu 4-CF35-F H S sec-Bu 4-CF34-Cl H S rec-Bu 4-CF34-F H S cec-Bu 4-CF3 H H S ~ec-Bu 4-CF35-C~ CO2Me S ~ec-Bu 4-CF35-Br CO2Me S bec-Bu 4-CF35-F CO2Me S ~ec-Bu 3û 4-CF34-Cl CO2Me S cec-Bu 4-CF34-F CO2Me S ~ec-Bu 4-CF3 N CO2Me S ~ec-8u 4-CF35-Br H O Ph 4-C15-Br H O Ph 4-Br 5-i3r H O Ph 4-OCF35-Br H O Ph ~-:
.
' .
.-. . . , . : .: . - ~ . . -:: - -,' - : - . ~ . , . . :: ' - - . .: ::: : : ~ , :
Z~ 65 Rl R2 B V Rlo - .
4-CF3 5-Cl ~ O Ph 4-Cl S-Cl H O Ph 4-Br 5-Cl H O Ph 4-CF3 5-CF3 H o Ph 4-CF3 4-F H O Ph 4-CF3 H H O Ph ~-CF3 S-Br CO2Me Ph 4-CF3 5-Cl CO~Ne O Ph 4-CF3 5-CF3 CO2Me O Ph 4-CF3 4-F C2Me O Ph 4-CF3 H CO2Me Ph 4-CF3 5-Cl H S Ph 4-Cl S-Cl H S Ph ~.
4-Br 5-Cl H S Ph 20 4-CF3 5-Fr H S Ph 4-CF3 5-F H S Ph 4-CF3 4-Cl H S Ph 4-CF3 4-F H S Ph 4-CF3 H H S Ph 25 4-CF3 5-Cl CO2Me S Ph 4-CF3 S-Br CO2Me S Ph .
4-CF3 5-F CO2Me S Ph 4-CF3 4-Cl CO2Me S Ph 4 CF3 4-F CO2Me S Ph :;
4-CF3 H C02Me S Ph 4-CF3 5-Br H O 4-Cl-Ph 4-C1 5-Br H O 4-Cl-~h 4-Br 5-Br H O 4-Cl-Ph 4-OCF3 5-Br H O 4-Cl-Ph 4-CF3 5-Cl H O 4-Cl-Ph 4-C1 5-Cl H O 4-Cl-Ph , . -.: - . ~ . . - : . - .
Z~ 65 133 :
Rl R2 B V Rlo -4-Br 5-Cl H . 0 4-Cl-Ph 4-CF35-CF3 H 0 4-Cl-Ph 4-CF34-F H 0 4-Cl-Ph 4-CF3 ~ H 0 4-Cl-Ph 10 4-CF35-~r C02Me 4-Cl-Ph 4-CF35-Cl C02Me O 4-Cl-Ph 4-CF35-CF3 C02Me O 4-Cl-Ph 4-CF34-F C02Me 4-Cl-Ph 4-CF3 ~ C02Me g-Cl-Ph 15 4-CF35-Cl H S 4-Cl-Ph 4-C15-Cl H S 4-Cl-Ph . , 4-Br 5-Cl H S 4-Cl-Ph 4-CF35-Br H S 4-Cl-Ph 4-CF35-F H S 4-Cl-Ph 20 4-CF34-Cl H S 4-Cl-Ph 4-CF34-F H S 4-Cl-Ph 4-CF3 H H S 4-Cl-Ph 4-CF35 Cl C02Me S 4-Cl-Ph 4-CF35-Br C02Me S 4-Cl-Ph 25 4-CF35-F C02Me S 4-Cl-Ph 4-CF34-Cl COzMe S 4-Cl-Ph 4-CF34-F C02Me S 4-Cl-Ph 4-CF3 H C02Me S 4-Cl-Ph . ,: ' ' - :,, .. : .: . : . - : . : ,: - ~., . :
.. ~ . . . .
~ble 15 11 5~RI3 ~ N O
S -N ~ `.
~ Rg R1 R R13a R13b V R8 ~9 ~ :
4-CF3 5-F Me Me S Me OEt 4-CF3 5-Cl Me Me S Me OEt 4-CF3 4-F Me Me S Me OEt 4-CF3 5-Br Ph H O Me OEt '. -4-CF3 5-Br C02Me H O Me OEt 4-CF3 5-Br Me ~e O Me OEt 4-CF3 5-Cl Me Me O Me OEt 4-CF3 5-F Me Me S Me O-nBu l~ .
4-CF3 5-C1 Me Me S Me O-nBu 4-CF3 4-~ Me Me S Me O-DBu -4-CF~ S-Br Pb H O Me O-~Bu .
4-CF3 5-Br C02Me H O Me O-n8u 4-CF3 5-~r Me Me O Me 0-~9u 3~ ~-CF3 5-Cl Ne Me O Me O-nBu : .
''' '". ' ~'.
Z~!0~6~
Rl R2 pl3a pl3b V R~ Rg 4-CF35-F Me Me S Me 0-nHexyl 4-CF35-Cl Me Me S Me 0-nHe~yl 4-CF34-F Me Me S Me 0-nHe~yl 4-C~35-Br Ph H 0 Me 0-nHexyl 10 4-CF35-Br C02Me H 0 Me 0-nHe~yl 4-CF35-Br Me Me 0 Me 0-nHe~yl 4-CF35-Cl Me Me 0 Me 0-nHe~yl 4-CF35-F Me Me S Me 0-~ec-Bu 4-CF35-Cl Me Me S Me 0-~ec-Bu 15 4-CF34-F Me Me S Me 0-~ec-Bu 4-CF35-Br Ph H 0 Me 0-6ec-Bu 4-CF35-Br C02Me H 0 Me 0-6ec-Bu 4-CF35-Br Me Me 0 Me 0-6ec-Bu 4-CF35-Cl Me Me 0 Me 0-sec-Bu 20 4-CF35-F Me Me S Me 0-iPr 4-CF35-Cl Me Me S Me 0-iPr 4-CF34-F Me Me S Me 0-iPr 4-CF35-Br Ph H 0 Me 0-iPr 4-CF35-~r C02Me H 0 Me 0-iPr 25 4-CF35-Br Me Me 0 Me 0-iPr 4-CF35-Cl Me Me 0 Me 0-iPr 4 CF35-F Me Me S Me OCH2CH20Et 4-CF35-Cl Me Me S Me OCH2CH20Et 4-~F34-F Me Me S Me 0CH2CH20Et 4-CF35-Br Ph H 0 Me OCH2CH20Et 4-CF35-~r C02Me H 0 Me OCH2CH20Et 4-CF35-Br Me Me 0 Me OCH2CH20Et 4-CF35-Cl Me Me 0 Me OCH2CH20Et 4-CF35-F Me Me. S Me F
4-CF35-Cl Me Me S Me F
4-CF34-F Me Me S Me F
';, ':
' ':
, - . ~ : : -:: . . ~ , . , .. . ~, , .. . . .-:
~ . , . :~, : . :: : . . -~C~0~65 Rl R2 pl3a pl3b V RB Rg 4-CF3 5-Br Ph H O Me F
4-CF3 5-Br C02Me H O Me F
4-CF3 5-~r ~e Me O Me F ~.
4-CF35-Cl ~e Ne O Me F
4-CF35-F Me Me S Me NMe2 4-CF3 5-Cl Me Me S Me NMe2 4-CF34-F Me Me S Me NMe2 4-CF3 5-Br Ph N O Me NMe2 4-CF3 S-}lr C02Me H 0 Me NMe2 4-CF3 5-~r Me Me O Me NMe2 4-CF3 5-Cl Me Me O Me NMe2 .
4-CF3 5-F Me Me S Et O-iPr ' 4-CF3 5-Cl Me Me S Et O-iPr 4-CF34-F Me Me S Et O-iPr : .:
4-CF3 5-Br Ph H O Et O-iPr 4-CF3 5-Br C02Me H O Et O-iPr , i .
4-CF3 5-Br Me Me O Et O-iPr 4-CF3 5-Cl Me Me O Et O-iPr .: .
4-CF35-F Me Me S iPr OEt .
4-CF35-Cl Me Me S iPr OEt 4-CF34-F Me Me S iPr OEt 4-CF3 5-Br Ph H O iPr OEt 4-CF3 5-Br C02Me H O iPr OEt 4-CF35-Br Me Me O iPr OEt 4-CF 5-Cl Me Me O iPr OEt 4-CF35-F Me Me S ~Pr OCH2CF3 4-CF35-Cl Me Me S ~Pr OCH2CF3 ,.
4-CF34-F Me Me S iPr OCH2CF3 ;
4-CF3 5-Br Ph H O lPr OCH2CF3 4-CF3 5-Br C02Me H O iPr OCHzCF3 4-CF3 5-Br Me Me O iPr OCH2CF3 ~:~
- , . .. . .
. . : ~
2~ L6~;
Rl R2 R 3a R b V R8 Rg S
4-CF3 5-Cl Me Me O iPr OCN2CF3 4 CF3 S F Me Me S ~Pr OCH2CO2Me 4-CF3 5-Cl Me Me S iPr OCH2CO2Me 4-CF3 4-F Me Me S iPr OCH2CO2Me 4-CF3 5-Br Ph H O iPr OCH2CO2Me 4-CF3 5-9r CO2Ne H O iPr OCH2CO2Me 4-CF3 S-Br Me Me O iPr OCH2CO2Me 4-CF3 5-Cl Me Me O iPr OCH2CO2Me ', ..
I~ble 16 R2 ~R3 .:~
~ ' ;' '' ~' S~ ~
~ ~9 Rfl Rl R2 R3 RB Rg 4-CF3 4-Cl H Me OEt 4-C1 4-Cl H Me OEt 4-B~ 4-Cl H Me GEt 4-OCF3 4-Cl H Me OEt 4-OCF2H 4-Cl H Me OEt ' 2 ( )2 4-Cl ~ Me OEt 4-CF3 4-F H Me OEt 4-C1 4-F H Me OEt 4-Br 4-F B Me OEt 4-OCF3 4-F H Me OEt 4-OC~2H 4-F H Me OEt 3,4-CH2C(Me~2O 4-F H Me OEt ~1 R2 R3 ~8 Rg -. :
4-CF3 4-OCF2H H Me OEt 4-C1 4-OCF2H H Me OEt 4-8r 4-OCF2H H Me OEt 4-OCF3 4-ocF2a H Me OEt 0 4-OCF2H 4-OCF2H H Me OEt 3,4-CH2C(Me)20 4-OCF H N Me OEt 4-CF3 4-Br H Me OEt 4-CF3 4-C1 4-Cl Me OEt 4-C1 4-C1 4-Cl Me OEt 4-Br 4-C1 4-Cl Me OEt 4-OCF3 4-C1 4-Cl Me OEt 4-OCF2H 4-C1 4-Cl Me OEt 3,4-CH2C(Me)20 4-C1 4-Cl Me OEt 4-CF3 4-F 4-Cl Me OEt 4-OCF3 4-F 4-Cl Me OEt .-4-CF3 4-OCF2H 4-Cl Me OEt 4-OCF3 4-OCF2H 4-Cl Me OEt 4-CF3 4-C1 4-CN Me OEt 4-C1 4-C1 4-CN Me OEt 4-OCF3 4-C1 4-CN Me OEt 2S 4-CF3 4-F 4-CN Me OEt . .
4-OCF3 4-F 4_CN ~e OEt 4-CF3 4-C1 4-CO2Me Me OEt 4-CF3 q-Cl H Me O-n-Bu 4-OCF3 4-Cl H Me O-n-Bu 4-CF3 4-F H Me O-n-Bu 4-OCF3 4-F H . Me O-n-Bu 3,4-CH2C(Me)20 4-F H Me O-n-Bu 4-CF3 4-OCF2H H Me O-n-Bu 4-C~ 4-OCF2H H Me O-n-Bu 4-B~ 4-OCF2H H Me ' O-n-Bu - . : . . - , ,- : . :, - , , :: :: . , , . .:
- - . -, - - .. , , . : .. . .: : .
., ~ : , .. . . ..
:,. . ..
Rl R2 R3 R8 Rg . ';
4-OCF3 4-OCF2H 8 Me O-n-Bu 4-CF3 4-Br H Me O-n-13u 4-CF3 4-C1 4-Cl Me O-n-Bu 4-Sl 4-C1 4-Cl Me O-n-Bu 4-Br 4-C1 4-Cl Me O-n-Bu 4-OCF3 4-C1 4-Cl Me O-n-Bu 4-CF3 4-F 4-Cl Me O-n-Bu .
4-OCF3 4-F 4-Cl Me O-n-~u :.
4-CF3 4-OCF2R 4-Cl Me O-n-Bu 4-C1 4-OCF2B 4-Cl Me O-n-Bu 4-Br 4-OCF2H 4-Cl Me O-n-Bu 4-OCF3 4-OCF2H 4-Cl Me O-n-Bu 4-CF3 4-C1 4-CN Me O-n-Bu 4-OCF3 4-C1 4-CN Me O-n-Bu 4-CF3 4-F 4-CN Me O-n-Bu 4-OCF3 4-F 4-CN Me O-n-Bu 4-CF3 4-C1 4-C02Me Me O-n-Bu 4-CF3 4-OMe 4-Cl Me O-n-Bu 4-C1 4-OPh 4-Cl Me O-n-Bu 4-Br 4-SCF2H 4-Cl Me O-D-8U
4-OCF3 4-N02 4-Cl Me O-n-Bu 4-OCF2H 4-SMe 4-Cl Me O-n-Bu 3,4-CH2C(Me)20 4-S02Me 4-Cl Me O-n-Bu 4-CF3 4-CN 4-Cl Me O-n-Bu 4-C1 3-C1 4-Cl Me O-n-Bu 4-i3r 3-F 4-Cl Me O-n-Bu 4-OCF3 4-Me 4-Cl Me O-n-Bu 4-OCF2H 4-allyl 4-Cl Me O-n-Bu 3,4-C~2C(Me)20 4-CF3 4-Cl Me O-D-Bu 4-CF3 4-C1 4-C02Et Me 0-~-9u ~.
, . : . ., ,. - . .::
- .. . , .: - :
.
- ' - - . .
~lQlQ~65 Rl R2 R3 R8 Rg 4-C1 4-C1 4-OMe Me O-n-Bu 4-Br 4-C1 2 2 O-n-Bu 4-OCF3 4-C1 4-OCF2CF2H Me O-n-Bu 4-OCF2H 4-Cl 4-OPh Me O-n-Bu 3,4-CH2C(Me)20 4-CF3 4-CF3 Me O-n-Bu 4-CF3 4-C1 4-CF3 Me O-n-8u 4-C1 4-C1 4-Me Me O-n-Bu 4-Br 4-C1 3-Cl Me O-~-Bu 4-OCF3 4-C1 3 Br Me O-n-Bu 4-OCF2H 4-C1 4-NO2 Me O-D-BU
4-CF3 4-Cl H Me O-n-he~yl 4-CF3 4-F H Me O-n-hexyl 4-C~3 4-OCF2H H Me O-n-h~yl .
4-OCF3 4-OCF2H H Me O-n-octyl 4-CF3 4-Br H Me O-n-octyl 4-CF3 4-C1 4-Cl Me O-n-octyl `
4-C1 4-C1 4-Cl Me O-n-octyl 4-Br 4-C1 4-Cl Me O-n-octyl 4-OCF3 4-C1 4-Cl Me O-n-octyl 4-CF3 4-F 4-Cl Me O-n-decyl 4-C1 4-F 4-Cl Me O-n-decyl 4-OCF3 4-F 4-Cl Me O-n-decyl 4-CF3 4-OCF2H 4-Cl Me O-n-decyl 4-OCF3 4-OCF2H 4-Cl Me O-n-decyl 4-CF3 4-C1 4-CN Me O-n-decyl - 4-C1 4-C1 4-CN Me O-n-decyl 4-Br 9-Cl 4-~ Me O-n-decyl 4-OCF3 4-C1 4-CN Me O-n-dodecyl .~:
4-CF3 4-F 4-CN Me O-n-aodecyl 4-GCF3 4-F 4-CN Me O-n-dodecyl 4-CF3 4-C1 4-CO2Me Me O-n-dodecyl 4-CF3 4-Cl H Me O-sec-Bu 4-C1 4-Cl H Me O-sec-Bu :-. . .
