CA1339315C - 5h-imidazopyrrolopyridine, quinoline, thieno- and furopyridine, dihydrothieno- and furopyridine 2-5-diones - Google Patents

Abstract

This invention concerns compounds of the formulae (see fig.I) and (see fig.II) useful as intermediates in preparation of dihydroimidazo-pyrrolopyridines, quinolines, thieno- and furo[2,3-b]pyridines which have utility as herbicides. In these compounds R1 and R2 may represent such radicals as C1-C3 alkyl or cyclopropyl, X may represent halogen, hydrogen or methyl and Y and Z may be such radicals as hydrogen, halogen, alkyl, alkoxy, phenoxy, nitro, cyano or Y and Z when taken together may form an additional ring which may be heterocyclic.

Description

-1- 13393 1~
5H-IMIDAZOPYRROLOPYRIDINE, QUINO1INE, THIENO- AND
FUROPYRIDINE, DIHYDROTHIENO- AND FUROPYRIDINE 2-5-DIONES
This application is a divisional application of application Serial No. 460,029 filed on July 31st, 1984.
The invention of the parent application relates to novel herbicidally effective, dihydroimidazopyrrolopyridines and derivatives thereof which are useful for the control of undesirable monocotyledonous and dicotyledonous plant species. The invention of the parent application also relates to a process for the preparation of said herbicidally effective compounds.
More particularly, the invention of the parent application relates to novel,herbicidally effective, dihydroimidazopyrrolopyridines, quinolines, thieno- and furo[2,3-b]pyridines, dihydrothieno- and furo[2,3-b]pyridines, thieno- and furo[3,2-b]pyridines and dihydrothieno- and furo[3,2-b]pyridines depicted by formula (I) below:

1339~1~

R l Y~' ~ R 2 Z w N N

wherein Rl and R2 each represent Cl-C3 alkyl or cyclo-propyl, with the proviso that the sum of the number of carbon atoms in Rl and R2 is 2 to 5; and when Rl and R2 are taken together with the carbon to which they are attached, they may form a C3-C6 cycloalkyl ring optionally substituted with methyl;
W is oxygen or sulfur;
A is hydrogen, hydroxyl, C3-C6 alkenyloxy, C3-C6 alkynyl-oxy, Cl-C6 alkylthio, NR13R14 or Cl-C6 alkoxy optionally substituted with phenyl, halophenyl, Cl-C3 alkylphenyl, Cl-C3 alkoxy-phenyl or di-Cl-C3 alkylaminophenyl;
R13 is hydrogen, Cl-C4 alkyl optionally substituted with phenyl, halophenyl, Cl-C3 alkylphenyl or Cl-C3 alkoxyphenyl;
R14 is hydrogen or Cl-C4 alkyl;
X is hydrogen, halogen or methyl;

133~31~

Y and Z are each hydrogen, halogen, Cl-C6 alkyl, Cl-C4 hydroxyalkyl, Cl-C6 alkoxy, Cl-C4 alkyl-thio, phenoxy, Cl-C4 haloalkyl, OCF2CHF2, OCF3, OCHF2, nitro, cyano, NR4Rs, C3-Cg straight or branched alkenyloxy optionally substituted with one to three halogens, C3-Cg straight or branched alkynyloxy option-ally substituted with one to three halogens, or phenyl optionally substituted with one Cl-C4 alkyl, Cl-C4 alkoxy or halogen;
R4 is hydrogen or Cl-C4 alkyl;
Rs is Cl-C4 alkyl;
And, when taken together, Y and Z may form a ring in which YZ is represented by (1) the structure: -(CH2)n-, where n is an integer of 2, 3 or 4, provided that X is hydrogen; or (2) by the structure: -C~=IC-lC-lC-where, L, M, R7 and R8 each represent hydro-gen, halogen, Cl-C4 alkyl, Cl-C4 alkoxy, Cl-C4 alkylthio, Cl-C4 alkylsulfonyl, Cl-C4 haloalkyl, NO2, CN, phenyl, phenoxy, amino, OCF3, OCHF2, OCF2CHF2, Cl-C4 alkylamino, dialkyl(Cl-C4)amino, chlorophenyl, methyl-phenyl, C3-Cg straight or branched alkenyl-oxy optionally su.bstituted with one to three halogens, c3-cg straight or branched alkynyloxy optionally substituted with one 3~ to three halogens, or phenoxy substituted with one Cl, CF3, NO2 or CH3 group, with the proviso that only one of L, M, R7 or R8 may represent a substituent other than hydrogen, halogen, Cl-C4 alkyl or Cl-C4 alkoxy; or (3) by the structures:
-C=IC-B-, -B-C=IC- , -CH-ICH-B-, or -B-CH-CH-;
RloRg ~gRlo R12~11 RllR12 where B is oxygen or sulfur; Rg and Rlo each represent hydrogen, halogen, phenyl, or Cl-C4 alkyl; Rll and R12 each represent hydrogen, Cl-C4 alkyl or phenyl;
and when Rl and R2 are not the same, the cis- or trans-isomers or mixtures thereof or the optical isomers (cis- or trans- or mixtures thereof).
As used in the present specification and claims, the term "halogen" means F, Cl, Br or I, unless otherwise specified.
It should, of course, be understood that when Rl and R2 are not the same, the formula (I) compounds can exist as both the cis- and trans-isomers. These can be illustrated as follows:

~N~--'1ll R2 Z W
N N
A H
(Ia) cis, and X
Y ~ N - I
~I R 2 Z~\ J~ W
N - N
A H

(Ib) tran 5 .

Especially preferred compounds of the present invention are more precisely illustrated by formulas II, III, IV, V, VI, VII and VIII shown below.
Preferred dihydroimidazopyrrolopyridine com-pounds of this invention are depicted by formula (II), hereinafter illustrated:
R I

Y~ N R2 Z J ~ W
N ' N

( I I ) wherein A, Rl, R2, W and X are as defined in reference to formula I above; Y and Z each, independently, rep-resent hydrogen, halogen, Cl-C6 alkyl, Cl-C6 alkoxy, CN, N02, OCF3, OCHF2, OCF2CHF2, phenoxy, Cl-C4 halo-alkyl, Cl-C4 alkylthio, Cl-C4 hydroxyalkyl, NR4Rs, C3-Cg straight or branched alkenyloxy optionally sub-stituted with one to three halogens, C3-Cg straight or branched alkynyloxy optionally substituted with one to three halogens, or phenyl optionally substituted with one Cl-C4 alkyl, Cl-C4 alkoxy or halogen; R4 is hydrogen or Cl-C4 alkyl; Rs is Cl-C4 alkyl; and when taken toge-ther Y and Z may form a ring in which YZ are represented by the structure: -(CH2)n-, where n is an integer of 2, 3 or 4; and when Rl and R2 are not the same, the cis-or trans-isomers or mixtures thereof or the optical isomers (cis- or trans- or mixtures thereof).