,",." ,, ,, ~ "
.. .. ' ; ., . . . , . . ', . . . .. ' ' , . . , ., . ~ . ' ' ' :
ZCl(;~Q165 Rl R2 R3 R8 Rg S .
4-OCF3 4-Cl H Me O-cec-Bu 4-CF3 4-F H Me O-sec-Fu 4-OCF3 4-F H Me O-sec-Bu 4-CF3 4-OCF2H H Me O-rec-~u 4-OCF3 4-OCF2H H Me O-sec-Bu 4-CF3 4-Br H Me 0-6ec-Bu 4-CF3 4-C1 4-Cl Me O-sec-Bu 4-C1 4-C1 4-Cl Me O-sec-Bu 4-Br 4-C1 4-Cl Me O-~ec-Bu 4-OCF3 4-C1 4-Cl Me O-sec-Bu 4-CF3 4-F 4-Cl Me O-sec-Bu 4-C1 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me O-sec-Bu 4-CF3 4-OCF2H 4-Cl Me O-sec-Bu 4-OCF3 4-OCF2H 4-Cl Me O-sec-Bu 4-CF3 4-C1 4-CN Me O-sec-Bu 4-C1 4-C1 4-CN Me O-sec-Bu 4-OCF3 4-C1 4-CN Me O-sec-Bu 4-CF3 4-F 4-CN Me O-sec-Bu 4-OCF3 4-F 4-CN Me O--ec-Bu 4-CF3 4-C1 4-C02Me Me O-cec-Bu 4-CF3 4-CN 4-Cl Me O-~ec-Bu 4-C1 3-C1 4-Cl Me O-sec-Bu 4-Br 3-F 4-Cl Me O-sec-Bu 4-OCF3 4-Me 4-Cl Me O-sec-Bu 4-CF3 4-C1 4-C02Et Me O-sec-Bu 4-C1 4-C1 4-OMe Me O-cec-Bu 4-Br 4-C1 2 2 O-sec-Bu 4-OCF3 4-C1 4-OCF2CF2B Me O-sec-Bu 4-OCF2 4-C1 4-OPh ~e O-~ec-Bu 3,4-CH2C~Me)20 4-C1 4-CF3 Me O-~ec-Bu 4-CF3 4-C1 4-CF3 Me 0-6ec-Bu 4-C1 4-C1 4-Me Me O-sec-Bu . : - -. . . : . : . : . - . :.:, , .
2C~ 6~
Rl R2 R3 RB Rg .
4--Br 4-C1 3-Cl Me 0-6ec-Bu :
4-OCF3 4-C1 3-Br Me O-sec-Bu 4-OCF2H ~-Cl 4-No2 Me 0-6ec-Bu 4-CF3 4-Cl H Me O-iPr 4-OCF3 4-Cl H Me O-iPr 4-CF3 4-F H Me O-iPr 4-OCF3 4-F H Me O-iPr 4-CF3 4-OCF2N B Me O-iPr 4-OCF3 4-OCF2H H Me O-iPr 4-CF3 4-Br H Me O-iPr 4-OCF3 4-8r H Me O-iPr 4-CF3 4-C1 4-Cl Me O-iPr 4-OCF3 4-C1 4-Cl Me O-lPr 4-CF3 4-F 4-Cl Me O-iPr 4-OCF3 4-F 4-Cl Me O-iPr 4-CF3 4-C1 4-CN Me O-iPr 4-OCF3 4-C1 4-CN Me O-iPr 4-CF3 4-F 4-CN Me O-iPr 4-OCF3 4-F 4-CN Me O-iPr ~-CF3 4-Cl q-C02Me Me O-iPr 4-CF3 4-Cl H Me CH2c~2Et 4-CF3 4-F H Me OCH2CB20Et 4-CF3 4-OCF2H H Me OCH2CH20Et 4-OCF3 4-OCF2H H Me OCH2Ccl3 .:
4-CF3 4-Br H Me 2 3 ~::
4-CF3 4-C1 4-Cl Me OCH2ccl3 4-C1 4-C1 4-Cl Me OCH2CC1 4-OCF3 4-C1 9-Cl Me oCH2CC13 ,~
4-CF3 4-F 4-Cl Me ~CH2CF3 ~' 4-OCF3 4-F 4-Cl Me 2 3 4-CF3 4-OCF2H 4-Cl Me 2 3 :
Rl R2 R3 R8 Rg ::~
i-oCF3 4-OCF2H q-Cl Me CH2cF3 4-CF3 4-C1 4-CN Me 2 3 4-OCF3 4-C1 4-CN Me OCH2CO2Et 4-CF3 4-F 4-CN Me OCH2CO2Et 4-OCF3 4-F 4-CN Me OCH2CO2Et 4-C~3 4-C1 4-CO2Me Me OCH2CO2Et 4-CF3 4-Cl H Me F
4-C1 4-Cl ~ Me F
4-OCF3 4-Cl H Me F ~:
4-CF3 4-F H Me F
4-OCF3 4-F H Me F
4-CF3 4-OCF2H H Me F
4-OCF3 4-OCF2H H Me NMe2 4-CF3 4-Br H Me 2 4-CF3 4-C1 4-Cl Me 2 4-C1 4-C1 4-C1 Me NMe2 4-OCF3 4-C1 4-Cl Me NMe2 4-CF3 4-F 4-C1 Me N~t2 4-OCF3 4-F 4-Cl Me 2 4-CF3 4-OCF2H 4-Cl Me piperidino 4-OCF3 4-OCF2H 4-Cl Me morpholino ~.
4-CF3 4-C1 4-CN Me n-Pr 4-OCF3 4-C1 4-CN Me n-Pr 4-CF3 4-F 4-CN Me Sec-Bu 4-OCF3 4-F 4-CN Me 4-Cl-Ph 4-CF3 4-C1 4-CO2Me Me Ph 4-CF3 4-Cl H Et O-~Pr 4-C1 4-Cl H Et O-iPr 4-OCF3 4-Cl H Et O-iPr 4-CF3 4-F H Et O-i~r 4-OCF3 4-F H Et O-lPr :~
4-CF3 4-OCF2H H Et O-iPr :' :- , .. ~ .. , :. . . - .,: " :: . . ... ,, .- i.. :.,.. :, .... .. . .. . ... ..
. : . - , . . : -,, : ,' -- ~:
Z6~ 65 Rl R2 R3 R8 Rg S
4-OCF3 ~-OCF2H H Et O-~Pr 4-CF3 4-Br H Et O-iPr 4-CF3 4-C1 4-Cl Et O-~Pr 4-OCF3 4-C1 4-Cl Et 9-iPr 4-CF3 4-F 4-Cl Et OEt 4-OCF3 4-F 4-Cl Et OEt 4-CF3 4-OCF2H 4-Cl Et OCH2CC13 4-OCF3 4-OCF2H 4-Cl Et 2 4-CF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-OCF3 4-C1 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-F 4-CN Et aPr 4-OCF3 4-F 4-CN Et Ph 3,4-CH2C(Me)2O 4-F 4-CN Et Ph 4-CF3 4-Cl H iPr OEt 4-OCF3 4-Cl B iPr OEt 4-CF3 4-F H iPr OEt .
4-CF3 4-OCF2H H iPr OEt 4-OCF3 4-OCF2H H iPr OEt 4-CF3 4-Br H iPr OEt 4-CF3 4-C1 4-Cl iPr OEt 4-C1 4-C1 4-Cl iPr OEt 4-Br 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt 4-CF3 4-F 4-Cl ~Pr OEt 4-OCF3 4-F 4-Cl iPr OEt 4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2H 4-Cl iPr OEt 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt 4-CF3 4-F 4-CN iPr OEt ~. .
. ' .':' -2~1~Q~65 Rl R2 R3 R8 Rg 4-OCF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt 4-CF3 ~-CN 4-Cl iPr OEt 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt 4-OCF3 4-Me 4-Cl iPr OEt .
4-OCFzH 4-o-~llyl 4-Cl iPr OEt 3,4-CH2C(Me)2O 4-CF3 4-Cl iPr OEt 4-CF3 4-C1 4-CO2Et iPr OEt 4-C1 4-Cl 4-OMe iPr OEt 4-Br 4-C1 4-SCF2CF2H iPr OEt 4-OCF3 4-C1 2 2 iPr OEt 4-OCF2H 4-C1 4-OPh iPr OEt .
3,4-CH2C(Me)2O 4-C1 4-CF3 iPr OEt 4-C~3 4-C1 4-CF3 iPr OEt 4-Br 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-C1 4-No2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu 4-C1 4-Cl H iPr O-n-Bu 4-Br 4-Cl H iPr O-n-Bu 4-OCF3 4-Cl H ~Pr O-D-Bu 4-CF3 4-F H iPr O-D-Bu -4-OCF3 - 4-F H iPr O-n-9u 4-CF3 4-OCF2H N iPr O-n-Bu 4-OCF 4-OCF2H H iPr O-n-Bu 4-CF3 4-Br H iPr O-n-Bu 4-CF3 4-C1 4-Cl iPr O-n-Bu 4-Br 4-C1 4-Cl iPr O-n-Bu 4-OCF3 4-C1 4-Cl iPr O-n-Bu 4-CF3 4-F 4-Cl iPr OCH2CF3 , , - -:
:: ~
2~ 65 Rl R2 R3 RB R9 4-OCF3 4-F 4-Cl iPr 2 3 4-CF3 4-OCF2H . 4-Cl iPr 2 2 4-OCF3 4-OCF2H 4-Cl iPr 2 4-CF3 4-Cl 4-CN iPr 4-OCF3 4-C1 4-CN iPr 2 4-CF3 4-F 4-CN iPr piperidino 4-OCF3 4-F 4-CN iPr Et 4-CF3 4-C1 4-CO2Me iPr Ph 3,4-CH2C(Me)zO 4-C1 4-CO2Me iPr Ph 4-CF3 4-Cl H CH2Ph OEt 4-CF3 4-OCF2H H C~2Ph piperidino ,,~ :
9-CF3 4-Br H CH Ph OCH2CH20Et 4-CF3 4-C1 4-Cl CH2Ph Me ~i ' "
~'' . ~:
.~: .
~, . '~ .
Z~I~Q~L65 ~able 17 Rz ~ J
O ~ N ~ ' S
15~ -~S -R~
R~ O
~, R1 R2 R3 R8 Rg ..
.
4-CF3 4-Cl H MeNMe2 4-OCF3 4-Cl N MeNMe2 4-CF3 4-F H Me 2 4-OCF3 4-F H MeNMe2 4-CF3 4-OCF2H H Me 2 4-OCF3 4-OCF2H H Me 2 4-CF3 4-C1 4-Cl Me 2 ;
4-C1 4-C1 4-Cl MeNMe2 4-Br 4-C1 4-Cl MeNMe2 4-OCF3 4-C1 4-Cl MeNMe2 4-CF3 4-F 4-Cl Me . 2-. , .
.. .. , . . ~ : : . .. . -:
Q~165 Rl a2 R3 R~3 R9 4-OCF3 ~-~ 4-Cl Me NMe2 4-CF3 4-OCF2H 4-Cl Me NMe2 4-OCF3 4-OCF2H 4-~1 Me NMe2 !~
4-CF3 4-Cl 4-CN Me NMe2 4-C1 4-C1 4-CN Me NMe2 4-Br 4-C1 4-CN Me NMe2 4-OCF3 4-Cl 4-CN Me NMe2 4-CF3 4-F 4-CN Me NMe2 4-OCF3 4-F 4-C~ Me 2 4-CF3 4-C1 2 NMe2 4-CF3 4-Cl H Me NEt2 3,4-CH2C(Me)2~ 4-Cl H Me 2 9-CF3 ~-F H Me 2 4-OCF3 ~-F H Me NEt2 4-CF3 ~.4-DCF2H H Me NEt2 4-OCF3 ~-OCF2H H Me NEt2 4-CF3 4-~r H Me N 2 3,4-CH2C(Me)20 4-Ur H Me 2 4-CF3 Ç-~l 4-Cl Me NEt2 4-C1 4-C1 4-Cl Me 2 4-~r 4-C1 4-Cl Me NEt2 4-OCF3 4-C1 4-Cl Me 2 4-CF3 4-'F 4-Cl Me 2 ~
4-OCF3 ~-F 4-Cl Me NEt2 ~ "
4-CF 4-~CF2H 4-Cl Me 2 . ~ f 4-ocr3 4-OCF2H 4-Cl Me NEt2 4-OCF2H ~-~CF2N 4-Cl Me NEt `~
3,4-CH2C(Me)20 4-OCF2H 4-Cl Me 2 4-CF3 4-C1 4_CN Me 2 4-OCF3 4_Cl 4-CN Me 2 "
, : : . . : . . . ...... . . . . - . -: .
: ,, , .: : . :., .: ,. , .. , : . . :
'~: , ' :. . ' :'.:. ~' . ~ .' ... ' ' - ' ' .' ' ' 2C~C~6S
Rl R2 R3 R8 Rg S
4-CF3 4-F 4-CN Me 2 4-OCF3 4-F 4-CN Me NEt2 4-CF3 4-C1 2 NEt2 4-CF3 4-CI H Me piperidino 4-OCF3 4-Cl H Me piperidi~o 4-CF3 4-F H Me Sec-Bu 4-OCF3 4-F ~ Me n-~e~yl 4-CF3 4-OCF2H H Me Ph :
4-OCF3 4-OCF2H H Me Ph 4-CF3 4-Br H Me 4-Cl-Ph 4-C1 4-Pr H Me 4-Cl-Ph 4-CF3 4-C1 4-Cl Me n-Bu 4-C1 4-C1 4-Cl Me n-Bu 4-Br 4-C1 4-Cl Me n-Bu 4-OCF3 4-C1 4-Cl Me n-Bu 4-CF3 4-F 4-Cl Et N 2 .;.-4-OCF3 4-F 4-Cl Et NMÇ2 4-CF3 4-OCF2H 4-Cl Et NEt2 4-OCF3 4-OCF2H 4-Cl Et morpholino 4-CF3 4-C1 4-CN Et iPr 3,4-CH2C(Me)2O 4-C1 4-CN Et D-Bu 4-CF3 4-F 4-CN Et n-Bu . ,-.
4-CF3 4-C1 2 4-MeO-Ph 4-CF3 4-Cl H iPr 2 4-CI 4-Cl N iPr 2 4-Br 4-Cl H iPr ~Me2 4-OCF3 4-Cl H iPr 2 :.
4-CF3 4-F H iPr NMe2 4-OCF3 4-F H iPr e2 ' ..