1~39~1~

Preferred dihydroimidazopyrroloquinolines are illustrated by formula (III):

R ~ J : w N N
A H

(III) wherein A, Rl, R2, W and X, are as defined above in reference to formula I, and L, M, R7 and R8 represent lS hydrogen, halogen, Cl-C4 alkyl, Cl-C4 alkoxy, Cl-C4 alkylthio, Cl-C4 alkylsulfonyl, Cl-C4 haloalkyl, N02, CN, phenyl, phenoxy, amino, CF3, OCHF2, OCF2CHF2, Cl-C4 alkylamino, dialkyl(Cl-C4)amino, chlorophenyl, methyl-phenyl, C3-Cg straight or branched alkenyloxy option-20 ally substituted with one to three halogens, C3-Cg straight or branched alkynyloxy optionally substituted with one to three halogens, or phenoxy substituted with one Cl, CF3, NO2 or CH3 group, with the proviso that only one of L, M, R7 or Rg, may represent a substituent 25 other than hydrogen, halogen, Cl-C4 alkyl or Cl-C4 alkoxy; and when Rl and R2 are not the same, the cis-or trans-isomers or mixtures thereof or the optical isomers (cis- or trans- or mixtures thereof).

Preferred dihydroimidazopyrrolothieno- and furo[3,2-b]pyridines and dihydroimidazopyrrolodihydro-thieno- and furo[3,2-b]pyridines are, respectively, 5 illustrated by formulas (V) and (VI), shown below:

,1~ R 1 R 10~ /)~\ W
N N
A H

(V) and, R
Rll ~ ~ W

A H

( V I ) wherein A, Rl, R2, W and B, are as defined above in reference to formula I; Rg and Rlo each represent hydrogen, halogen, Cl-C4 alkyl or phenyl; and Rll and R12 each represent hydrogen, Cl-C4 alkyl or phenyl; and 25 when Rl and R2 are not the same, the cis- or trans-isomers or mixtures thereof or the optical isomers (cis- or trans- or mixtures thereof).
The preferred dihydroimidazopyrrolothieno-and furo[2,3-b]pyridines and the dihydroimidazopyrrolo-30 dihydrothieno- and furo[2,3-b]pyridines are, respecti-vely, depicted by formulas (VII) and (VIII) illustrated as follows:

133931~

~ Rl R10.~ ~ R2 Rg W
B N - N
A H

(VII ) and, R12~ ~ Rl R2 Rll W
B N N
A H

( V I I I ) wherein A, Rl, R2, W and B, are as defined above in 20 reference to formula I, Rg and Rlo each represent hydrogen! halogen, Cl-C4 alkyl or phenyl; Rll and R12 each represent hydrogen, Cl-C4 alkyl or phenyl; and when Rl and R2 are not the same, the cis- or trans-isomers or mixtures thereof or the optical isomers 25 (cis- or trans- or mixtures thereof).
It is obvious that in the case of formula (VI) and (VIII) that when either Rll or R12 is other than hydrogen, additional optical and cis- and trans-isomers are possible, and all of these are considered to be within the scope of the invention.

133931~
g Although dihydroimidazoisoindolediones are described as herbicidal agents in United States Patent 4,041,045 issued August 9, 1977, said publication does not render the compounds of this invention obvious since it does not disclose or imply the disclosure of herbicidal compounds containing a pyridine or substituted pyridine ring. Moreover, it is surprising to find that the formula I compounds of this invention are frequently found to be highly selective herbicidal agents effective for the preemergence and postemergence control of a wide variety of undesirable broadleaf weeds and grasses in the presence of graminaceous crops such as corn, rice and wheat; leguminous crops such as soybeans and in the presence of a variety of other crops including cotton.
In accordance with the process of the present invention, the novel formula (I) dihydroimidazopyr~olo-pyridines, quinolines and the like can be prepared by reaction of the appropriately substituted or unsubsti-tuted formula (XII) 2-(2-imidazolidinyl)nicotinic acid;
2-(2-imidazolidinyl)quinoline-3-carboxylic acid; 2-(2-imidazolidinyl)thieno- or furo[3,2-b]pyridine-6-carbo-xylic acid; 2-(2-imidazolidinyl)dihydrothieno- or furo-[3,2-b]pyridine-6-carboxylic acid; 2-(2-imidazolidinyl)-thieno- or furo[2,3-b]pyridine-5-carboxylic acid or 2-(2-imidazolidinyl)dihydrothieno or furo[2,3-b]pyridine-5-carboxylic acid, with at least one molar equivalent and preferably a slight excess of acetic anhydride in the presence of pyridine and acetonitrile.

~ 1~3931~
- 1 o -In practice, it is generally desirable to warm the reaction mixture to about 40 to 60~C until an essen-tially clear solution is obtained. Cooling of the thus-prepared solution to about ambient temperature or below then yields the desired formula (I) dihydroimidazo-pyrrolopyridine, quinoline, thieno or furo-pyridlne or dihydrothieno or furopyridine, corresponding to the isomeric mixture of the substituted or unsubstituted acid employed as starting material for the reaction.
The reaction may be graphically illustrated as follows:

l_ y ~ OOH

N N R2 + ~ +
HN - W
(XII) (CH3C0)2o l I
Z~\, ~ ~=W
N , N

(I) wherein X, Y, Z, Rl, R2 and W are as described for 3~ formula (I) above.

Similarly, in an alternate procedure it has also been found that the substituted or unsubstituted 2-(2-imidazolidinyl)nicotinic acid; 2-(2-imidazoli-dinyl)quinoline-3-carboxylic acid; 2-(2-imidazolidinyl)-thieno- or furo[3,2-b]pyridine-6-carboxylic acid; 2-(2-imidazolidinyl)dihydrothieno- or furo[3,2-b]pyridine-6-carboxylic acid; 2-(2-imidazolidinyl)thieno- or furo-[2,3-b]pyridine-5-carboxylic acid or 2-(2-imidazo-lidinyl)dihydrothieno- or furo[2,3-b]pyridine-5-carbo-xylic acid, which are themselves pre- and postemergence herbicides, can be converted to the corresponding formula (I) dihydroimidazopyrrolopyridine, quinoline, thieno- or furo[3,2-b]pyridine, dihydrothieno- or furo-[3,2-b]pyridine, thieno- or furo[2,3-b]pyridine or the dihydrothieno- or furo[2,3-b]pyridine, by reaction thereof with at least an equimolar amount of N,N'-dicyclohexylcarbodiimide in the presence of a chlori-nated hydrocarbon solvent such as methylene chloride, dichloroethane, chloroform or the like. The reaction may be conducted at ambient temperature and yields the desired formula (I) compound on evaporation or separa-tion of the solvent from the reaction mixture. The reaction may be graphically illustrated as follows:

133931~

Y~COOH
N ~ N--R2 + ~N=C=~3 HN--W

(X~ I I ) ~ R 1 Z W
N . N
~ H
( I ) wherein R1, R2, X, Y, Z and W are as described with respect to formula (I) above. It should be understood that if a cis-, trans- or mixture of cis- and trans-imidazolidinone is employed as starting m~terial in the above reactions, then the cis-, trans- or mixture of cis- and trans- formula (I) compounds is obtained.
These formula (I) dihydroimidazopyrrolopyridines, quino-lines, thieno- and furopyridines and dihydrothieno- and furopyridines, are unexpectedly substantially more selective than their 2-(2-imidazolidinyl)acid precursors.

~ 1339315 Many of the formula (I) dihydroimidazopyrrolo-pyridine, quincline, thieno- and furopyridine and dihydrothieno- and furopyridine, compounds of the present invention may also be prepared by reduction of the corres-ponding formula (XIV) 5H-imidazopyrrolopyridine, quinoline, thieno- or furopyridine, or dihydrothieno- or furopyridine, 2,5-dione. This reduction can be achieved by reaction of the formula (XIV) 2,5-dione with at least an equimolar amount of a reducing agent such as sodium or lithium borohydride in alcohol or aqueous alcohol or tetrahydrofuran or aqueous tetrahydrofuran, at a temperature between about -10 and +5~C. Acidification of the reaction mixture to a pH of about 3, using a strong mineral acid such as concentrated sulfuric acid, then yields the desired formula (I) product. The reaction may be graphically illustrated as follows:

b~ R l y ~ / ~ N R2 + NaBH4 (XIV) Z~\ J~, W
N N

' R 1 11 . (I) Z--N - N
H H

The compounds of formula (XIV) and their isomers in which R
and R2 have exchanged positions with W form the subject of this divisional application.

133931~

wherein X, Y, Z, W, Rl and R2 are as described with respect to formula (I) above.
-This procedure usually forms a mixture of the cis and trans-isomers of the formula (I) compounds.
The preparation of the formula XIV 5H-imidazo-pyrrolopyridines and imidazopyrroloquinolines in which W is oxygen is described in the European Patent Appli-cation 0,041,623, published December 16, 1981.
In all the cases described above, the products 10 from the reaction are those in which A is hydrogen. In order to prepare these compounds in which A is a group other than hydrogen, advantage is taken of the ability of the /C=N- function in the imidazopyraolopyridines, quinolines, thieno- and furopyridines to add a variety of nucleophiles such as alcohols, amines and thiols.
The reaction may be graphically illustrated as follows:

X R
Y ~ Rl l I + AH
Z--~ / ~\\ W
N N

Z~\~
W
N A HN

-15- 133931~

wherein AH is, for example, CH30H, CH3SH, CH3NH2. This reaction may be catalyzed by acids such as ~-toluene-sulfonic acid or bases such as tertiary amines.
In practice it has been found that many sub-stituted and unsubstituted aromatic and heteroaromatic imidazolidinone and imidazolidinethione compounds utilized as starting materials for the above described reactions by formula (I) can be prepared by reduction of the corresponding formula (XV) imidazolinone or 1 imidazolinethione with, for example, at least about an equimolar amount of sodium cyanoborohydride in the presence of a solvent such as Cl-C4 aliphatic alcohol, aqueous alcoholic mixture or ether, followed by acidi-fication to a pH between about 2.5 and 5 and preferably between 3 and 4, with a strong mineral acid such as hydrochloric acid, or an organic acid such as acetic or the like. This reduction is generally conducted at a temperature between 0 and 40~C and is particularly effective for treatment of 2-(2-imidazolinyl)nicotinic acids and esters, but preferably the methyl esters. It is likewise effective for reduction of the imidazolinyl function 2-(2-imidazolinyl)thieno and furo[3,2-b]-pyridine-6-carboxylic acid esters and 2-(2-imidazolinyl)-thieno and furo[2,3-b]pyridine-5-carboxylic acid esters.
The above described reduction may be graphic-ally illustrated as follows:

-16- 13393 ~5 X X
Y~\ :OOR Y~\~ COOR
I R NaCNBH3 ll H R Cis 5z~\ ~ \~/ N R2 Z--~N ~/ N ~ ll HN =W HN ',~/

(XV) +
X

Y~CO O R
Z~ ?~ H R 1 Tran 5 H N~',~l wherein ~ may be hydrogen, but preferably a methyl group and Rl, R2, W, X, 'f and Z, are 2s defined in reference to sai.d formula I. When R is a methyl group then this can advantageously be removed by reaction of the methyl ester in a C1-C4 aliph21ic alcohol, prefer-ably absolute methanol, and admixing therewith at least one equivalent of strong base.
As shown above, the imidazolidinones and 25 imidazolidinethiones are obtained as a mixture of cis-and trans-isomers when Rl and R2 are not the same.
These isomers are obtained in vari2ble amounts. The mixtures are useful as such, but can frequently be - separ2ted chromatographic211y to give the pure cis- and trans-isomers, both of which are effective herbicidal agents.

133~31~
-l7-Since the above-described reduction is not a universal method for the prep2ration of all substituted and unsubstituted aromatic and heteroaromatic imidazo-lidinones and imidazolidinethiones, a variety of synthetic routes have been explored in order to provide effective procedures for the manufacture of the imid2zo-lidinones and imidazolidinethiones employed as starting materials for the preparation of the formula (I) compounds of this invention.
Accordingly, it has now been determined that both the oxo and thioxo derivatives of 2-(2-imidazoll-dinyl)nicotinates and 2-(2-imidazolidinyl)quinoline-3-carboxylates can be synthesized by heating to refluxing temperature, a mixture of a formula IX aminoamide or aminothioamide with about an equimolar amount of an appropriate formula X substituted or unsubstituted lower alkyl, 2-formylpyridine-3-carboxylate or 2-formyl-quinoline-3-carboxylate, in the presence of an inert organic solvent such as benzene, toluene, or the like, and a strong organic acid, such as p-toluenesulfonic acid, under a blanket of nitrogen. The thus-formed ester may then be converted to the corresponding formula (XII), acid, used as starting materials in the syntnesis of the formula (I) compounds of the present inventicn, by dissolving or dispersing the imidazolidinone ester or imidazolidinethione ester in a C--C4 aliphatic alcohol, preferably absolute methanol and admixing therewith at least one equivalent of strong base.