4-CF3 4-OCF2H H ~Pr NMe2 4-OCF3 4-OCF2H H iPr 2 ' .' ' ' '' ' " .. : " . ' " ' , ' : ': ' ' 2~0Q~65 !`:
Rl R2 ~3 R8 Rg 3,4-CH2C(Me)20 4-oCF2H H iPr NMe2 4-CF3 4-Br ~ iPr NMe2 4-CF3 4-C1 4-Cl iPr 2 4-C1 4-C1 4-Cl iPr NMe2 4-Br 4-C1 4-Cl iPr NMe2 ~-OCF3 4-C1 4-CI iPr 2 4-CF3 4-F 4-Cl iPr NSt2 4-OCF3 4-F 4-Cl iPr NEt2 4-CF3 4-OCF2N 4-Cl iPr 2,6-di-Me-morpholino 4-OCF3 4-OCF2H 4-Cl iPr piperidino 4-CF3 4-C1 4-CN iPr Et 4-OCF3 4-C1 4-CN iPr Et 4-CF3 4-F 4-CN iPr n-Bu 4-OCF3 4-F 4-CN iPr Ph zo ~-Cr3 ~-Cl 4-C02~e Irr ~_CI_rh 25: ~ :
. . . . , : . ,,, . ~ . . . :,.. :: , . : : , 2~ 6~
~able 18 l0Rz ~ R3 0~
l5S ~ -P-Y1Rlo Ra Y R1l Rl R2 R3 R8 yl YlRlo YlRll 4-CF3 4-Cl H tBu S OEt OEt 4-OCF3 4-Cl H tBu S OEt OEt 4-CF3 4-E H tBu S OEt OEt 4-OCF3 4-F H tBu S OEt OEt 4-CF3 4-OCF2H H tBu S OEt OEt 4-OCF3 4-OCF2H H t8u S OEt OEt 4-CF3 4-Br N tBu S OEt OEt 4-CF3 4-Cl 4-Cl tBu S OEt OEt 4-CI 4-Cl 4-Cl tBu S OEt OEt 4-Br 4-Cl 4-Cl tBu S OEt OEt 4-OCF3 4-Cl 4-Cl tBu S OSt OEt 4-CF3 4-F 4-Cl tBu S OEt OEt .
4-OCF3 4-F 4-Cl tBu S OEt OEt 4-CF3 4-OCF2N 4-Cl tBu S OEt OEt 4-Br 4-OCF2H 4-Cl tBu S OEt OEt i ::.
2~ 16S
Rl R2 R3 R8 yl Y1Rlo YlRll 4-OCF3 4-OCF2H 4-Cl tBu S OEt OEt 4-CF3 4-C1 4-CN tBu S OEt OEt 4-OCF3 4-C1 4-CN tBu S OEt OEt 4-CF3 4-F 4-CN tBu S OEt OEt 4-OCF3 4-F 4-CN tBu S OEt OEt 4-CF3 4-C1 4-CO2Me t8u S OEt OEt 4-CF3 4-Cl H tBu S OCH2C(Me)2CH2O
q-OCF3 4-Cl ~ t~u S OCH2C(Me)2CH2O
4-CF3 4-F H tBu S OCH2C(Me)2C~2O
4-C1 4-F H tBu S OCH2C(Me)2CH2O
4-OCF3 4-F H tBu S OCH2C(Me)2CH2O
4-CF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-OCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-CF3 4-CI 4-Cl tBu S OCH2C(Me)2CH2O
4-C1 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-Br 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-Cl tBu S OCH2C(Me)2CH2O
4-CF3 4-F 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 4-F 4-Cl tBu S oCH2C(Me)2CH2O
4-CF3 4-OCF2H 4-Cl tBu S OCH2C(Me)2CH2O
4-OCF3 2 tBu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CN tBu S OCH2C(Me)2CH2O
4-OCF3 4-C1 4-CN tBu S OCH2C(Me)2cH2O
4-CF3 4-F 4-CN tBu S OCH2C~Me)2CH2O
4-OCF3 4-F 4-CN thu S OCH2C(Me)2CH2O
4-CF3 4-C1 4-CO2Me tBu S OCH2C(Me)2CH2O
4-CF3 4-Cl H iPr S OEt OEt 4-C1 4-Cl H iPr S OEt OEt 4-OCF3 4-Cl H ~Pr S OEt OEt 4-CF3 4-F H iPr S OEt OEt 4-OCF3 4-F H iPr S OEt OEt 2~n~6s Rl R2 R3 R~ yl YlRlo YlR
4-OCF2H H iPr S OEt OEt 4-OCF3 4-OCF2H H iPr S OEt OEt 4-CE3 4-Pr H iPr S OEt OEt 4-CF3 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt 10 4-CF3 4-F 4-Cl iPr S OEt OEt 4-OCF3 4-F 4-Cl lPr S OEt OEt 4-CF3 4-OCF2H 4-Cl iPr S OEt OEt 4-OCF3 4-OCF2H 4-CI iPr S OEt OEt 9-CF3 4-C1 4-CN iPr S OEt OEt 15 4-OCF3 4-C1 4-CN iPr S OEt OEt 4-CF3 4-F 4-CN iPr S OEt OEt 4-OCF3 4-F 4-CN iPr S OEt OEt 4-CF3 4-C1 4-CO2Me iPr S OEt OEt 4-CF3 4-Cl H iPr S OCH2C(Me)2CH2O
20 4-OCF3 4-Cl H iPr S OCH2C(Me)2CH2O
4-CF3 4-F H iPr S OCH2C(Me)2CH2O
4-OCF3 4-F H iPr S OCH2C(Me)2CH2O
;
:. .,: ' , - ' : '' ' ' : : :
2~1~Q~65 4-CF3 4-OCF2H H iPr S OCH2C(Me)2CH20 4-CF3 4-Br H lPr S OCH2C(Me)2CH20 4-CF 4-C1 4-Cl iPr S OCH2C(Me)2CH20 4-C1 4:C1 4-Cl ;Pr S OCH2C(Me)2CH20 4-Br 4-C1 4-Cl iPr S OCH2C(Me)2CH20 `G
4-OCF3 4-C1 4-Cl ~Pr S OCH2C(Me)2CH20 4-OCF2H 4-C1 4-Cl lPr S OCH2C(Me)2CH20 4-CF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-9r 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-OCF3 4-F 4-Cl iPr S OCH2C(Me)2CH20 4-CF3 4-OCF2H 4-Cl iPr S OCH2C(Me)2CH20 4-OCF3 2 iPr S OCH2C(Me)2CH20 4-CF3 4-C1 4-CN iPr S OCH2C(Me)2CH20 4-OCF3 4-C1 4-CN iPr S OCH C~Me) CH O
4-CF3 4-F 4-CN iPr S OCN2C(Me)2CH20 4-OCF3 4-F 4-CN iPr S OCH2C(Me)2CH20 4-CF3 4-C1 4-CO2Me iPr S ocH2c(Me) 4-CF3 4-Cl H tBu S OiPr OiPr .
4-CF3 4-F H tBu S OiPr OiPr 4-CF3 4-OCF2H H tBu S OCH2CH2CH20 4-OCF3 4-OCF2H H tBu S OCH2CH2CH20 ...
4-CF3 4-Br H t8u S OCH2CH2CH20 4-CF3 4-C1 4-Cl tBu S OCH2CH20 4-Br 4-C1 4-Cl tBu S OCH2CH20 4-OCF3 4-C1 4-Cl tBu S OCH2CH20 4-CF3 4-F 4-Cl Me S OEt OEt 4-OCF3 4-F 4-Cl ~e S OEt OEt . , 4-CF 4-OCF2H 4-Cl . Me S OEt OEt 4-C1 4-OCF2H 4-Cl Me S OEt OEt 4-CF3 4-F 4-CN tBu O O~t OEt 4-OCF3 4-F 4-CN t~u O OEt OEt 4-CF3 4-C1 4-CO2Me tBu O OCH2C~Me)2CH20 :
- : : ,: . - : : , . :
" . . ~ ;:: .
- : .. :: :: .
lable 19 R2 ~ ~ R3 N ~
O~yl ~
S 11 ~ .
~ -P-Y R,1 R~ Rlo .:
:
Rl R2 R3 R8 yl R1o YlRll R:
4-CF3 4-Cl N iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt 4-CF3 4-F H iPr O Et OEt 4-OCF3 4-F H iPr O Et OEt 4-CF3 4-OCF2~ H iPr O Et OEt 4-OCF 4-OCF H H iPr O Et OEt 4-CF3 4-Br H iPr O Et OEt 4-CF3 4-C1 4-Cl iPr O Et OEt 4-C1 4-C1 4-Cl iPr O Et OEt 4-Br 4-C1 4-C1 iPr O Et OEt 4-OCF3 4-C1 4-Cl iPr O Et OEt 4-OCF2H 4-C1 4-Cl iPr O Et OEt 4-CF3 4-F 4-Cl iPr O Et OEt 4-C1 4-F 4-Cl lPr O Et OEt 4-~r 4-F 4-Cl iPr O Ee OEt L6s 157 :
1 ~2 R3 R8 yl Rlo ylR
i-oCF3 4-F 4-Cl iPr O Et OEt 4-CF3 4-OCF2H 4-Cl iPr O ~t OEt 4-OCF3 4-OCF2H 4-Cl iPr O Et OEt 4-CF3 4-C1 4-CN iPr O Et OEt 4-OCF3 4-C1 4-CN iPr O Et OEt 4-C~3 4-F 4-CN iPr O Et OEt 4-OCF3 4-F 4-CN iPr O Et OEt 4-CF3 4-C1 4-CO2Me iPr O Et OEt 4-CF3 4-Cl H iPr O Et OiPr :. .
4-OCF3 4-Cl H iPr O Et OiPr 4-CF3 4-F H iPr O Et OiPr 4-OCF3 4-F H iPr O Et OiPr ~:
4-CF3 4-OCF2H H iPr O Et OiPr 4-OCF3 4-OCF2H H iPr O Et OPh 4-OCF2H 4-OCF2H H iPr O ~t OPh ::
3,4-CH2C(Me)2O 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh ;
4-CF3 4-C1 4-Cl iPr O Et OPh 4-C1 4-C1 4-Cl iPr O Et OPh :.
4-Br 4-C1 4-Cl lPr O Et OPh 4-OCF3 4-C1 4-Cl iPr O Et OPh 4-OCF2H 4-C1 4-Cl iPr O Et OPh . .
4-CF3 4-F 4-CN tBu O Et OEt 4-OCF3 4-F 4-CN tBu O Et OEt 4-CF3 4-C1 4-CO2Me t8u O Et OEt ~, 9-CF3 4-Cl H tBu O Et OiPr 4-OCF3 4-Cl H tBu O Et OiPr 4-C~3 4-F H tBu O Et OiPr 4-OCF3 4-F H tBu O Et OiPr . .
4-CF3 4-OCF2H H tBu O Et OiPr 4-OCF3 4-OCF2H H Ph O Et OEt :. .. , ~: , .: :. . : , . : , :
:, . . ..
Z~ 6~
R1 R2 R3 R~ yl ~ YlR
i-CF3 4-F H ~Pr S Et OEt 4-OCF3 4-F H iPr S Ph OEt 4-CF3 4-OCF2H 4-Cl tBu S Et OEt 4-OCF3 4-OCF2H 4-Cl tBu S Ph OEt 4-CF3 4-F 4-CN iPr S iPr OiPr 4-OCF3 4-F 4-CN iPr S nPr OEt 4-CF3 4-C1 4-CO2Me tBu S Me OEt ~`
2~Q~L65 159 :
Table ~0 Rz ~ 3 ~ ~ R~
S ~
R9 :, Rl ' R2 R3 Rg 4-CF3 4-Cl H CF3 :
4-CF3 4-F 3 ~;
4-CF3 4-OCF2H 3 ;
4-CF3 4-Br 3 4-C1 4-C14-Cl CF
3~ 4-Br 4-C14-C1 3 3~4-cH2c~Me)2o 4-C1 4-ClCF3 Q~65 160 :~
4-CF 4-F 4,-CN 3 4-CF3 4-Cl q-COzMe CF3 4-CF3 4-C1 M 0-6ecBu 4-CF3 4-F M 0-6ecBu -CF3 4-OCF2H M 0-6ecBu 4-C1 4-OCF2H N 0-6ec8u 4-OCF3 4-OCF2H H 0-6ecBu 4-CF3 4-9r M 0-6ecBu 4-CF3 4-C1 ~I-C1 0-6ecBu 4-C1 4-C1 4-C1 0-6ecBu 4-Br 4-C1 4-C1 O-secBu 4-OCF3 4-C1 4-C1 0-8ecBu 4-CF3 4-F 4-C1 0-6ecBu 4-C1 4-F 4-C1 0-6ecBu 4-OCF3 4-F 4-C1 O-secBu 4-CF3 4-OCF2H 4-C1 0-6ecBu 4-OCF3 4-OCF2H 4-Cl O-~ecBu 4-CF3 4-C1 4-CN 0-6ecBu i~
4-CF3 4-F 4-CN 0-6ecBu ..
4-CF3 4-C1 4-C02Me O-sec8u 4-CF3 4-Cl H O-n-Bu 4-CF3 4-F H O-n-Bu 4-CF3 4-OCF2H H O-n-Bu 4-C1 4-OCF2H H O-n-Bu 4-Br 4-OCF2N H O-n-Bu 4-OCF3 4-OCF2H H O-n-Bu 4-OCF2~ 4-OCF2N H O-n-8u 3~4-cH2c(Me)2o 4-OCF2H H 9-n-Bu 4-CF3 4-Br H O-n-Bu 4-CF3 4-C1 4-Cl O-n-9u 4-C1 4-C1 4-CI O-n-Bu 4-OCF3 4-C1 4-Cl O-n-9u 4-CF3 4-F 4-Cl O-n-hexyl . : ~,-: , ,:: - , : . - ,-. : . : :. ., , - : . . :
. : : . . , , : . ~.:: . .. , . :. , . ::: .: :
- ~ . , : . . , , :~ : . ,: : :. .. ,: .. . . ... .
.. . . .
r~ .
Rl R2 R3 Rg 4-C1 4-F 4-Cl O-n-hexyl 4-OCF3 4-F 4-Cl O-n-hexyl 4-CF3 4-OCF2H 4-Cl O-n-hexyl 4-CF3 4-C1 4-CN. O-n-hexyl 4-CF3 4-F 4-CN O-~-hexyl 4-CF3 4-C1 4-CO2Me O-~-hexyl :
4-CF3 4-OCF2H B CH2ccl3 4-CF3 4-Br H OCH2~C13 :
4-CF3 4-C1 4-Cl OCB2CC13 4-C1 4-C1 4-Cl OCH2CC1 4-OCF3 4-C1 4-Cl OCH2CC13 4-CF3 g-F 4-Cl OCH2CH2OEt 4-CF3 4-OCF2H 4-Cl OCH2CH2OEt 4-CF3 4-C1 4-CN OCH2CH2OEt 4-CF3 4-F 4-CN OCH2CH2OEt q_CF3 4-C1 4-CO2Me OCH2CH2OEt . :~
`~'.
. .
'.' ', '' ',-,': ' ' ," ~ ' .,' '. . -'. ' " `:
' . : ' ' .'., .' . . :. '', . .' , , , .:
6~;
~able 21 R2 ~ R3 }
S -P-1~Rlc ORl, Rl R2 R3 Rlo R
4-CF3 4-Cl H Et Et 3 H Et Et 4-CF3 4-OCF2H H Et Et 4-CF3 4-Br H Et Et 4-CF3 4-C1 4-Cl Et Et 4-Cl . 4-C1 4-Cl Et Et 4-Br 4-C1 4-Cl Et Et 4-OCF3 4-C1 4-Cl Et Et 4-OCF2H 4-C1 4-Cl Et Et 3,4-CH2C(Me)2O 4-C1 4-Cl Et Et 4-CF3 g-F 4-Cl Et St 4-C1 4-F 4-Cl ~t ~t 4-Br 4-F 4-Cl Et Et ,1'.~. ."::
.: - . - . , . ., - , . . .- . .. ; , -.. .. . .. ...... . .. . .... .. .. ...... .. .. . ....
- . ,; , : . , . : . . : .. . . . .
2~ 65 Rl R2 R3 Rlo Rll 4-OCF3 4-F 4-Cl Et Et 4-OCF2H 4-F 4-Cl Et Et 3,4-CH2C(Me)20 4-F 4-Cl Et Et 4-CF3 4-OCF2B 4-Cl Et Et 4-CF3 4-C1 4-CN Et Et 4-CF3 4-F 4-CN Et Et 4-CF3 4-C1 4-CO2Me Et Et 4-CF3 4-9r 2 2 4-CF3 4-C1 4-Cl-CHZcH2-4-C1 4-C1 4-Cl-CH2CH2-4-OCF3 4-C1 4-Cl-CH2CH2-4-C1 4-OCF2H 4-Cl-CH2CH2CH2- .