133931~

In practice, the base is generally dissolved in water and the mixture heated to between about 20 and 50~C.
The mixture is then cooled and adjusted to pH 6.5 to 7.5, and preferably about pH 7, with a strong mineral acid such as hydrochloric acid to yield the imidazo-lidinone or imidazolidinethione acid wherein Rl, R2, - R3, W, X, 'f and Z are as defined above. The reaction is illustrated in Flow Diagram (I).

3o -19- 133~31S

F L OW D I AGRAM

Y ~:O O R ~1 ~
I + NH2--C, ~--NH2 Z--\\N /--CHO R2 (X) ( IX) X X pTSA

Y~--COOR + Y~COOR
z~\\ ~ H Rl N ~ N ~

H N ~ H N ~,~/

Tran s Ci 5 ( L I I a ) ( L I I b ) 1. CH30H/NaOH
2. Acid Y~COOH

N ~ N--R 2 H N =W
3o ( X I I ) 133~315 wherein R is Cl-C4 alkyl; and Rl, R2, X, Y, Z and W are as described for formula (I) above.
- The reaction of an aldehyde of formula (X) with an ~-aminoamide or thioamide of formula (IX) under acid catalysis gives the corresponding Schiff's base as the initial product. Whether the Schiff's base of general formula X

Y~ ~C O O R ~1 W
Z~, ~: H=N~ ~--N H 2 is isolated as such or cyclizes under the reaction conditions to the desired imidazolidinone depends on some unknown subtle factors. Nevertheless, if the Schiff's base is isolated it can, in a separate reaction, be cyclized with trifluoroacetic acid to the imidazo-lidinone.
Substituted Cl-C4 alkyl 2-formylnicotinates which are useful in the preparation of 2-(2-imidazoli-dinyl)nicotinatic acids and esters by the aldehyde route described above and illustrated in Flow Diagram I, for synthesis of formula LIIa and LIIb substituted 5-oxo-2-imidazolidinyl nicotinates and the formula (XII) acids, can be prepared from substituted Cl-C12 alkyl 2-methylnicotinates. For convenience and clarity, the following synthesis is described using substituted methyl 2-methylnicotinates as illustrative of this . class of reactions.

In accordance with the process, equivalent amounts of a substituted methyl 2-methylnicotinate, represented by formula LIII and m-chloroperbenzoic acid are admixed in the presence of a chlorinated hydrocarbon such as methylene chloride, chloroform or the like. The reaction mixture is heated to refluxing temperature, then cooled to ambient temperature and excess peracid destroyed by addition of excess l-hexene. Thereafter the solution is washed with sodium bicarbonate solution, dried and concentrated to give the corresponding sub-stituted methyl methylnicotinate l-oxide of formula LIV.
The formula LIV l-oxide is then heated to about 70 to 95~C with an excess of acetic anhydride to yield the formula LV substituted methyl 2-acetoxymethylnicotinate.
A cosolvent such as pyridine or pyridine/dimethoxyethane may also be used in the reaction, but is not essential.
Oxidation of the formula LV acetoxymethylnicotinate with hydrogen peroxide in acetic acid yields the methyl 2-acetoxymethylnicotina~e l-oxide represented by formula LVI. This l-oxide is then readily converted to the formula LVII methyl 2-diacetoxymethylnicotinate by reaction with an excess of acetic anhydride at a tem-perature between about 70 and 95~C, with or without a cosolvent such as pyridine or pyridine/dimethoxyethane.
Treatment of the formula LVII methyl diacetoxymethyl-nicotinate with an alkali metal alkoxide such as sodiummethoxide, sodium ethoxide, potassium butoxide, or the like, in the presence of a Cl-C4 aliphatic alcohol then yields the substituted alkyl formylnicotinate such as methyl 2-formylnicotinate of formula LVIII.

- 13393l~

Alternatively, it has also been found that the reaction of a substituted Cl-C12 alkyl 2-methyl-nicotinate, depicted by formula LIII, with benzaldehyde at an elevated temperature, yields the formula LIX
methyl 2-styrylnicotinate which, when ozonized gives the formula LVIII substituted alkyl formylnicotinate.
Additionally, it has been found that treat-ment of the formula LV substituted methyl 2-acetoxy-methylnicotinate with an alkali metal alkoxide such as sodium methoxide, in the presence of a lower aliphatic alcohol at an elevated temperature, yields the cor-responding substituted methyl 2-hydroxymethylnicotinate of formula LX. The substituted methyl 2-hydroxymethyl-nicotinate is then converted to the formula LVIII
substituted methyl formylnicotinate by oxidation with selenium dioxide or lead tetraacetate.
The above reactions are graphically illus-trated in Flow Diagram II.

FLOW DIAGRAM II

Y ~ OOCH3 ~ CHO

(LIII) Y ~ OOCH3 ~ Z H = CHC6H5 Y ~ COOCH3 N
Z ~ ~ ~ CH3 (LIX) +~
-O (LIV) o3 Y ~ OOCH3 Acetic anhydride z_ N {HO
tLVIII) X ~ X
Y ~ COOCH3 Y ~ OOCH3 I NaOMe/MeO H ll Z--N--CH20COCH3 Z-- ~ ~--CH20H
(LV) .(LX) H2o2 SeO2 or Pb(OAc)4 -24- 133~31S

FLOW DIAGRAM II (Continued) Y ~ OOCH3 Y ~ OOCH3 ~ (LVI) (LVIII) Acetic anhydride X

Y ~ OOCH3 H(OCOCH3)2 N
(LVII) CH30H, CH30Na X
y ~ OOCH3 N
(LVIII) 3o The reduction of quinolinic acid diesters with diisobutylaluminum hydride is also an effective route to alkyl 3-formylnicotinates. The synthesis of these quinolinic acid diesters is described in European Patent Application 81103638.3, Publication Number 0 041 623.
The aldehyde route to the preparation of the formula LIIa and LIIb substituted (5-oxo(and thioxo)-2-imidazolidinyl)nicotinates is likewise effective for the preparation of the substituted and unsubstituted (5-oxo-2-imidazolidinyl)quinoline-3-carboxylates from the substituted 2-formylquinoline-3-carboxylates.
The process for the preparation of these substituted 2-formylquinoline-3-carboxylate interme-diates involves the reaction of an appropriatelysubstituted aniline, depicted by formula LXI:

~R8 L~R7 M

( LXI ) wherein L, M, R7 and R8 are as defined in reference to formula III quinolines; with approximately an equimolar amount of a keto-ester depicted by formula LXII and having the structure:

R '--C0--CH2COOR "

(LXII) 13393l~

wherein R' is CH3 or COOR" and R" is C1-C4 alkyl. This reaction is optionally conducted in the presence of an organic sulfonic acid such as p-toluenesulfonic acid hydrate, camphorsulfonic acid, or aniline hydrochloride, in the presence of an organic solvent such as cyclo-hexane, toluene, benzene, xylene, monochlorobenzene, orthodichlorobenzene and mixtures thereof, or the like at a temperature from about 20 to 110~C. It is pre-ferred to continuously remove the water which is formed during the reaction by distillation either at atmospheric or under reduced pressures of as low as 50 mm of Hg while mzintaining the reaction temperature in a range of 75 to 80~C. The reaction yields the B-anilino-~,B-unsaturated ester of formula LXIII i.e., H~ { 00 R "
~ /C R

(LXIII)wherein L, M, Q, R7, R'j and R" are as described above.
The thus-formed B-anilino-~,B-unsaturated Z5 ester of formula LXIII is then reacted with an approxi-mately equimolar amount of ar; immonium salt having the structure:
e e Cl { H N ( R "' )2 Cl , 3o (LXIV) -27- ~ 1 339 31 5 wherein R~ is C1-C6 alkyl or ~ ~ e Cl - CH N (CH2)n Cl (LXIVa) wherein n is 4 or 5, and referred to respectively as formula LXIV or LXIIa. The reaction is conducted in the presence of a hydrocarbon solvent such as toluene or a chlorinated hydrocarbon solvent such as methylene chloride, dichloroethane, orthodichlorobenzene, chloro-benzene, or mixtures thereof, at a temperature between about 40 and 110~C, for a period of time sufficient to essentially complete the reaction and yield the formula LXV alkyl ester of 2-methyl-3-quinolinecarboxylic acid, if R' is CH3 in the formula LXVII B-anilino-~.B-unsaturated ester or the quinoline-2,3-dicarboxylate if R' is COOR" in the formula LXVIII B-anilino-~,B-unsatu-rated ester.
Alternatively, the formula LXI substituted 20 aniline, wherein L, M, R7 and R8 are as described above, can be reacted with about an equimolar amount of a formula LXVI acetylene dicarboxylate having the structure: -R"OOC { _C { OOR", where R" is C1-C4 alkyl. This-reaction is generally carried out in the presence of a solvent such as dichloroethane or a C1-C4 alcohol such as methanol, at a temperature between O and 100~C to yield a B-anilino-3 ~,B-unsaturated ester as formula LXIII. The B-anilino-~,B-unsaturated ester of formula LXIII is then reacted with an immonium salt depicted by formula LXIV having the structure:

e e Cl~H--N--( R " ' ) 2 ~ Cl wherein R"' is C1-C6 alkyl or LXIVa having the structure:
e~ e Cl{H N ( CH 2 ) n ~ Cl where n is 4 or 5. While the anion in formulas LXIV or LXlVa is shown as Cl , it should be recognized that when POCl3 is used to prepare the Vilsmeier rea2ent, the anion is P02Cl2. This reaction is generally con-ducted in the presence of a solvent such as methylene chloride, dichloroethane, monochlorobenzene, ortho-dichlorobenzene, or toluene at a tempera~ure between 40and 110~C for a period of time sufficient to complete the reaction and yield the quinoline-2,3-dicarboxylate shown as formula LXVa having the structure:

OOR"
OOR"
' N

(LXVo) wherein L, M, Q, R7 and R" are as described above.
The immonium salt formula LXIV or LXIVa utilized in the above cyclization reactions may, here-after, be referred to as the Vilsmeier reagent. This reagent may be generated from a (N,N-dialkyl or N-alkyl,N-phenyl) formamide reaction with POC13, COCl2, ClCO-COCl or SOCl2 in a hydrocarbon or chlorinated hydrocarbon solvent.

133~3 1 5 Conversion of the 2-methyl-3-quinoline-carboxylate shown as formula LXV in which R'=CH3 to the corresponding aldehyde of formula LXVII can be achieved in a manner similar to that described above for the conversion of the substituted 2-methylnicotinate of formula LIII to the corresponding 2-formylnicotinate of LVIII.
Conversion of the quinoline-2,3-dicarboxylate, shown as formulas LXV and LXVa, to the corresponding aldehyde shown as formula LXVII having the structure:

~ OOR"
R7 ~ \ ~ HO
~ N

(LXVII) where L, M, R7, R8 and R" are as defined above, can be achieved by reaction of the formula LXV quinoline-2,3-dicarboxylate with diisobutylaluminum hydride. The reaction is preferably conducted in the presence of a non-protic solvent such as tetrahydrofuran under a blanket of inert gas.
These reactions are graphically illustrated in Flow Diagram III below.

.

133g31~

FLOW DIAGRAM III
~H2 ~R8 . 5 L ~ R7 +
M

(LXI) R' -CO - CH2COOR" or R"02C - C_C { OOR"
(LXII) (LXVI) Solvent Solvent ~ HfiCOOR" ~ HfiCOOR"
20 R7 ~ N /C R' R7 ~ C - COOR"
H H

(LXIII) (LXIII) 25Cl-CH=N-(R"')2 Cl Cl-CH=N-(R"')2 Cl (LXIV) (LXIV) or or Ci-CH=N~_~(CH2)n Cl ClCH=N~_~(CH2)n Cl (LXIVa) (LXIVa) -31- 133931~

FLOW DIAGRAM III (Continued) (LXIVa) (LXIVa) L ,L
~/~O O R " 1~--CO O R "
R7 ~ N R' R7 ~ OOR"

(LXV) (LXVa) (iBU)2AlH (iBu)2AlH
when R '= COOR "

- ~ OO R "
R7 ~ N HO

(LXVII) 3o 13~931~

The 2-t2-imidazolidinyl)thieno- and furo-[3,2-b]pyridine-6-carb~xylates; 2-(2-imidazolidinyl)-2,3-dihydrothieno- and furo[3,2-b]pyridine-6-carbo-xylates; 2-(2-imidazolidinyl)thieno- and furo[2,3-b]-pyridine-5-carboxylates and 2-(2-imidazolidinyl)-2,3-dihydrothieno- and furo[2,3-b]pyridine-5-carboxylates, useful as intermediates in the preparation of the formula (I) compounds of this invention can be obtained, by reduction of the corresponding (2-imidazolin-2-yl)-thieno- and furo[2,3-b] and [3,2-b]pyridines with sodium cyanoborohydride. These 2-(2-imidazolin-2-yl)-thieno- and furo[2,3-b] and t3,2-b]pyridine inter-mediates, necessary for the preparation of the formula V, VI, VII and VIII, thieno- and furopyridines, of the present invention are described in the copending Canadlan patent application of Marinus Los, David William Ladner and Barrington Cross, Serial 455,718~2 , flled ~June 1, 1984.