4-OCF3 4-OCF2H 4-Cl-CH2CH2CH2- ' 4-CF3 .4-F 4-CN-CH2CH2CH2-4-CF3 4-C1 4-CO2Me2 2 2 4-CF3 4-Cl H-CH2C(Me)2CH2-4-CF3 4-F H-cH2cSMe)2~H2-4-CF3 4-OCF2H H-CH2C(Me)2CH2-. ..
4-CF3 4-Br H-CH2C(Me)2CH2-q-CF3 4-C1 4-Cl-CH2C(Me)2CH2-4-C1 4-C1 4-Cl-CH2C(Me)2CH2-4-9r 4-C1 4-Cl-CH2C(Me~2CH2-4-OCF 4-C1 4-Cl-CH2C(Me)2CH2-: - . ~ . . . . ................ .
.
6~;
Rl R2 R3 Rlo Rll 4-OCF2H 4-C1 4-Cl -CH2C(Me)2CH2-3,4-CH2C~Me)2O 4-C1 4-Cl -CH2C~Me32CH2-4-CF3 4-F 4-Cl Ph Ph 4-CF3 4-OCF2H 4-Cl Ph Ph 4-CF3 9-C1 4-CN Ph Ph 4-CF3 4-F 4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph ;.
~ .
~lOQ~65 Table 22 R,~3 ~N ,~R1 "' S
~N--R"
Rl R2' R3 R8 R12 .
4-CF3 4-Cl H nBu nBu 4-C1 4-Cl H ni3u nBu 4-OCF3 4-Cl H nBu nBu 4-CF3 4-F H nBu nBu 4-CF3 4-OCF2H H nBu nBu 4-OCF3 4-OCF2H H nBu nBu 4-CF3 4-Br H nBu nBu ~ .
4-CF3 4-C1 4-Cl nBu nBu 4-C1 4-C1 4-Cl DBu DBu 4-Br 4-C1 4-Cl nBu nBu 4-OCF3 4-C1 4-Cl DBu nBu . .
4-CF3 4-F 4-Cl-CH2CH2CH2CB2CH2-~ !
2C~3Q165 R~ R2 R3 R8 R12 4-CF3 4-C1 4-CO2Me -CH2CH2CH2CH2CH2-4-CF3 4-Cl H -CH2cH2cH2cH2-4-CF3 4-F H -CH2cH2cH2cH2-4-OCF3 4-F H -CH2cH2cH2cH2-4-OCF3 4-OCF2H H -CH2cH2cH2cH2-4-CF3 4-Br H -CH2cH2cH2cH2-4-CF3 4-C1 4-Cl -CH2CH20CH2CH2-4-C1 4-C1 4-Cl -CH2CH20CH2CH~-4-Br 4-C1 4-Cl -CH2CH20CH2CH2-4-OCF3 4-C1 4-Cl -CH2CH20CH2CH2-4-CF3 4-F 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-OCF2H 4-Cl -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CN -CH2CHMeOCHMeCH2- : .
4-CF3 4-F 4-CN -CH2CHMeOCHMeCH2-4-CF3 4-C1 4-CO2Me -CH2CHMeOCHMeCH2_ 4-CF3 4-Cl H Et c 4-CF3 4-F H Et c 4-CF3 4-OCF2H H Et cyclo-c6 4-CF3 4-~r H Et cyClo-c6 4-CF3 4-C1 4-Cl Et Cyclo-c6 4-C1 4-C1 4-Cl Et c 4-Br 4-C1 4-Cl Et c 4-OCF3 4-C1 4-Cl Et c 4-CF3 4-F 4-Cl iPr -CH2CH2CO2E~
4-C1 4-F 4-Cl iPr -CH2CH2CO2ET :
4-CF3 2 iPr -CH2cH2c2ET
i-Cl 2 C iPr -CH2CH2CO2ET
4-Pr 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-OCF 4-OCF2N 4-Cl iPr -CH2CH2CO2ET
., , . .. ~ , . . ,. . , . , . . .: . ., ., . : . .
2C!0Q~6S
Rl R2 R3 R8 R12 4,OCF2H 4-OCF28 4-Cl iPr 2 2 2 3,4-C82C(Me)2O 4-OCF2H 4-Cl iPr -CH2CH2CO2ET
4-CF3 4-C1 4-CN iPr -CH2CH2CO2ET
4-C1 4-C1 4-CN iPr -CH2cH2c2ET
4-OCF 4-C1 4-CN ~F3 2,4-~i-Cl-Ph 4-CF3 4-F 4-CN CF3 2,4-di-Cl-Ph 4-CF3 4-C1 2 3 2,4-di-Cl-Ph -~0 : -.. , , . .. . ., , ~, , . :.
-: ", , . - . ~
;~lOQ16S
~z ~ ~ R3 ~ ~Rl S--SRlo .
Rl R2 R3 R10 :~::
4-CF3 4-Cl H tBu -:
4-OC~ 4-Cl H tBu 4-CF3 4-F H tBu 4-CF3 4-OCF2H H tBu 4-OCF3 4-OCF2H H tBu 4-CF3 4-Br H tBu 4-CF3 4-C1 4-Cl tBu 4-C1 4-C1 4-Cl tBu 4-Br 4-C1 4-Cl tBu 4-OCF3 4-C1 4-Cl tBu :.:-4-OCF2H 4-C1 4-Cl tBu .
4-C~3 4-F 4-Cl tBu ~ s 4-CF3 4-OCF2H 4-Cl tBu ~ .-'.
.. ' !, . ' , . -, . ' , . . ' , ' ' : . : . ': ,. .: , ' : . ', .' :' ' ., .
..' . ''.' ' " , ' ' . ' . " ' " ,. .' . .' ; ' ," ' '., . - .' ' : "." . ', ' ' .' ' ' ' ' :' .'. '.., ,.',', ' . :-" ' . ' ' '~. ' : ' ' ~)Q~65 Rl R2 R3 R~o i-Cl 4-OCF2H 4-Cl tBu 4-OCF3 4-OCF2H 4-Cl tBu 4-CF3 4-C1 4-CN tBu 4-CF3 4-F 4-CN tBu -CF3 4-C1 4-CO2Me tBu 4-CF3 4-Cl H sec-Bu 4-OCF3 4-Cl H 6ec-Bu .
4-CF3 4-F H 6ec-Bu 4-OCF3 4-F H ~ec-Bu 4-CF3 4-OCF2H H 6ec-Bu 4-C1 4-OCF2H H sec-Fu 4-OCF3 4-OCF2H H Ph 4-OCF2H 4-OCF2H H Ph 3,4-CH2C(Me)20 4-OCF2H H Ph 4-CF3 4-Br H Ph 4-CF3 4-C1 4-Cl Ph 4-C1 4-C1 4-Cl Ph 4-Br 4-C1 4-Cl Ph 4-OCF3 4-C1 4-Cl Ph 4-OCF2H 4-C1 4-Cl Ph 3,4-CH2C(Me)20 4-Cl 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ,, .
4-Br 4-F 4-C1 4-Cl-Ph 4-OCF3 4-F 4-C1 4-Cl-Ph 4-OCF2H 4-F 4-C1 4-Cl-Ph 3~4-CN2C(Me)20 4-F 4-C1 4-Cl-Ph 4-CF3 4-OCF2H 4-C1 4-Cl-Ph 4-CF3 4-C1 4-CN 4-Cl-Ph 4-OCF3 4-C1 4-CN 2-Me-4-t-Bu-Ph , . .. - ., ., . . ., , :, . ~: :. .
2~!0Q~6S
Rl R2 R3 Rlo .
4-CF 4-F 4-CN2-Me-4-t-Bu-Ph 4-OCF3 4-F 4-CN2-Me-4 t-Pu-Ph 4-CF3 4-C1 4-CO2Me2-Me-4-t-Bu-Ph 4-CF3 4-C1 ~ 2-NO2-Ph 4-OCF3 4-Cl H 2-NO2-Ph 4-CF3 4-F H 2-NO2-Ph 4-OCF3 4-OCF2H H 2-NO2-Ph 4-CF3 4-Br H 2-NOz-Ph 4-CF3 4-C1 4-C1 2-NO2-Ph 4-C1 4-C1 4-C1 2-NO2-Ph 4 Br 4-C1 4-C1 2-NO2-Ph 4-Cl 9-F 4-C1 2-NO2Ph 4-OCF3 4-F 4-C1 2-NO2Ph 4-CF3 4-OCF2H 4-C1 2-NO2Ph 4-OCF3 4-OCF2H 4-C1 2-NO2Ph . .
4-CF3 4-C1 4-CN 2-NO2Ph 4-OCF3 4-C1 4-CN 2-NO2Ph 9-CF3 4-F 4-CN 2-NO2Ph 4-CF3 4-C1 4-CO2Me2-NO2Ph ~ ' ~
~ ~ :
. .. ~ , . . - , ; i .
~ 0~65 Table 24 0 ~ 3 Ra fi--N
O
Rl R2 R3 Z
4-CF3 4-H 4-Cl CH3 4-CF3 4-H 4-F C~3 4-CF3 4-F 4-Cl CH3 4-CF3 . 4-C1 4-H CH3 ~0 ' 4-C1 4-Cl CN3 4-CF3 4-C1 4-F C~3 4-CF3 4-OCHF2 4-Cl CH3 ...,. :.~ .~ ., ... . . . , : : ,: . : .
: . . , . , : - , . . . : . :
.: .. ... ' . :.. :: . . . : :: - . -2~ 65 Rl R2 R3 z 4-OCF3 4-B 4-Cl ~H3 4-OCF3 4-F 4-Cl CH3 4-OCF3 4-C1 4-Cl CH3 4-C1 4-H 4-Cl CH
4-C1 4-C1 4-Cl CH3 4-C1 4-F 4-Cl CH3 4-Br 4-H 4-H CH3 4-Br 4-H 4-F CN3 4-Br 4-H 4-Cl CH3 4-Br 4-C1 4-H CH3 4-Br 4-C1 4-F CH3 4-Br 4-C1 4-Cl CH3 4-Br q-F 4-H CH3 4-Br 4-F 4-F CH3 4-Br 4-F 4-Cl CH3 4-OCHF2 4-H 4-H ~H3 4-OCHF2 4-H q-Cl Q3 , '. ';'' , ' :'`'.'. '''' ' " ,`''.' '''' ' ' :''' ' , . . . , . . ~. . .`. ~ . . . .
2~ 6S
Rl ~2 R3 Z
4-OCHF2 4-F 4-Cl CH3 4-OCHF2 4-C1 4-Cl C~3 4-CF3 4-~ 4-Cl CH3C~2 4-CF3 4-F 4-Cl CH3CH2 4-CF3 4-Cl g-Cl CH3CH2 4-CF3 4-OCHF2 4-Cl CH3CN2 4-OCF~ 4-H 4-Cl CH3CH2 4-OCF3 4-F 4~H CH3CH2 4-OCF3 4-F 4-Cl CH3CH2 4-OCF3 4-C1 4-Cl CH3CH2 4-C1 4-H 4-Cl N3CH2 6~;
Rl R2 R3 Z
.
4-C1 4-C1 4-Cl CH3CH2 4-C1 4-C1 4-F CH3CH2 :A
4-C1 4-F 4-H CH3CH2 ~
4-C1 4-F 4-Cl CH3CH2 ~ ~
4-C1 4-F 4-F CH3CH2 : .
4-CF3 4-~ 4-Cl C6H5 i.~;
4-CF3 4-H 4-F C6H5 .
lS 4-CF3 4-F 4-H C6H5 4-CF3 4-F 4-Cl C6H5 4-CF3 4-F 4-F C6H5 :
4-CF3 4-C1 4-Cl C6H5 ~ -4-CF3 4-OCHF2 4-Cl C6H5 . :~.
4-OCF3 4-H 4-H C6H5 .
4-OCF3 4-H 4-Cl C6H5 4-OCF3 4-H 4-F C6H5 , . .
4-OCF3 4-F 4-H C6H5 ..
4-OCF3 4-F 4-Cl C6H5 4-OCF3 4-C1 4-H C6H5 ~:
4-OCF3 4-C1 4-Cl C6H5 ':
4-OCF3 4-C1 4-F C6H5 :
4-C1 4-H 4-Cl C6H5 4-C1 4-H 4-F C6H5 : , .' ' - ,:
2~0~65 ., Rl R2 R3 Z
4-C1 4-F 4-Cl C6H5 g-Cl 4-F 4-F C6H5 4-CF3 4-~ 4-Cl CR3~
4-CF3 4-H 4-F C~30 4-CF3 4-F 4-Cl CH30 4-CF3 4-C1 4-Cl C~30 4-CF3 4-OCHF2 4-Cl CH30 4-OCF3 4-H 4-Cl CH30 g-OCF3 4-F 4-H CH30 4-OCF3 4-F 4-Cl CH30 4-OCF3 4-C1 4-Cl CH30 g-Cl 4-N 4-Cl CH30 4-C1 4-C1 4-Cl CH30 ` ' I
~ 2(1~Q~65 Rl R2 R3 Z
4-C1 4-F 4-Cl CH30 .
4-CF3 4-H 4-Cl 4-CF3 4-F 4-Cl H
4-CF3 4-C1 4-Cl H . :
4-CF3 4-OCNF2 4-H H . :
4-CF3 4-OCHF2 4-Cl . H
4-OCF3 4-H 4-Cl H
4-OCF3 4-H 4-F H :
2~ 4-OCF3 4-F 4-Cl H ;
4-OCF3 4-C1 4-Cl H
4-OCF3 4-C1 4-F H .
4-C1 4-H 4-Cl 4-C1 4-C1 4-Cl H
4-Cl 4-C1 4-F H
.. . - .: ; ` . :~: : ,.
, : , ~ . ... : .. ... . .. . .
:, , : . , , . ~ .
2noQ~6s Rl R2 R3 Z
4-C1 4-F 4-Cl H
4-CF3 4-C1 4-Cl BrCH2 4-CF3 4-C1 4-Cl ClCH2 4-CF3 4-C1 4-Cl CF3 4-CF3 4-C1 4-Cl benzyl 4-CF3 4-C1 4-Cl CH3CH2CH2 4-CF3 4-C1 4-Cl CH3(CH2)3 4-CF3 4-C1 4-Cl CH3(CH2)4 4-CF3 4-C1 4-Cl CH3(CH2)5 4-CF3 4-C1 4-Cl CH3(CH2)6 4-CF3 4-C1 4-Cl CH3(CH2)7 4-CF3 4-C1 4-Cl CH3(CH2)9 , 4-CF3 4-C1 4-Cl CH3(CH2)lo 4-CF3 4-C1 4-Cl C13C
9-CF3 4-C1 4-Cl i-P~
4-CF3 4-C1 4-Cl t-Bu 4-CF3 4-C1 4-Cl MeO2C
4-CF3 4-C1 4-Cl EtO2C
4-CF3 4-C1 4-C1 2-Cl-phenyl 4-CF3 4-C1 4-C1 3-Cl-phenyl 4-CF3 4-C1 4-C1 4-Cl-phenyl ~:;
4 CF3 4-C1 4-Cl CH3CH20 4-CF3 4-C1 4-Cl CH3(CH2)20 4-CF3 4-C1 4-Cl CH3~CH2)40 4-CF3 4-C1 4-Cl CH3(CH2)~0 4-CF3 4-C1 4-Cl CH3(CH2)80 4-CF3 4-C1 4-Cl CH3(CH2)100 4-CF3 4-C1 4-Cl phenyl-0 4-CF3 4-C1 4-C1 4-Cl-phenyl-0 .: . : . :" - . :: ' `:: ~ ' : . .: :: , :
2(10(~6S
. , Rl R2 R3 Z
5 . .