The 2-(2-imidazolin-2-yl)thieno and furo-[2,3-b] and t3,2-b]pyridine intermediates, ~sed in the synthesis of the 2-(2-imidazolidinyl)thieno- and fu-~-[2,3-b] and [3,2-b]pyridines starting materials for the compounds of the present invention are depicted by formulas Va, VIa, VIIa and VIIIa, illustrated below.

~ ~ OOR Rll ~ ~ OOR
Rl o N ~Y N--R 2 Rl 2 N /~ N--R 2 H~--W HN~W

(Va ) ( VIa ) 1~39315 Rlo~ ~OOR R12 J~COOR
R9 B N~/ N--R2 11~ B N ~/ --R2 HN =W HN--W

(VIIa) (VIIIa) wherein R is hydro~en or Cl-C4 alkyl and R1, R2, Rg, 1o Rlo, R11, R12, B and W are as described above in reference to compounds of formula V, VI, VII and VIII.
While for convenience, the imidazolinone and imidazolinethione intermediates referred to throughout are illustrated by single structures, it should be 15 recognized that the imidazolinyl function in these compounds may exist in either tautomeric for~, i.e:
H Rl Rl _~ N--R 2 1~ N--R 2 N~--W HN--W

The formula Va, VIa, VIIa and VIIIa, inter-mediates for the compounds of the present invention may be prepared from the appropriately substituted thieno-and furot2,3-b] and [3,2-b]pyridinedicarboxylic acids 25 and esters of formulas LXXI znd LXXIa illustrated below.
Since Rg and R10 represent substituents selected from hydrogen, halogen, Cl-C4 alkyl and phenyl, and R11 and R12 represent hydrogen, Cl-C4 alkyl and - -phenyl; for the purposes of the following discussion, 3~ which relates to the preparation of the formula Va, VIa, VIIa and VIIIa, 2-(2-imidazolin-2-yl)thieno and furo[2,3-b] and [3,2-b]pyridines, compound structures involved in the synthesis under discussion will be illustrated with Rg and R10.

1339~1~

Rlo I ~CCC)2R~ ~ ~CO2;R~

Rg ~ B ~ N CO~R~ and Rlo N C02R
~ ~) whereln Rg, Rlo and B are as prevlously descrlbed and R" ls methyl or ethyl.
Methods sultable for preparing formula Va, VIa, VIIa and VIIIa unsaturated compounds whereln - - ls a double bond from the formula (LXXI) and (LXXIa) pyrldlnedlcarboxyllc acld esters are lllustrated ln Flow Dlagram IV below.
Thus formula (LXXI) and (LXXIa) dlesters may be hydrolyzed to the correspondlng thleno- and furo-2,3-pyrldlne-dlcarboxylic aclds of formula (LXXII) and (LXXIIa) by reactlon thereof wlth a strong base such as potasslum hydroxlde or sodlum hydroxlde. Acld anhydrldes of formula (LXXIII) and (LXXIIIa) may then be prepared by treatment of the formula (LXXII) and (LXXIIa) pyrldinedlcarboxyllc aclds wlth, for ex-ample, acetlc anhydrlde. Reactlon of formula (LXXIII) and (LXXIIIa) anhydrldes wlth an approprlately substltuted amino-carboxamlde or amlnothlocarboxamlde depicted by formula (IX) ylelds carbamoyl nlcotlnlc aclds of formula (LXXIV) and (LXXIVa). Treatment of the thus-formed formula (LXXIV) and (LXXIVa) carbamoyl nlcotlnlc aclds wlth about 2 to 10 molar equlvalents of aqueous or aqueous alcohollc sodlum or potas-slum hydroxlde, preferably under a blanket of lnert gas such as nltrogen, coollng and acldlfylng to pH 2 to 4 wlth a strong mlneral acld such as hydrochlorlc acld or sulfurlc acld glves herblcldally effectlve 6-(4,4-dlsubstltuted-5-oxo-(orthlono)-2-lmldazolln-2-yl)thleno- and furo[2,3-_]pyrldlne-5-carboxyllc aclds, and 5-(4,4-dlsubstltuted-5-oxo(or thlono)-2-lmldazolln-2-yl)thleno- and furo[3,2-_]pyrldlne-6-carboxyllc aclds encompassed by formulas (Va) and (VIIa).

,~

.

~ 133~1s Formula (Va) and (VIIa) 5-(2-imidazolin-2-yl)thieno- and furopyridine esters, wherein R represents a substituent other than hydrogen or a salt-forming cation, and R1, R2, Rg, Rlo and B are as described above can be prepared by reacting a novel thieno- or furoimidazopyrrolopyridinedione, represented by formulas - (LXXV) and (LXXVa), hereinbelow, in Flow Diagram (V), with an appropriate alcohol and correspondin~ alkali metal alkoxide at a temperature ranging between about 20 and about 50~C.
Formula (LXXV) and (LXXVa) thieno- and furo-imidazopyrrolopyridinediones may conveniently be pre-pared from formula (VIIa) and (Va) acids, where R is H
by treatment with one equivalent of dicyclohexylcarbo-diimide in an inert solvent such as methylene chlorideas illustrated in Flow Diagram (V) below.

3o -36- 1339~15 FLOW DIAGRAM (IV) 5 Rlo ~ ~ ~ OOR" ~ ~ OOR"
Rg B N OOR" Rlo OOR"

(LXXI) (LXXIa) l. Aqueous ethanolic NaOH

. 2. HCl Rlo ~ ~ OOH R9 ~ B ~ OOH
Rg OOH Rlo OOH
B N N
20 (LXXII) (LXXIIa) Ac20 R9~ B ~ , Rlo~

(LXXIII) (LXXIIIa) 133931~

FLOW DIAGRAM ( IV) (Continued ) (LXXIII) (LXXIIIa) Rll NH2~--CW--NH2 ( I X ) Rl 0~ ~OOH ~1 ~ ~OOH ~1 9 B N ONH~W--NH2 Rl o N ONH~W--NH2 ( LXX IV ) ( LXX IVa ) NaOH

R~ B ~/ N--R2 R~ I ~/ --R2 N~ W
H

FLOW DIAGRAh~ (V) R~4~N ~ Rlo~ ~OOH R
H N N '~

DCC

R 1 ~ ~ N--=0 1~~N --O
R9 Rlo B N N R2 N r~ R2 Rl R

( LXXV ) ( LXXVa ) R O-M +

Rl~ ~COOR3 Rl : R91~ B ~{c~R3 Rl ~1~ ~</r~ R 2 R 1 o ~ N ~/L< N--W

3o -39- I 339 3I~

where Ml is an alkali metal, and X, Y, Z, Rl, R2 are as above defined and R3 is C1-C4 alkyl.
Many formula (LXXI) thieno[2,3-b]pyridinedi-carboxylic acids and tLXXIa) thieno[3,2-b]pyridinedi-carboxylic acids may conveniently be prepared by reactingthe appropriately substituted 2 or 3-aminothiophene of formula (LXXXIV) or (LXXXIVa) with a C1-C4 alkyl ester of acetylenedicarboxylic acid of formula (IX) as described by Bleckert et al. Chem. Ber. 1978, 106, 368.
The thus-formed ~-aminothieno-~,~-unsaturated ester of formula (LXXXV) or (LXXXVa) is then reacted with an immonium salt depicted by the formula Cl-CH=N-(R''')2 e ~-_ e Cl wherein R''' is Cl-C6 alkyl or Cl-CH=N (CH2)n' Cl where n' is 4 or 5, in the presence of a low boiling chlorinated hydrocarbon solvent such as methylene chloride or dichloroethane at a temperature between about 40 and 90~C, for a period of time sufficient to essentially complete the reaction and yield the formula (LXXI) [2,3-b]thieno- or (LXXIz) [3,2-b]thieno-2,3-pyridinedicarboxylic acid as the dialkyl ester asillustrated in Flow Diagr2m (VI) below.
The furo[3,2-b]pyridinedicarboxylic acids may be prepared by reacting 3-amino-2-formylfur2n of formula (LXXVI) prepared by the method of S. Gronowitz et al., Acta Chemica Scand B29 224(1975) with ethyl oxalacetate to give the furopyridine compounds directly, as illus-trated in Flow Diagram (VII) below while the furo[2,3-b]-pyridine compounds where Rg and Rlo are H are obtained by bromination of the reaction product (LXXVII) of 3o aceto2cet2mide with the diethyl ester of ethoxymethylene-oxal2cetic acid followed by treatment with sodium boro-hydride and para-toluene sulfonic acid in refluxing xylene as illustrated in Flow Diagram (VIII) below.

133~31S

FLOW DIAGRAM (VI) Rlo Rlo NH2 I I or ll I
Rg - S -NH2 Rg ~ /

(LXXXIV) (LXXXIVa) R"02C-C-C-COOR"

(IX) Rlo I I Rlo ~--C - COOR"
{ OOR" or R9 ~ S
HC--COOR "

(LXXXV) (LXXXVa) e Cl{H=N - ( R " ' ) 2 .Cle or Cl-- CH=N ( CH2 ) n ~ . Cl Rlo ~ OOR" R9 ~ ~OOR "
3~ Rg /JL-COOR" Rlo OOR "
S N N

(LXXI) (LXXIa) 13393l~

FLOW DIAGRAM (VI I ) ~ R9~0~CHO

Rl o ' NH2 (LXXVI) C2H502C--lCI--CH2--C~2C2H5 R91~~02C2H5 Rlo02C2H5 3o -42- ' 133931~

FLOW DIAGRAM (VI I I ) CH3 { -CH2 { -NH2 + C2HsO ~-C-CO-C02C2H5 C2HsOH/NaOAc H

CH3 - C ~ 02C2H5 48PHBr/Br2 O CO2C2Hs H
(LXXVII) BrCH2{~C02C2H5 NaBH4 ~ ~ ~ ~2C2H5 H
O,H
BrCH2--CH--~co2c2H5 l 11 (C2H5)3N
20~ ~ N ~ C~2C2H5 H

OH
25~ 02C2H5 p-Toluenesulfonic acid ~02C2H5 ~ 2C2H5 O N
3o Substituents represented by Rg and Rlo in formula (Va), (VIIa), (LXXV) and (LXXVa) compounds of the present invention may be prepared either by using the appropriately substituted starting material for the preparation of formula (LXXI) and (LXXIa) thieno- and furopyridine-5,6-dicarboxylic acid esters or by electro-philic substitution (halo~enation, nitr2tion, sulfon2-tion, etc.) directly upon formula (LXXI) or (LXXI2) diesters or Formula (Va) or (VIIa) final products, wherein at least one of Y or Z is hydro~en. These substituted formula (LXXI), (LXXIa), (Va) and (VIIa) compounds then may be used as startin~ m2teri21s for additional Rg and Rlo substitution by dlsplacement, reduction, oxidation, etc. Representative substituted (LXXI) and (LXXIa) compounds which m2y be prep2red by these procedures are as illustrated below.

Rlo~ ~C 02R R91~ ~~2R
Rg B - N o2R Rlo 02R

(LXXI) (LXXIa) _ Rg Rlo R

S H Br CH3 S H Cl CH3 S Cl Cl CH3 S H No2 CH3 S Br Br CH3 13~931~

B Rg R10 R
S CH3 Cl CH3 S Cl H CH3 S H N(CH3)2 CH3 S H OCr2H CH3 O H Br CH3 O H Cl CH3 o CH3 H CH3 ~ CH3 H C2H5 o CH3 CH3 CH3 S -(CH2)3- CH3 S -tCH2)4- CH3 S -(CH)4- CH3 ~CH3 ~ CF3 H CH3 '~ 1339~1~
Additionally, novel herbicidal 2,3-dihydro-thieno[2,3-b] and [3,2-b]pyridine compounds may be obtained by starting the sequence in Flow Diagram (VI) above with a dihydrothiophenimine hydrochloride. Novel herbicidal 2,3-dihydro furo[2,3-b] and [3,2-b]pyridines may be prepared by catalytic reduction of the formula (Va) or (VIIa) (2-imidazolin-2-yl) product, or (LXXI) - and (LXXIa) furo[2,3-b] and [3,2-b]pyridine-5,6-diesters as for example with hydrogen and palladium on carbon, provided that Rg and Rlo are substituents which are not reduced by such a procedure. This then provides novel 2,3-dihydro herbicidal compounds illustrated below.

R9 ~ <N R2 Rl~ ~ \/N R2 B N N~W N N--W
H H

wherein Rg, Rlo, B, W, Rl, R2 and RB are as described for (Va) and (VIIA).
The formula I dihydroimidazopyrrolopyridines and derivatives of the present invention are highly effective preemergence and postemergence herbicidal agents, useful for the control of a wide variety of undesirable monocotyledonous and dicotyledonous plant species. Surprisingly, it has also been found that these formula I compounds are very active against a wide variety of weed species but well tolerated by a - number of crops including: graminaceous crops such as sunflower, corn, rice, turf, and wheat; leguminous crops such as soybeans and other crops including cotton.

133931~

While herbicidal selectivity of the formula I compounds of this invention may vary with compound structure from crop to crop, the presence of the dihydroimidazopyrrolo-pyridine function, which is unique to all of the formula I compounds of this invention, appears to impart signi-ficant herbicidal selectivity to said compounds. This selectivity thus permits application of the active compounds to newly planted fields or to maturing crops for control of undesirable grasses and broadleaf weeds 0 in the presence of said crops.
It is also surprising to find that the com-pounds of this invention, frequently exhibit plant growth regulating activity when employed at non-herbicidal rates of application.
In practice, the formula I dihydroimidazo-pyrrolopyridines and derivatives thereof may be applied to the foliage of undesirable monocotyledonous or dicotyledonous plants or to soil containing seeds or other propagating organs of said plants such as tubers, rhizomes or stolons, at ranges generally between about 0.032 and 4.0 kg/ha, and preferably between about 0.063 and 2.0 kg/ha, although rates as high as 8.0 kg/ha may be used if desired.
Effective plant growth regulating activity such as dwarfing, antilodging, increased branching, increased tillering and the like, is generally obtained when the above-said formula I compounds are applied to crops at rates below herbicidal rates. Obviously, this rate will vary from compound to compound.
The formula I compounds of the present inven-tion may be applied to the foliage of plants or to soil containing seeds or other propagating organs thereof, in the form of a liquid spray, as a ULV concentrate or as a solid formulat-on.

1339~1~

Formula I compounds may also be prepared as wettable powders, flowable concentrates, emulsifiable concentrates, granular formulations or the like.
A typical emulsifiable concentrate can be - 5 prepared by dissolving about 5 to 25% by weight of the active ingredient in about 65 to 90p by weight of N-methylpyrrolidone, isophorone, butyl cellosolve, methylacetate or the like and dispersing therein about 5 to 1 Od by weight of a nonionic surfactant such as an alkylphenoxy polyethoxy alcohol. This concentrate is dispersed in water for application as a liquid spray or it may be applied directly as an ultra low volume con-centrate in the form of discrete droplets havin& a mass median diameter between about 17 and 150 microns particle size.
Wettable powders can be prepared by grindin&
together about 20 to 45p by weight of a finely divided carrier such as kaolin, bentonite, diatomaceous earth, attapulgite, or the like, 45 to 80p by weight of the active compound, 2 to 5p by weight of a dispersing agent such as sodium lignosulfonate, and 2 to 5% by weight of a nonionic surfactant, such~ as octylphenoxy polyethoxy ethanol, nonylphenoxy polyethoxy ethanol or the like.
A typical flowable liquid can be prepared by admixing about 40% by weight of the active 1ngredient with about 2% by weight of a gelling agent such as bentonite, 3~ by weight of a dispersing agent such as sodium lignosulfonate, 1% by weight of polyethylene 3~ glycol and 54~ by weight of water.

-' 1339315 When the compounds of the invention are to be used as herbicides where soil treatments are involved, the compounds may be prepared and applied as granular products. Preparation of the granular product can be achieved by dissolving the active compound in a solvent such as methylene chloride, N-methylpyrrolidone or the like and spraying the thus-prepared solution on a granular carrier such as corncob grits, sand, attapul-gite, kaolin or the like.
The granular product thus-prepared generally comprises about 3 to 20% by weight of the active ingre-dient and about 97 to 80% by weight of the granulzr carrier.
In order to facilitate a further under-standing of the invention, the following examples are presented primarily for the purpose of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. Unless otherwise noted, all parts are by weight.

49 133931~

Preparation of 7-ethyl-1,9b~(and ~)-dihydro-3~-isopro-pyl-3-methyl-5~-imidazo~1',2':1,2]pyrrolo~3,4-b~pyridine-2(3H)~5-dione H5 C2~\~~ O H

~, N---CH(CH3 )2 lN
HN--O

HsC2 ~ N CH(CH3)2 (CH3C0)2o ¦ ~1 O
N ' N

A suspension of 1 g of cis- and trans-5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-nicotinic acid and 0.4 mL pyridine and 0.5 mL acetic anhydride in 10 mL acetonitrile is warmed to about 50~C until a clear solution is obtained. Upon cooling the solution to room temperature, a solid crystallizes. The solid is collected by filtration and recrystallized from ethyl acetate to give analytically pure 7-ethyl-1,9b ~(and ~)-dihydro-3~-isopropyl-3-methyl-5H-imidazo[1',-2':1,2]pyrrolo[3,4-b]pyridine-2(3H),5-dione, mp 170-177~C.

3o -50- ~' 13393~5 Preparation of 7-dimethyl-1,9bB-dihydro-3~-isopropyl-3,5H-imidazo[1',2':1,2]pyrrolo[3,4-~]pyridine-2(3H),-5-dione CH3 ~ 00H
~JIIII H NH CH3 + ~N=C N~
CH(CH3)2 HN ----~

CH3 ~ 1I CH(CH3)2 ~cO
N . N
~ H

A mixture containing 1.08 g of cis-2-(4-iso-propyl-4-methyl-5-oxo-2-imidazolidinyl)-5-methyl-nicotinic acid and 0.89 g of N,N'-dicyclohexylcarbodiimide in 25 mL methylene chloride is stirred at room temperature for 18 hours. The mixture is filtered and concentrated in vacuo. The crystalline residue is recrystallized from methylene chloride to give analytically pure 7-dimethyl-1,9bB-dihydro-3~--sopropyl-3,5H-imidazo[1',2':
1,2]pyrrolo[3,4-b]pyridine-2(3H),5-dione, mp 1~1-193~C.

3o 133931~

Preparation of 1,9b~(and ~)-dihydro-3~-isopropyl-3-methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-2-(3H),5-dione CH(CH3)2 + NaBH4 ~=0 N N

/~ N CH ( CH 3 ) 2 1 5 ,L O
N ' N
~ H

To a suspension of 1.7 g sodium borohydride in 120 mL absolute ethanol cooled to 0~C is added drop-wise a solution of 10.8 g 3-isopropyl-3-methyl-5H-i.~idazo-[1',2':1,2]pyrrolo[3,4-b]pyridine-2(3H),5-dione in 120 mL dry tetrahydrofur2n, maintaining the temperature between 0 and 5~C. The mixture is stirred at room temperature for two hours and added to ice water. The aqueous mixture is acidified to pH 3 with concentrated sulfuric acid and extracted with methylene chloride.
Extracts are dried and concentrated in vacuo to give a solid. The solid is washed with anhydrous ether and air dried to give 1,9b~(and ~)-dihydro-3~-isopropyl-3-3~ methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-2(3H),-5-dione, mp 170~C (dec).

133931~

Preparation of formula (I) dihydroimidazopyrrolo?yridines or derivatives thereof Following one of the procedures described in Examples 1, 2 or 3, the compounds of formula (I), reported in Table I below, were prepared.

3o o. o. o. u~ o.
~) O u a~ o C~, 6~ , ~1,,,, C~ O ~