4-CF3 4-C1 4-Cl benzyl-O
4-C1 4-C1 4-Cl ClCH2 4 -C1 4 -Cl 4-Cl CF3 4-C1 4-C1 4-Cl benzyl 4-C1 4-C1 4-C1 3(CH2)3 4-C1 4-C1 4-Cl CH32C
4-C1 4-C1 4-Cl CH3CH2O .
- 2 5 ~ ~ :
:, ';
~, ;. . : .. :. :. . . ,.. : . . .
2(1QtQ~65 Table 25 ~ ~ R3 ;
N ~ .
R~ .
O
Nl ~ 9 Rl ~2 R3 R8 Rg , 4-CF3 4-Cl H Me O-nBu 4-OCF3 4-Cl H Me O-~Bu 4-CF3 4-F H Me O-nBu 4-OCF3 4-F H Me O-nBu 4-CF3 4-OCF2H H. Me O-nBu 4-CF3 4-Br H Me O-nBu 4-CF3 4-C1 4-ClMe O-nBu 4-C1 4-C1 4-ClMe O-nBu 4-Br 4-C1 4-Cl.~e O-nBu 4-OCF3 4-C14-Cl Me O-nBu 4-CF3 4-F 4-ClMe O-nBu 4-CF3 4-OCF2H 4-ClMe O-nBu 4-CF3 4-C1 4-CNMe O-nBu ~5 -. . . : . . . . .. : : - . , : : : :
: : : . ,: : : , .: . . . . . : . : . .
, . .. . .. . ,. ,:
0~65 , 180 ~
, . .
Rl R2 R3 R8 Rg ...
,. ~
4-CF 4-F 4-CN Me O-nBu 4-CF3 4-C1 4-C02Me Me O-nBu 4-CF3 4-Cl H Me O-n-he~yl 4-CF3 4-F H Me O-n-he~yl 4-CF3 4-OCF2H B Me O-D_OCtY1 4-CF3 4-Br ~ Me O-n-dccyl 4-CF3 4-C1 4-Cl Me O-n-dodecyl 4-C1 4-C1 4-Cl Me O-n-dodecyl 4-Br 4-C1 4-Cl Me O-n-dodecyl 4-OCF3 4-C1 4-Cl Me O-n-dodecyl 4-CF3 4-F 4-Cl Me 0-6ec-Bu :~
4-C1 4-F 4-Cl Me O-~ec-Bu 4-Br 4-F 4-Cl Me O-sec-Bu 4-OCF3 4-F 4-Cl Me 0-6ec-Bu 4-CF3 4-OCF2H 4-Cl Me 0-6ec-Bu 4-CF3 4-C1 4-CN Me O-iPr :;
4-CF3 4-F 4-CN Me oCH2CH20Et ~.
4-CF3 4-C1 4-C02Me Me OCHz~F3 4-CF3 4-Cl H Me F .:~
4-CF3 4-F H Me 2 4-CF3 4-OCF2H H Me NEt2 4-CF3 4-Br H Me morpholino 4-OCF3 4-Br H Me n-Pr 4-CF3 4-C1 4-Cl Me cec-Bu 4-Br 4-C1 4-Cl Me Ph 4-OCF3 4-C1 4-Cl Me Ph 4-CF3 4 r 4-Cl Et O-iPr -~
4-CF 4-OCF2H 4-Cl Et O-iPr ~;
4-CF3 4-C1 4-CN Et C~2CC13 4-OCF3 4-C1 4-CN Et 2 4-CF3 4-F 4-CN Et 2,6-di-Me-morpholino 4-C1 4-F 4-CN Et 2,6-di-Me-morpholino 4-CF3 4-C1 4-C02Me Et Ph ~~
4-CF3 4-Cl H iPr OEt '~
4-CF3 4-F H iPr OEt ,..:
, . :.' -, , `' ' , ''' ~ ' , ' ' ': ': ~ ' ' . ' ' ' ' ~ ' , ' '. - ' -: ' ' ' ' ' ' ' ' :~ :
~OQ~65 Rl R2 R3 R8 R9 4-CF3 4-OCF2H H iPr OEt 4-C1 4-OCF2H H ~Pr OEt 4-Br 4-OCF2H H iPr OEt 4-OCF3 4-OCF2H H iPr OEt 4-OCF2H 4-OCF2H H iPr OEt 3,4-CH2C(Me)20 4-OCF2H 8 iPr OEt 4-CF3 4-Br H iPr OEt 4-CF3 4-C1 4-Cl iPr OEt 4-OCF3 4-C1 4-Cl iPr OEt 4-CF3 4-F 4-Cl iPr OEt 4-OCF3 4-F 4-Cl iPr OEt 4-CF3 4-OCF2H 4-Cl iPr OEt 4-OCF3 4-OCF2H 4-Cl iPr OEt 4-CF3 4-C1 4-CN iPr OEt 4-OCF3 4-C1 4-CN iPr OEt 4-CF3 4-F 4-CN iPr OEt 4-CF3 4-C1 4-CO2Me iPr OEt 4-OCF3 4-C1 4-CO2Me iPr OEt 4-CF3 4-OMe 4-Cl iPr OEt 4-C1 4-OPh 4-Cl iPr OEt 4-Br 4-SCF2H 4-Cl iPr OEt 4-OCF3 4-No2 4-Cl iPr OEt 4-OCF2H 4-SMe 4-Cl iPr OEt 3,4-CH2C(Me)20 4-SO2Me 4-Cl iPr OEt 4-CF3 4-CN 4-Cl iPr OEt 4-C1 3-C1 4-Cl iPr OEt 4-Br 3-F 4-Cl iPr OEt ~-OCF3 4-Me 4-Cl iPr OEt 4-OCF2H 4-0-allyl 4-Cl iPr OEt 3,4-C~2ClMe)20 4-CF3 4-Cl iPr OEt 4-CF3 4-C1 4-CO2Et ~Pr OEt 4-C1 4-C1 4-OMe iPr OEt 4-Br 4-C1 2 2 t 4-OCF3 4-C1 4-OCF2CF2H iPrOEt .1,~:... ; :
.. . - . . ~....... ,,, . .. : . -.. : .. , :.- .- .. ., , . :.~:. :.
2~Q~6S
Rl R2 R3 Rf~, Rg i-CF3 4-C1 4-CF3 iPr OEt 4-C1 4-C1 4-Me iPr OEt 4-8r 4-C1 3-Cl iPr OEt 4-OCF3 4-C1 3-Br iPr OEt 4-OCF2H 4-Cl g-No2 iPr OEt 4-CF3 4-Cl H iPr O-n-Bu 4-CF3 4-F H iPr O-n-Bu ~ :
4-OCF3 4-F H iPr OCH2CO2Me :
4-CF3 4-OCF2~ H iPr NMe2 4-OCF3 4-OCF2H H iPr piperidino 3,4-CH2C(Me)2O 4-OCF2H H iPr Et :
4-CF3 4-Br H iPr Et 4-OCF3 4-Br N CH2Ph OEt 4-CF3 4-C1 4-CO2Me CH2Ph NME2 .
. . ~ . ~ :
. . .
2~Q~65 Table 26 ' 2 ~ ~ 3 R
O
~ -S -R9 R~ O
R1 R2 R3 R8 Rg 4-CF3 4-Cl H Me 2 4-CF3 4-F H Me 2 4-CF3 4-OCF2H H Me n-hesyl 4-OCF3 q-OCF2N H Me Ph 4-CF3 4-Br H Me 4-Me-Ph :
4-CF3 4-C1 4-Cl Et morpholino 4-C1 4-C1 4-Cl Et iPr 4-Br 4-C1 4-Cl Et n-Bu 4-OCF3 4-C1 4-Cl Et Ph 4-CF3 4-F 4-Cl iPr NMe2 4-CF3 2 iPr piperidino 4-C1 2 iPr Et !':`' ' ':
4-8r 4-OCF2H 4-Cl ~Pr n-Bu 4-OCF3 4-OCF2H 4-C1 iPr Ph 4-OCF~H 4-OCF2H 4-Cl iPr 4-Cl-Ph 2~0Q~6~; ;:
~ble 27 R2 ~ ~ R3 P~
~,~1 .
S`N "
--P--Y Rlo R~ Y Rl 1 ~.
Rl R2 R3 R8 yl YlR 0 YlR
4-CF3 4-Cl H tBu S OEt OEt 4-C1 4-Cl H tBu S OEt OEt 4-Br 4-Cl N tBu S OEt OEt 4-OCF3 4-Cl H tBu S OEt OEt 4-OCF2H 4-Cl H tBu S OEt OEt 3~4-cH2c(Me)2o 4-Cl H t8u S OEt OEt 4-CF3 4-F H tBu S OEt OEt 4-C1 4-F H tBu S OEt OEt 4-Br 4-F H tfiu S OEt OEt 4-OCF 4-F H tBu S OCH2C(Me)2CH20 4-OCF2H 4-F H tBu S OCH2C(Me)2CH20 .
3~4-cH2c(Me)2o 4-F H tBu S OCH2C(Me)2CH20 4-CF3 4-OCF2H H tBu S OCH2C(Me~2CH20 4-C1 4-OCF2H H tBu S OCH2c(Me)2cH20-4-Br 4-OCF2H H t8u S OCH2C(Me)2CH20 ," , .
. .
.,., . ~ ~: : , ti~"' S ~,~
Rl R2 R3 RB yl YlR YlR
S ..
4-OCF3 4-OCF2H H tBu S OCH2C(Me)2CH2O
4-OCF2H 4-OCF2H H tBu S OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-OCF2H H tBu 5 OCH2C(Me)2CH2O
4-CF3 4-Br H tBu S OCH2C(Me)2CH2O
4-C1 4-Br H iPr S OFt OEt 4-Br 4-Br H iPr S OEt OEt 4-OCF3 4-Br H iPr S OEt OEt 4-OCF2H 4-Br H lPr S OEt OEt 3~4-cH2c(Me)2o 4-Br H iPr S OEt OEt 4-CF 4-C1 4-Cl iPr S OEt OEt 4-C1 4-C1 4-Cl iPr S OEt OEt 4-Br 4-C1 4-Cl iPr S OEt OEt 4-OCF3 4-C1 4-Cl iPr S OEt OEt :
4-OCF2H 4-C1 4-Cl iPr S OEt OEt 3,4-CH2C(Me)2O 4-C1 4-Cl iPr S OEt OEt 4-CF3 4-F 4-Cl iPr SOCH2C(Me)2CH2O
4-C1 4-F 4-Cl iPr SOCH2c(Me)2cH2O .
4-Br 4-F 4-Cl iPr SOCH2C(Me)2CH2O .
4-OCF3 4-F 4-Cl iPr SOCH2C(Me)2CH2O
4-OCF2H 4-F 4-Cl iPr SOCH2C(Me)2CH2O
3~4-cH2c(Me)2o 4-F 4-Cl iPr S . OCH2C(Me)2CH2O !;`
4-CF3 2 tBu S OiPr OiPr 4-C1 4-OCF2H 4-Cl tBu S OiPr OiPr 4-Br 4-OCF2N q-Cl t8u S OiPr OiPr 4-OCF3 4-OCF2H 4-Cl t~u S OiPr OiPr 4-OC~2H 4-OCF2H 4-Cl tBu. S OiPr OiPr 2 ~ )2 2 tBu S OiPr OiPr .
4-CF3 4-C1 4-CN tBu S OCH2CH2CH2O
4-C1 4-C1 4-CN tBu S OCH2CH2CN20 4-Br 4-C1 4-CN tBu 2 2 2 :
4-OCF3 4-C1 4-CN tBu S OCH2CH2CH2O
21~0~6S
Rl R2 R3 ~8 yl YlR YlRll 4-OCF2H 4-C1 4-CN tBu S OCH2cN2cH2O ~.
- 3~4-cH2c~Me)2o 4-C1 4-CN tBu S C~2cH2 4-CF3 4-F 4-CN tBu S CH2cH2 4-C1 4-F 4-CN t~u 2 2 4-Br 4-F 4-CN tBu 2 2 4-OCF3 4-F 4-CN Me S OEt OEt 4-OCF2H 4-F 4-CN Me S OEt OEt 3~4-cH2c(Me)2o 4-F 4-C~ Me S OEt OEt 4-Br q-Cl 4-CO2Me tBu O OEt OEt 4-OCF3 4-C1 4-CO2Me tBu O OEt OEt 4-OCF2H 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
3,4-CH2C(Me)2O 4-C1 4-CO2Me tBu O OCH2C(Me)2CH2O
':
.,, . . , . . ;-.. ..
: .,. ::: . . .
- : . :'. ~,, :
- , . .
2(loQl6s ~b~
5, .
l0R2 ~ ~ 3 , ~ .
~"~R1 l5~ -P-YlR
R~ R1O
: ':
R1 R2 R3 R8 yl Rlo Y R
-- !
4-CF3 4-Cl H iPr O Et OEt 4-C1 4-Cl H iPr O Et OEt 4-OCF3 4-Cl H iPr O Et OEt 4-CF3 4-F H iPr O Et O-iPr 4-OCF 4-F H iPr O Et O-iPr .
4-CF3 4-OCF2H H iPr O Et O-iPr 4-OCF3 4-OCF2H H iPr O Et OPh 4-CF3 4-Br H iPr O Et OPh 4-CF 4-Cl 4-Cl iPr O Ph OEt 4-Cl 4-Cl 4-Cl iPr O Ph OEt 4-Br 4-Cl 4-Cl iPr O Ph OEt 4-OC~3 4-Cl 4-Cl iPr O Ph OEt 4-CF3 4-F 4-Cl tBu O Et OEt 4-OCF3 4-F 4-Cl tB~ o Et OEt .
"`' ''. .
OQ~65 Rl R2 R3 RB yl ~10 YlRll .
4-CF3 4-OCF2~ 4-Cl t8u o Et O-iPr 4-OCF3 4-OCF2H 4-Cl t8~ O St O-iPr 4-CF3 4-C1 4-CN Ph O Et OEt q-OCF3 4-C1 4-CN Ph O Et OEt 4-CF3 4-F 4-CN iPr S Ph O-iPr 4-OCF3 4-F 4-CN tBu S Et OEt ;: :
:~!
OQ~6S
189 ::
Table 29 R2 ~ /~3 - !
N~
~ ~ R~
S`GP
R~ :
Rl ~ R2 R3 Rg 4-OCF3 4-F H O-cec-Bu 4-CF3 4-OCF2~ H 0-6ec-Bu . : .
4-Br 4-OCF2H H 0-6ec-9u 4-OCF3 4-OCF2H H 0-6ec-Bu 4-CF3 4-Br H O-n-Bu 4-CF3 4-C1 4-Cl O-D-Bu 4-C1 4-C1 4-Cl O-n-Bu 4-Br 4-C1 4-Cl O-n-Bu 4-OCF3 4-C1 4-Cl O-n-Bu i , ~, 4-CF3 4-F 4-Cl O-n-hexyl ,~
4-CF3 4-OCF2H 4-Cl O-D-hexyl ~-4-OCF3 4-OCF2H 4-Cl O-n-h~xyl ,.
: - , : - . . .,:. . , . - : . : : . : . - : . :, . . . - - j QQ~6S
Rl R2 R3 Rg .
4-OCF3 4-C1 4-CN ~CH2CC13 4-CF3 f.-F 4-CN OCH2CC13 4-CF3 4-C1 4-CO2Me 2 2 ~;, , -., , . .. . ... , ,, . :
. '. ` : .. ' : ': .: : . ' : : . . ::: .. :: . : , : . : . . ' ' ~l :
Z~OQ~65 ~le 30 ~ ~ R
I O
S
OR
Rl ~2 R3 R10 R~
4-CF3 4-Cl H Et Et 4-CF3 4-F H Et Et `~
4-CF3 4-OCF2H H Et Et ~ :~
4-CF3 4-Br H -CH2CH2- ~
4-CF3 4-C1 4-Cl -CH2CH2- ;.
4-Cl 4-Cl 4-Cl 2 2 4-OCF3 4-Cl 4-Cl -CH2CH2-4-CF3 4-F 4-Cl -CH2C~2CH2-4-OCF3 4-F 4-Cl 2 2 2 .
4-CF3 4-OCF2H 4-Cl -CH2CH2CH2-4-OCF3 4-OCF2H 4-CI ,, ' .' '', :~".', .' '.
. , . , . ' ' .: . ~ :.. :. , '' . .; ,~ ' ~, :, ;' .
2(:~0Q~L65 Rl R2 %3 ~10 ~11 4.CF3 4-Cl 4-CN 2 ~ )2 2 4-C~CF3 4-C1 4-CN -CH2C(Me)2CH2-4-CF3 4-F 4-CN Ph Ph 4-CF3 4-C1 4-CO2Me Ph Ph .: , . . ~ ~ ~ . , : ,: . . :, : :
: :, . . . , : .
- : . . : ::
2(,~65 193 .
Table 31 R2 ~ ~ 3 N ~
~ t Rl R2 R3 R8 R12 :. .
4-C~ 4-Cl H nBu nBu :
4-CF3 4-F H nBu nBu 4-CF3 4-OCF2H H nBu nBu 4-CF3 4-Br 2 2 2 2 2 4-CF3 4-C1 4-Cl -CH2CH20CH2CH2-4-C1 4-C1 4-Cl -CH2CH20CH2CH2-4-OCF3 4-C1 4-Cl -CH2cH2cH2cH2- ::
4-CF 4-F 4-Cl -CH2CH~Me)OCH(Me)CH - , .
4-OCF3 4-F 4-Cl -CH2CH(Me)OCH(Me)CH - ,' 4-CF3 2 Et c 4-OCF3 4-OCF2H 4-Cl Et cycl-C6Hll ' 4-CF3 4-C1 4-CN Et cyclo C6Hll , 4-CF3 4-F 4-~N lPr -CH2cH2c2Et 4-CF3 4-C1 4-CO2Me CF3 2,4-~i-Cl-Ph .: ,., ." ., . ,. , ,, ; , : ,. . ,. :: :, , . ~ . . : . ~, . , 2~0Q~65 ~ble 32 5 . .
1~ ~ N ~ R3 ~,,~R
S
~ R~
Rl R2 R3 R10 4-CF3 4-Cl H tBu 4-CF3 4-F H tBu 4-CF3 4-OCF2H H sec-Bu 4-OCF3 4-OCF2H H sec-Bu 4-CF3 4-Br H 6ec-Bu 4-CF3 4-C1 4-Cl Ph 4-C1 4-C~ 4-Cl Ph 4-OCF3 4-C1 4-Cl Ph 4-CF3 4-F 4-C1 4-Cl-Ph 4-C1 4-F 4-C1 4-Cl-Ph ;
4-OCF3 4-F 4-C1 4-Cl-Ph 4-CF3 4-OCF2H 4-C1 4~Cl-Ph 4-OCF3 4-OCF2H 4-C1 2-Me-4-t-Bu-Ph 2~ 6S
Rl R2 R3 Rlo , .
i--CF3 4-C1 4-CN 2-Me-4-t-Fu-Ph 4-CF3 4-F 4-CN 2-NO2-Ph 4-CF3 4-C1 4-CO2Me 2-NO2-Ph '.':' '.
. ~'~
3C . , .
:', .
3S ::
2(10Q~6S
Formulation and Use The compounds of this invention will generally be used in formulation with a carrier comprising a liguid or solid diluent or an organic solvent.
Useful formulations of the compounds of this invention are prepared in conventional ways. They include dusts, baits, traps, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of thes can be applied directly.
Sprayable formulations can be e2tended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99% solid or liquid diluent(s).
More specifically, they will contain these 20 ingredients in the following approximate proportions: -Percent by Weipht Active Inaredient Diluent(s~ Surfactant(s) 25 Wettable Pawders 25-90 0-74 0-10 Oil Suspensions, 1-50 40-95 0-35 Emulsions, Solutions (including Emulsifi-able Concentrates) Dusts 1-25 70-99 0-5 Granules, Baits 0.01-95 5-99 0-15 and Pellets High Strength 90-99 0-10 0-2 Compositions 35Lower or higher levels of active ingredient can, of course, be present depending on the intended : . - . . . . - . . .:
. ~ .: , ~ .:
-... .- . ...
- - - - . : . .
, - , : - ,: , : : . .
- - : :
- : . : . :. . : .
2~Q~6~
use and the physical pr~perties of the compound.
Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mi~ing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers, n 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, ~Solvents Guide,~ 2nd Ed., Interscience, New York, 1950. Solubility under 0.1%
is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at O~C. ~McCurcheon~s Detergents and .' Emulsifiers Annual,~ Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, ~Encyclopedia 20 of Surface Active Agents," Chemical Publ. Co., Inc., '~
New York, 1964, list ~urfactants and recommended uses.
All formulations can contain minor amounts of addi-tives to reduce foam, caking, corrosion, microbiologi-cal growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.
The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, griding as in a hammer or fluid energy mill. Suspensions are prepared by wet-milling (see, for e~ample, U.S. 3,060,0~4). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by a~glomeration techniques. See Browning, "Agglomeration,~ Chemical -.. : . ,. .. : .
:. ~ : ... .. :
Engineerina, December 4, 1967, pages 147 and follow-ing, and ~Perry's Chemical Engineer's Handbook," 4th Ea., McGraw-Hill, New York, 1963, pages 8 to 59 and following.
Many of the compounds of the invention are most efficacious when applied in the form of an emul-sifiable concentrate mixed with a spray oil or spray oil concentrate. Although any oil can be used as a spray oil, spray oils usually have these character-istics: they are not phytoto~ic to the crop sprayed, and they have appropriate viscosity. Petroleum based oils are commonly used for spraying. In some areas, crop oils are preferred such as the following:
Common Crop Oils Used as Spray Oils Corn Oil Linseed Oil Cottonseed Oil Soybean Oil Coconut Oil Sunflower Oil Rapeseed Oil Olive Oil Peanut Oil Palm Oil Safflower Oil Sesame Oil Mustardseed Oil Castor Oil The following oils also meet the criteria for a spray oil: mineral, fish and cod liver oil.
Spray oil concentrates comprise a spray oil together with one or more additional ingredients such as emulsifiers and wetting agents. A number of useful spray oil and spray oil concentrates can be found in "A Guide to Agricultural Spray Adjuvants Used in the United States~ by Thomson, Thomson Publications, California, 1986.
Examples of useful arthropodicidal formulations of compounds of the present invention sre as follows.
:. , - . . :
-. ~ : . . , - ........... -. . : : . - ::
.. . .
Example A
Em~lsifiable Concentrate methyl 4-[3-(4-chlorophenyl)-1-[r(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]- , amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
20%
blend of oil soluble sulfonates and polyo~yethylene ethers 10%
isophorone 70%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filtex is included in packaging operation to insure the substantial absence of e~traneous undissolved material in the product.
Example B
Wettable Powder methyl 4-t3-(4-chloroPhenYl)-l-t[(etho~YcarbonYl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl~benzoate.
30%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 63%
The active ingredient is mixed with the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 5-mesh ~creen.
E~amDle C
Pust methyl 4-t3-(4-chlorophenyl)-1-[[(ethosycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl3-4,5-di-hydro-lH-pyrazol-4-yl3benzoate.
, - - . - . , ., ., , . . . : :
.
,, , .. : . .
s Wettable powder of Example B 10%
pyrophyllite (powder) 90%
s The wettable powder and the pyrophyllite diluent are thoroughly blended and then packeged.
The product is suitable for use as a dust.
Example D
Granule methyl 4-[3-(4-chlorophenyl)-1-t[(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoro-methyl)phenyl]amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate. 10%
attapulgite granules (low volative matter, 0.71/9/30 mm; U.S.S. No.
25-50 sieves) 90~
The active ingredient is dissolved in a vola-tile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven o~ by heating.
The granules are then allowed to cool and are packaged.
Example E
Emulsifiable Concentrate methyl 9-t3-~4-chlorophenyl)~ (ethoxycarbonyl)(l-methylethyl)amino]thio]-N-t9-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
10%
blend of oil soluble sulfonates and polyoxyethylene ethers 4%
isophorone 86%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in packaging operation to insure the ab-sence of any extraneous undissolved material in the product.
' , .
' . . .: - , . , . ., . .. ; . - . ~ . ' ' . ,. ' ' , ~ ,: , : : ,' .:
' . " :'' : . , :: ~ ' ' : , , , .:.-': ,. . ::. ,, ' : ',' ' : , ' , :-; ' .
,,', . -: : ' ~ ~ . .: . . ' , ' . '. .' :'. . ' ' . ~ -: , ' - ' ' .. . ' ; ' . : : . , -: ,' : :., .,. .' ,. -:: ' ' ' . : :
2C!QQ~L65 Example F
Wettable Powder methyl 4-[3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]-amino]carbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
80%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 3%
The active ingredient is blended with the inert materials in a blender. After grinding in a hammermill, the material is reblended an sifted through a U.S.S. 50-mesh screen and packaged.
Example G
Dust wettable powder of E~ample F5%
pyrophyllite (powder) 95%
The wettable powder and the pyrophyllite diluent are thoroughly blended and then packaged.
The product is suitable for use as a dust.
E~am~le H
Granule methyl 4-[3-(4-chlorophenyl)-1-[[(etho~ycarbonyl)(l-methylethyl)amino]thio~-N-[4-(trifluoromethyl)phenyl~-- 30 amino]carbonyll-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
10%
attapulgite granules (low volative matter, 0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90~
The active ingredient is dissolved in a suit-able solvent and sprayed onto dedusted attapulgite granules in a double cone blender. The granules are warmed to drive off solvent, cooled and packaged.
~ , .
,. . : , . . . :: - . .
. , ~ . -, 2~ 6S
~02 Example I
Granule wettable powder of Ex~mple F 15%
gypsum 69~
potassium sulfate 16%
The ingredients are blended in a rotating mixer and water is sprayed on to accomplish granu-lation. When most of the material has reached the desired range of 0.1 to 0.42 mm (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These 15 granules contain 12% active ingredient. ;
Example J
Solution methyl 4-[3-(4-chlorophenyl)-1-[t(ethoxycarbonyl)(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)phenyl]
amino]carbonyI]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
1~%
4-butyrolactone B5%
The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
ExamDle K
Oil Suspension methyl 4-t3-(4-chloroPhenYl)-l-ll(etho~YcarbonYl)(l-methylethyl)amino]thio]-N-t4-(trifluoromethyl)phenyl]- .. .
aminolcarbonyl]-4,5-di-hydro-lH-pyrazol-4-yl]benzoate.
20~
sodium alkylnaphthalenesulfonate 4%
sodium ligninsulfonate 4%
low viscosity methyl cellulose 3%
attapulgite 69%
!''1`` ':
" . , ~, , , . . , , , , . . ,, , , :, , ,, , . ,, . ~, , ,~, ...
,: , . : .,. , ~ . ~ , . . . :
:
The active ingredient is blended with the -inert materials in a blender. After grinding in a hammermill to produce particles substantially all below 100 microns, the material is reblended and sifted through a U.S.S. 50-mesh screen and packaged.
Example L
Aaueous Suspension methyl 4-t3-(4-chlorophenyl)-1-[[(ethoxycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 40%
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ether 0.5%
disodium phosphate 1.0%
monosodium phosphate 0.5%
polyvinyl alcohol 1.0%
water 56.7 The ingredients are blended and ground together in a sand mill to produce particles substantially all under 5 microns in size.
E~ample M
Pil Suspension methyl 4-t3-(4-chlorophenyl)-1-[t(etho~ycarbonyl)-(l-methylethyl)amino]thio]-N-[4-(trifluoromethyl)-phenyllamino]carbonyl~-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 35-0%
blend of polyalcohol carbo~ylic 6.0%
esters and oil soluble petroleum sulfonates ~ylene range solvent 59.0%
- , .
: .
. . .
: .. . . .
:. ~ , .. - .: . .. . - ; ~ . -. .
2~ 65 The ingredients are combined and ground tegether in a sand mill to produce particles substantially all below 5 microns. The product can be used directly, e~tended with oils, or emulsified in water.
Example N
Emulsifiable Concent~ate methyl 7-chloro-2-[[N-[[[(he~ylo~y)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 5%
blend of oil soluble sulfonates and polyoxyethylene ethers 4%
~ylene 91~
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen 20 filter is included in packaging operation to insure ~
the absence of any extraneous undissolved material in ;
the product.
Example O
Wettable Powder methyl 7-chloro-2-[[N-[[[(he~yloxy)carbonyl3-methyl-amino]-thio]-N-14-(trifluoromethyl)-phenyl]amino]-carbonyl]-3,3a~4,5-tetrahydro-2H-benz[g]indazole-3a-carbo~ylate. 30%
sodium alkylnaphthalenesulfonate 2% !~-sodium ligninsulfonate 2%
synthetic amorphous silica3%
~aolinite 63%
.' .. , :, . : . . . ~ ,. . ~ ,,. .. , ... . . :
. - ~ .. . .- , . - .:
,, . ~ ,, - : : , ,.. , : ..
. . - -: ~ 0 ~, The active ingredient, warmed to reduce viscosity, is sprayed onto the inert materials in a blender. After grinding in a hammer-mill, the material is reblended and sifted through a 50 mesh screen.
E~amPle P
Solution methyl 7-chloro-2-[[N-[[[(hexyloxy)carbonyl]-methyl-amino]-thio]-N-[4-(trifluoromethyl)-phenyl]amino~-carbonyl]-3,3a,4,5-tetrahydro-2H-benz[g]indazole-3a-carboxylate. 10%
isophorone 90%The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.
E~mPl~ Q
Bait Granules methyl 4-[3-(4-chlorophenyl)-1-[l(ethoxycarbonyl)- -(l-methylethyl)amino]thio]-N-[4~(trifluoromethyl)-phenyl]amino]carbonyl]-4,5-dihydro-lH-pyrazol-4-yl]benzoate. 3.0%
blend of polyetho~ylated nonyl- 9.0%
phenols an sodium dodecylbenzene benzene sulfonates ground up corn cobs 88.0%
The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I, II and/or III can also be mised with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of effective pesticide protection.
Examples of other agricultural protectants with which compounds of the present invention can be mised or formulated are as follows.
Ins~icides:
3-hydro~y-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran) 0-[2,4,5-trichloro-a-(chloromethyl)benzyl]ophosphoric acid, 0',0'-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion) phosphorothioic acid, 0,0-dimethyl, 0-~-nitrophenyl ester (methyl parathion) methylcarbamic acid, ester with a-naphthol (carbaryl) methyl 0-(methylcarbamoyl)thiolacetohydro~amate (methomyl) N~-(4-chloro-Q-tolyl)-N,N-dimethylformamidine (chlordimeform) 0,0-diethyl-0-(2-isopropyl-4-methyl-6-pyrimidylphos-phorothioate (diazinon) -octachlorocamphene ~tosaphene) 30 0-ethyl 0-p-nitrophenyl phenylphosphonothioate (EPN) :-(S)-a-cyano-m-phenosybenzyl(lR,3R)-3-(2,2-dibromovinyl) -2,2-dimethylcyclopropanecarbosylate (deltamethrin) Methyl N',N'-dimethyl-N-[(methylcarbamoyl)osy]-l-thioosamimi-date (osamyl) cyano(3-phenosyphenyl)-methyl-4-chloro-a-(1-methyl-ehtyl)benzeneacetate (fenvalerate) .
, - - . ~ : - , ~ ,, - . , , , ~ ~
- ,, ~ . ., .. ~, : :
~Q~6!S
(3-pheno~yphenyl)methyl(~)-c s,~L~n~-3-(2,2-dichloro ethenyl)-2,2-dimethylcyclopropanecarboxylate (perme-thrin) a-cyano-3-pheno~ybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carbo~ylate (cypermethrin) O-ethyl-S-(D-chlorophenyl)ethylphosphonodithioate ', (profenofos) phosphorothiolothionic acid, 0-ethyl-0-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos).
Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzureon, methoprene, buprofezin, thiodicarb, acephate, azinphos-methyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathio, methamidiphos, monocrotphos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, metal-dehyde and rotenone.
.
Fun~icides:
methyl 2-benzimidazolecarbamate (carbendazim) :
tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) - 30 manganese ethylenebisdithiocarbamate ~maneb) 1,4-dichloro-2,5-dimethosybenzene (chloroneb) methyl l-(butylcarbamoly)-2-benzimidazolecarbamate (benomyl) ;, , : . ,: . .
: ~ , , . :
- - - , , :
2 ~ 65 1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dio~olan-2-ylmethyl]-lH-1,2,4-triazole (propiconazole) 2-cyano-N-ethylcarbamoy-2-methoxyiminoacetamide (cymoxanil?
1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-2-butanone (triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) 10 N-(trichloromethylthio)phthalimide (folpet) ~-:
l-[[tbis(4-fluorophenyl)]tmethyl]silyl]methyl]-1H-1,2,4-triazole.
~Ç1~118i ~
S-methyl l-(dimethylcarbamoyl)-N- (methylcarbamoyloxy)-thioformimidate S-methyl l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate ~.
N-isopropylphosphoramidic acid, 0-ethyl 0'-[4-(methylthio)-m-tolyl]diester (fenamiphos) ~ac~ericides:
tribasic copper sulfate streptomycin sulfate :
Acaricides:
senecioic acid, ester with 2-~Q~-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-cithiolo[4,5-B]quinoxalin-2-one 30 (oxythioquinox) -:
ethyl 4,4'-dichlorobenzilate (chlorobenzilate) 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethanol .
(dicofol) bis(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohe~yltin hydroxide (cyhexatin) trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo-thiazolidine-3-carboxamide (hexythiazox) -. . , . . . . . .- . ,.: , ~ . , .: ., - -. : ... ,. -.:: . - . . .... . .. . . . .. : . :.. . : . : . . .
s amitraz propargite 5. fenbutatin-o~ide .
~ioloical Bacillus thuringiensis Avermectin B.
Utility The compounds of the present invention ex-hibit activity against a wide spectrum of foliar and soil-inhabiting, livestock, household and public health arthropods. Those skilled in the art will recognize that not all compounds will be equally effective against all arthropods but the compounds of this invention display activity against economical- ~:
ly important pest species, such as grasshoppers and cockroaches including Berman or American roaches;
thrips; hemipterans: plant bugs (Miridae) such as tarnished plant bugs, lace bugs (Tingidae), seed bugs (Lygaeidae) such as cinch bugs, stink bugs (Pentatomidae), leaf-footed bugs (Coreidae) such as 25 squash bug, and red bugs and stainers (Pyrrocoridae) ::
such as cotton stainer; also homopterans such as whiteflies, aphids such as the green peach aphid, greenbug and cotton aphid, leafhoppers, spittlebugs and planthoppers such as aster leafhopper, potato leafhopper and rice planthoppers, psyllids such as pear psylla, scales (coccids and diaspidids) and mealybugs; coleopterans including weevils such as boll weevil and rice water weevil, grain borers, chrysomellid beetles such as Colorado po~ato beetle, flea beetles and other leaf beetles, coccinellid beetles such as Me~ican bean beetle.
. . - .: . - - . . ,. . .. . , . . . . : .. ~ , ~ ::. . -- .. .. ~ . .. : . .. - . . .. . . . - ... . . :
. . . . . . . . ~ .. . . .
.. .. . . . . , ., : . . - .
: . . . .
Activity is also shown against soil insects such as southern corn rootworm and wireworm;
lepidopterous larvae including noctuids such as fall armyworm, beet armyworm, other Spodoptera spp., .
Heliothis spp. such as virescens, Heliothis zea, cabbage looper, green cloverworm, velvetbean caterpillar, cotton leafworm, black cut- worm, and other noctuid cutworms and including pyralids such as European corn borer, navel orange- worm, and stalk/stem borers and including tortricids like codling moth and grape berry moth as well as other lepidopterous larvae such as pink bollworm and diamodback moth; and dipterans such as leaf-miner, soil maggots, midges, and tephritid fruit flies; house fly, Musca domestica; stable fly, Stomoxys calcitrans; black blow fly, Phormia reaina;
face fly, Musca autumnalis; black fly, Simulum meridionale; yellow fever mosquito, Aedes eaVPti;
German cockroach, Blattella aermanica; carpenter ants, Camponotus pennsylvanicus and eastern subterranean termite, ReticuLitermes flavipes. The pest control afforded by the compounds of the present invention is not limited, however, to these species.
The specific species, for which control is ~
esemplified below, are: fall armyworm, Spodoptera ~ .
frugiperda; tobacco budworm, Heliothis virescens; ~!
southern corn rootworm, Diabrotica undecimpunctata 30 howardi; aster leafhopper, Macrosteles fascifrons. `
The pest control afforded by the compounds of the present invention is not limited, however, to these species. ~
3~ Application -.
Arthropods are controlled in agricultural crops and animals and humans are protected by applying one or more of the compounds of this invention, in an ''."' ' . ., . . .- , . . . ...
.
~q31Q~6~
effective amount, to the locus of infestation, to the area to be protected, directly to the pests to be controlled, or to their environment. A preferred method of application is by spraying with spray equipment that distributes the compound on the foliage, in the soil, or to the plant part that is infested or needs to be protected. Alternatively, granular formulations of these compounds can be applied to soil or foliage or, optionally, incorporated into the soil. Either aerial or ground application can be used. Because of the diversity of behavior patterns and habitats of the animal and human health species, many different methods of application are employed. These include direct and residual sprays, baits, ear tags, soil treatment and many others.
The pyrazoline compound(s) of this invention can be applied directly, but most often application will be of a formulation comprising one or more com-pounds of this invention, in an agriculturally suit-able carrier or diluent. A most preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. The compound(s) can also be incorporated into baits which are consumed or in devices such as traps and the like that entice the arthropod to ingest or otherwise contact the tosicant compound(s).
The rate of application of Formula I, II or III compounds required for effective control will depend on such factors as the æpecies of arthropod to be controlled, the pest's life stage, its size, its location, the host crop, time of year of application, ambient moisture, temperature conditions, and the like. In general, application rates of 0.01 to 2 kg of active ingredient per hectare are sufficient ,: .. :: . . -. - - . ,. ; ................ ,, - ~ .,.. . -, - . - ., - :, . : . . ........................... . . .
, ,: .. ~ ., : , . . ................. .
,, , ~ :: ~ ., -. . . , s to provide effective control in large scale field operations under normal circumstances, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required for agricultural use, or 0.1 mg/ft2 to 20 mg/ft2 for home use, depending upon the factors listed above.
The following Examples demonstrate the con-trol efficacy of compounds of Formulae I, II and III
on specific arthropod pests wherein Compounds 1 through 55 are depicted in the E~amples and Tables A, B and C and summarized in Table D, respectively.
-)s Table D
R2 ~ O2CH3 N-N ~ ' O S Y
CMPD Rl R2 Y
1 CF3 H N(CH[CH3]2)CO2Et 2 CF3 H CO2~-BU
3 CF3 H N(n-Bu)2 4 CF3 5-Cl N(cH3)co2n-he CF3 H N(CH3)CO2n-BU
6 CF3 H N(CH3)co2Et 7 CF3 4-F N(CH3)CO2n-BU
8 CF3 H N(cH3)co2cyclohe~yl :
9 CF3 H ~ N(CH3)CO2n-octyl :
3~ CF3 H N(c~3)co2n-decyl 11 CF3 4-F N[CH(CH3)2]cO2Et : -12 CF3 H N(cH3)co2n-dode 13 CF3 H N(CH3)C
14 CF3 5-Cl CO2~-BU
CF3 5-Cl NlCH(CH3)2]Co2Et .
16 CF3 5-Cl N(CH3)CO2Et , .-, ~: . ., . , - . . ~ ; .. .. :
.. : - . ~: .. , . ~ , , , , . :, . , , :
.: , ....... ...~ . : , . ::
- ~ . .. : . . . ~ . .. : :: : , , . :
2noQ~6s CMPD Rl R2 Y
17 CF3 S-Cl N(cH3) 18 CF3 4-F CO29-Bu 19 CF3 5-Cl N(CH3) C02n-BU
CF3 5-Cl N[CH3(CH3) 2 ] C02n-Bu 1021 CF3 5-Cl N(cH3)co2n-dodecyl ~ .
22 CF3 5-Cl NtcH3)co2cyclohe~
23 CF3 5-Cl N(CH3)CO2(CH2)2OB
24 CF3 5 Cl N(CH3)cO2cl4H29 CF3 5-Cl N(CH3)cO2cl6H33 1526 CF3 5-Cl N(CH3)cO2cl8H37 27 CF3 5-Cl N(CH3)cO2c22H45 28 CF3 5-Cl N(CH3)Co2(cH2)2o(cH2)2oBu `
h ~ ~ Rl ' O SY .~:.
~ ... .
,:
: ':
. .
~:
', -.
.. . . : .: ~- , ' :.. , : . .. . . ~
2CIO~L6~;
5 CMPD Rl R2 R3 Y
29 CF3 4-C1 4-F N[cH(cH3)2]co2Et 31 CF3 4-C1 4-F N~cH(cH3)2]co2Bu 32 ~F3 4-C1 4-F N[CH(CH3)CH2CH3]CO2Et 33 CF3 4-C1 4-F CO2s-Bu 34 CF3 4-C1 4-F N(CH3)CO2cyclohe~yl 1 5 j~R~, R2 /~ .
N~N/
O~ ~, ~ R
CMP~ Rl R2 R3 Q
CF3 4-C1 4-Cl SN[cH(cH3)2]co2Et CF3 4-C1 4-Cl SN(cH3)co2~-Bu 30 36 CF3 4-C1 4-Cl SCO2s-Bu 37 Cl 4-C1 4-Cl SCO2s-Bu : . .
38 CF3 4-C1 4-Cl CO2CH3 CF3 4-C1 4-Cl SN[CH~CH3)2]cO2Et 35 41 CF3 4-C1 4-Cl COCH3 43 Br 4-C1 4-F COCH3 :
. . .
.
~ :
2C10Q~6S
~"
CMPD Rl R2 R3 Q
CF3 4-C1 4-F COPh 4 6 CF3 4-C1 4-Cl COCH2CH3 10 47 CF3 4-C1 4-Cl COCOCH2CH3 48 CF3 4-C1 4-Cl COn-Bu .
49 Cl 4-C1 4-Cl COCH3 Cl 4-C1 4-Cl COCH2CH3 ; .
51 Cl 4-C1 4-Cl C2CH3 15 52 CF3 4-C1 4-Cl CO-4-Cl-Ph 5 3 CF3 4 -C 1 4 -C 1 COt -Bu 54 CF3 4-C1 4-Cl CO2Ph , ~i . ::. .:, - . . :. . .
::
:,- : , , i . , . :
- \
2(10Q~L65 E~
Fall Armyworm Test units, each consisting of an 8-ounce plastic cup containing a layer of wheat germ diet, approx. 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (Spodoptera frugiperda~ were placed into each cup. Solutions of each of the test compounds (acetone/distilled water 75/25 solvent) were sprayed onto the cupsj a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which 15 discharged the spray at a rate of 0.5 pounds of :
active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. The cups were then covered and held at 27C
and 50% relative humidity for 72 hours, after which time mortality readings were taken.
Of the compounds tested on fall armyworm, the following resulted in greater than or equal to 80%
mortality: 1, 2, 9, 5, 6, 7, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41,-42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, and 54.
Example 57 Tobacco Budworm The test procedure of E~ample 56 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) except that mortality was assessed at 98 hours. Of the compounds tested on tobacco budworm, the fiollowing resulted in greater than or equal to 80% mortality: 2, 4, 7, 11, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41, 42, 43, 44, 45, 46, `
48, 49, 50, 51, 52, 53 and 54.
- . ~ ,, , , . , : ................. . . . , - ., . , . . -:, : : . : .
Z~Q~L65 ~alnple ~
European Corn Borer Test units, each ~onsisting of an 8-ounce plastic cup containing a one-inch square of wheat germ~soyflour diet, were prepared. Five third-instar larvae of the European corn borer (Ostrinia nubilalis) were placed into each cup. Sets of three test units were sprayed as described in E~ample 56 with indi-vidual solutions of the test compounds. The cups were then covered and held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested on European corn borer, the following resulted in greater than or equal to 80% mortality: no testing.
E~ample 59 Southern Co~n Rootworm Test units, each consisting of an 8-ounce plastic containing 1 sprouted corn (Zea mays) see, were prepared. Sets of three test units were sprayed as described in E~ample 56 with individual solutions of the test compounds. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. A moistened dental wick was inserted into each sup to prevent drying and the i-cups were then covered. The cups were then held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on southern corn rootworm, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 6, 7, 9, 10, 11, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 35, 36, 38, 41, 42, 44, 45, 47, 48, 49 and 51.
. , '~ :;, , ' ' , , ' . , ,: .- ,7 ', :' .: .'' : `. ' . ', , ' ,.", . .~ ' '. ,, ' ' : ', , '' , ' ~' ~, '' .' ' " ': ' '' .. ' ' : ' ., ' , '' ,`. ,': ' .: . ' :: ' ' .: ' ' ' ~' . ' ~ :.
2~Q~6ti Example 60 Aster Leafhopper Test units were prepared from a series of 12-ounce cups, each containing oat (Avena sativa) seedlings in a l-inch layer of sterilized soil. Sets of three test units were sprayed as described in E~ample 56 with individual solutions of the below-listed compounds. After the oats had dried from the spraying, between 10 and 15 adult aster leafhoppers (Mascrosteles fascifroms) were aspirated into each of the cups. The cups were held at 27C and 50~ relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on aster leafhopper, the following resulted in greater than or equal to 80%
mortality: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 28, 30, 31, 35, 36, 38, 41, 42, 43, 44, 45, 47, 49, 50 and 51.
E~amDle 61 Boll Weevil Five adult boll weevils (Anthonomus prandis) were placed into each of a series of 9-ounce cups.
The test procedure employed was then otherwise the :
same as in E~ample 56 with three cups per treatment.
Mortality readings were taken 48 hours after treatment.
Of the compounds tested on boll wee~il, the following resulted in greater than or equal to 80%
mortality: 16, 21, 22, 23, 24, 25, 26, 27, 28, 30, 35, 36, 38, 41, 42~ 43, 44, 46, 48, 49, 50, 51, 52 and ,, -. .. . . . . . ~ . . . . . . . .
... . . . . , . .. . - . . .
. . . .. -. .. . .. .,~ , - . ~ .. : . - . - .
,, , , , ::: : .
. . . ~ : .. . ~, . . .. - , . , . , .. ~, - :
. :; , , . ~ - . . . .. , . . . .. : . .. . . . . . ..
- . .: .: . . : : -- : . : - , .:
.
CF3 5-Cl NlCH(CH3)2]Co2Et .
16 CF3 5-Cl N(CH3)CO2Et , .-, ~: . ., . , - . . ~ ; .. .. :
.. : - . ~: .. , . ~ , , , , . :, . , , :
.: , ....... ...~ . : , . ::
- ~ . .. : . . . ~ . .. : :: : , , . :
2noQ~6s CMPD Rl R2 Y
17 CF3 S-Cl N(cH3) 18 CF3 4-F CO29-Bu 19 CF3 5-Cl N(CH3) C02n-BU
CF3 5-Cl N[CH3(CH3) 2 ] C02n-Bu 1021 CF3 5-Cl N(cH3)co2n-dodecyl ~ .
22 CF3 5-Cl NtcH3)co2cyclohe~
23 CF3 5-Cl N(CH3)CO2(CH2)2OB
24 CF3 5 Cl N(CH3)cO2cl4H29 CF3 5-Cl N(CH3)cO2cl6H33 1526 CF3 5-Cl N(CH3)cO2cl8H37 27 CF3 5-Cl N(CH3)cO2c22H45 28 CF3 5-Cl N(CH3)Co2(cH2)2o(cH2)2oBu `
h ~ ~ Rl ' O SY .~:.
~ ... .
,:
: ':
. .
~:
', -.
.. . . : .: ~- , ' :.. , : . .. . . ~
2CIO~L6~;
5 CMPD Rl R2 R3 Y
29 CF3 4-C1 4-F N[cH(cH3)2]co2Et 31 CF3 4-C1 4-F N~cH(cH3)2]co2Bu 32 ~F3 4-C1 4-F N[CH(CH3)CH2CH3]CO2Et 33 CF3 4-C1 4-F CO2s-Bu 34 CF3 4-C1 4-F N(CH3)CO2cyclohe~yl 1 5 j~R~, R2 /~ .
N~N/
O~ ~, ~ R
CMP~ Rl R2 R3 Q
CF3 4-C1 4-Cl SN[cH(cH3)2]co2Et CF3 4-C1 4-Cl SN(cH3)co2~-Bu 30 36 CF3 4-C1 4-Cl SCO2s-Bu 37 Cl 4-C1 4-Cl SCO2s-Bu : . .
38 CF3 4-C1 4-Cl CO2CH3 CF3 4-C1 4-Cl SN[CH~CH3)2]cO2Et 35 41 CF3 4-C1 4-Cl COCH3 43 Br 4-C1 4-F COCH3 :
. . .
.
~ :
2C10Q~6S
~"
CMPD Rl R2 R3 Q
CF3 4-C1 4-F COPh 4 6 CF3 4-C1 4-Cl COCH2CH3 10 47 CF3 4-C1 4-Cl COCOCH2CH3 48 CF3 4-C1 4-Cl COn-Bu .
49 Cl 4-C1 4-Cl COCH3 Cl 4-C1 4-Cl COCH2CH3 ; .
51 Cl 4-C1 4-Cl C2CH3 15 52 CF3 4-C1 4-Cl CO-4-Cl-Ph 5 3 CF3 4 -C 1 4 -C 1 COt -Bu 54 CF3 4-C1 4-Cl CO2Ph , ~i . ::. .:, - . . :. . .
::
:,- : , , i . , . :
- \
2(10Q~L65 E~
Fall Armyworm Test units, each consisting of an 8-ounce plastic cup containing a layer of wheat germ diet, approx. 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (Spodoptera frugiperda~ were placed into each cup. Solutions of each of the test compounds (acetone/distilled water 75/25 solvent) were sprayed onto the cupsj a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which 15 discharged the spray at a rate of 0.5 pounds of :
active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. The cups were then covered and held at 27C
and 50% relative humidity for 72 hours, after which time mortality readings were taken.
Of the compounds tested on fall armyworm, the following resulted in greater than or equal to 80%
mortality: 1, 2, 9, 5, 6, 7, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41,-42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, and 54.
Example 57 Tobacco Budworm The test procedure of E~ample 56 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) except that mortality was assessed at 98 hours. Of the compounds tested on tobacco budworm, the fiollowing resulted in greater than or equal to 80% mortality: 2, 4, 7, 11, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 38, 41, 42, 43, 44, 45, 46, `
48, 49, 50, 51, 52, 53 and 54.
- . ~ ,, , , . , : ................. . . . , - ., . , . . -:, : : . : .
Z~Q~L65 ~alnple ~
European Corn Borer Test units, each ~onsisting of an 8-ounce plastic cup containing a one-inch square of wheat germ~soyflour diet, were prepared. Five third-instar larvae of the European corn borer (Ostrinia nubilalis) were placed into each cup. Sets of three test units were sprayed as described in E~ample 56 with indi-vidual solutions of the test compounds. The cups were then covered and held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested on European corn borer, the following resulted in greater than or equal to 80% mortality: no testing.
E~ample 59 Southern Co~n Rootworm Test units, each consisting of an 8-ounce plastic containing 1 sprouted corn (Zea mays) see, were prepared. Sets of three test units were sprayed as described in E~ample 56 with individual solutions of the test compounds. After the spray on the cups had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. A moistened dental wick was inserted into each sup to prevent drying and the i-cups were then covered. The cups were then held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on southern corn rootworm, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 6, 7, 9, 10, 11, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 35, 36, 38, 41, 42, 44, 45, 47, 48, 49 and 51.
. , '~ :;, , ' ' , , ' . , ,: .- ,7 ', :' .: .'' : `. ' . ', , ' ,.", . .~ ' '. ,, ' ' : ', , '' , ' ~' ~, '' .' ' " ': ' '' .. ' ' : ' ., ' , '' ,`. ,': ' .: . ' :: ' ' .: ' ' ' ~' . ' ~ :.
2~Q~6ti Example 60 Aster Leafhopper Test units were prepared from a series of 12-ounce cups, each containing oat (Avena sativa) seedlings in a l-inch layer of sterilized soil. Sets of three test units were sprayed as described in E~ample 56 with individual solutions of the below-listed compounds. After the oats had dried from the spraying, between 10 and 15 adult aster leafhoppers (Mascrosteles fascifroms) were aspirated into each of the cups. The cups were held at 27C and 50~ relative humidity for 48 hours, after which time mortality readings were taken.
Of the compounds tested on aster leafhopper, the following resulted in greater than or equal to 80%
mortality: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 28, 30, 31, 35, 36, 38, 41, 42, 43, 44, 45, 47, 49, 50 and 51.
E~amDle 61 Boll Weevil Five adult boll weevils (Anthonomus prandis) were placed into each of a series of 9-ounce cups.
The test procedure employed was then otherwise the :
same as in E~ample 56 with three cups per treatment.
Mortality readings were taken 48 hours after treatment.
Of the compounds tested on boll wee~il, the following resulted in greater than or equal to 80%
mortality: 16, 21, 22, 23, 24, 25, 26, 27, 28, 30, 35, 36, 38, 41, 42~ 43, 44, 46, 48, 49, 50, 51, 52 and ,, -. .. . . . . . ~ . . . . . . . .
... . . . . , . .. . - . . .
. . . .. -. .. . .. .,~ , - . ~ .. : . - . - .
,, , , , ::: : .
. . . ~ : .. . ~, . . .. - , . , . , .. ~, - :
. :; , , . ~ - . . . .. , . . . .. : . .. . . . . . ..
- . .: .: . . : : -- : . : - , .:
.
Claims (5)
1. A compound of the formula:
wherein R1, R2, and R3 are independently selected from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, S(O)R4, S(O)2R4, OC(O)R4, OS(O)2R4 CO2R4 C(O)R4, C(O)NR4R5, S(O)2NR4R5, NR4R5, NR5C(O)R4, OC(O)NHR4, NR5C(O)NHR4 and NR5S(O)2R4; or when m, n or p is 2, R1, R2, or R3 can independently be taken together as OCH2O, OCH2CH2O or CH2CH2O, to form a 5- or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups, R3 being other than C(O)2R4, C(O)R4, S(O)2NR4R5 or C(O)NR4R5;
R4 is selected from H, C1 to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, C1 to C6 haloalkyl, C3 to C6 haloalkenyl, C1 to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally substituted with W; or R4 and R5 can be taken together as (CH2)4, (CH2)5 or CH2CH2OCH2CH2;
R5 is selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or C1 to C4 halo-alkyl;
m, n and p are independently 1 to 3;
W is halogen, CN, NO2, C1 to C2 alkyl, C1 to C2 haloalkyl, C1 to C2 alkoxy, C1 to C2 halo alkoxy, C1 to C2 alkylthio, C1 to C2 halo-alkylthio, C1 to C2 alkylsulfonyl or C1 to C2 haloalkylsulfonyl;
Q is C2 to C22 alkoxycarbonyl, C2 to C22 haloalkoxycarbonyl, C7 to C15 phenoxycarbonyl optionally substituted with 1 to 3 substi-tuents selected from W; C7 to C15 phenyl-carbonyl optionally substituted with 1 to 3 substituents independently selected from W;
C2 to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben-zyloxycarbonyl optionally substituted with 1 to 3 substituents independently selected from W.
wherein R1, R2, and R3 are independently selected from R4, halogen, CN, N3, SCN, NO2, OR4, SR4, S(O)R4, S(O)2R4, OC(O)R4, OS(O)2R4 CO2R4 C(O)R4, C(O)NR4R5, S(O)2NR4R5, NR4R5, NR5C(O)R4, OC(O)NHR4, NR5C(O)NHR4 and NR5S(O)2R4; or when m, n or p is 2, R1, R2, or R3 can independently be taken together as OCH2O, OCH2CH2O or CH2CH2O, to form a 5- or 6-membered ring, each of which can be independently substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups, R3 being other than C(O)2R4, C(O)R4, S(O)2NR4R5 or C(O)NR4R5;
R4 is selected from H, C1 to C6 alkyl, C3 to C6 cycloalkyl, C3 to C8 alkoxycarbonylalkyl, C3 to C6 alkenyl, C3 to C6 alkynyl, C1 to C6 haloalkyl, C3 to C6 haloalkenyl, C1 to C6 alkyl substituted with CN, CO2CH3, CO2CH2CH3, OCH3, OCH2CH3, SCH3, SCH2CH3 or NO2, or R4 is phenyl or benzyl, either optionally substituted with W; or R4 and R5 can be taken together as (CH2)4, (CH2)5 or CH2CH2OCH2CH2;
R5 is selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, C3 to C4 alkynyl or C1 to C4 halo-alkyl;
m, n and p are independently 1 to 3;
W is halogen, CN, NO2, C1 to C2 alkyl, C1 to C2 haloalkyl, C1 to C2 alkoxy, C1 to C2 halo alkoxy, C1 to C2 alkylthio, C1 to C2 halo-alkylthio, C1 to C2 alkylsulfonyl or C1 to C2 haloalkylsulfonyl;
Q is C2 to C22 alkoxycarbonyl, C2 to C22 haloalkoxycarbonyl, C7 to C15 phenoxycarbonyl optionally substituted with 1 to 3 substi-tuents selected from W; C7 to C15 phenyl-carbonyl optionally substituted with 1 to 3 substituents independently selected from W;
C2 to C22 alkyl carbonyl, C2 to C22 haloalkyl carbonyl, CHO, C(O)CO2R5, or C8 to C12 ben-zyloxycarbonyl optionally substituted with 1 to 3 substituents independently selected from W.
2. A compound according to Claim 1 wherein:
R1, R2, and R3 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2;
R1, R2, and R3 can be taken together as OCH2O, OCH2CH2O or CH2CH2O, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is C1 to C2 alkyl, C3 to C4 alkenyl, C1 to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or C1 to C2 alkyl;
Q is CHO, C2 to C6 alkoxycarbonyl, C2 to C6 haloalkoxycarbonyl, C2 to C6 alkyl-carbonyl, C2 to C4 haloalkylcarbonyl, C7 to C10 phenoxycarbonyl, C7 to C10 phenylcarbonyl or C8 to C10 benzyloxy-carbonyl each phenoxy, phenyl or benzyl-oxy group optionally substituted with 1 to 2 substituents selected from W; and a is 2.
R1, R2, and R3 are independently R4, CO2R4, halogen, CN, NO2, OR4, SR4, S(O)R4, S(O)2R4 or NR4R5, or when m, n or p is 2;
R1, R2, and R3 can be taken together as OCH2O, OCH2CH2O or CH2CH2O, each of which can be substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups;
R4 is C1 to C2 alkyl, C3 to C4 alkenyl, C1 to C2 haloalkyl, C3 to C4 haloalkenyl or phenyl optionally substituted with halogen;
R5 is H or C1 to C2 alkyl;
Q is CHO, C2 to C6 alkoxycarbonyl, C2 to C6 haloalkoxycarbonyl, C2 to C6 alkyl-carbonyl, C2 to C4 haloalkylcarbonyl, C7 to C10 phenoxycarbonyl, C7 to C10 phenylcarbonyl or C8 to C10 benzyloxy-carbonyl each phenoxy, phenyl or benzyl-oxy group optionally substituted with 1 to 2 substituents selected from W; and a is 2.
3. A compound according to Claim 2 wherein:
R1 is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, OCF2CF2H, CF3 or when m is 2 then R1 may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring, R2 and R3 are independently selected from H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
Q is C2 to C4 alkoxycarbonyl, C2 to C4 alkylcarbonyl, C7 to C8 phenylcarbonyl or CHO; and m, n or p are independently 1 to 2 and one substituent is in the 4-position.
R1 is halogen, CN, NO2, OCF2H, OCF3, OCH2CF3, OCF2CF2H, CF3 or when m is 2 then R1 may be taken together as CH2C(CH3)2O or CF2CF2O to form a 5 membered ring, R2 and R3 are independently selected from H, halogen, CN, NO2, OCH3, OCF2H, OCH2CF3, OCF3, SCH3, SCF2H, SCF3, CF3, OCF2CF2H or phenoxy;
Q is C2 to C4 alkoxycarbonyl, C2 to C4 alkylcarbonyl, C7 to C8 phenylcarbonyl or CHO; and m, n or p are independently 1 to 2 and one substituent is in the 4-position.
4. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to any one of Claims 1 to 3 and a carrier therefor.
5. A method for controlling arthropods comprising applying to them or to their environment an arthropodicidally effective amount of a compound according to any one of Claims 1 to 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30401189A | 1989-01-25 | 1989-01-25 | |
| US394,011 | 1995-03-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2000165A1 true CA2000165A1 (en) | 1990-07-25 |
Family
ID=23174644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2000165 Abandoned CA2000165A1 (en) | 1989-01-25 | 1989-10-04 | N-sulfenylated and n-acylated pyrazolines |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2000165A1 (en) |
-
1989
- 1989-10-04 CA CA 2000165 patent/CA2000165A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2669933B2 (en) | Arthropodicidal carboxyanilides | |
| EP0330678B1 (en) | Insecticidal pyrazolines | |
| US5091405A (en) | Insecticidal pyrazolines | |
| US5474998A (en) | Arthropodicidal pyrazolines, pyrazolidines and hydrazines | |
| JP2894363B2 (en) | Substituted semicarbazone arthropod control agents | |
| JP2001097956A (en) | Anilide having arthropod-killing property | |
| JP3030081B2 (en) | Arthropodic tetrahydropyridazines | |
| US5116850A (en) | Heterocyclic pyrazoline carboxanilides | |
| EP0365155B1 (en) | N-sulfenylated and N-acylated pyrazolines | |
| US5369121A (en) | Arthropodicidal pyrazolines, pyrazolidines and hydrazines | |
| US5196408A (en) | N-sulfenylated pyrazolines, compositions and use | |
| US5276039A (en) | Substituted indazole arthropodicides | |
| US5591764A (en) | N-acylated pyrazolines | |
| CA2000165A1 (en) | N-sulfenylated and n-acylated pyrazolines | |
| EP0322126A1 (en) | Heterocyclic pyrazoline carboxanilides | |
| US5491162A (en) | N-acylated pyrazolines, compositions and use | |
| CA2011094A1 (en) | Arthropodicidal tetrahydrobenzopyranopyrazoles | |
| US4790869A (en) | Sulfonamide compounds and salts thereof, herbicidal compositions containing them | |
| CA2000130A1 (en) | N-sulfenylated and n-acylated pyrazolines | |
| CA2075382A1 (en) | Arthropodicidal trichloromethylbenzylamines | |
| WO1994024111A1 (en) | Arthropodicidal and nematocidal triazoles | |
| CA2005740A1 (en) | Substituted semicarbazone arthropodicides | |
| JPH05501708A (en) | Arthropodicidal pyrazolines | |
| CA2000129A1 (en) | Substituted indazole arthropodicides | |
| WO1994025440A1 (en) | Arthropodicidal and nematocidal heterocyclic sulphonates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |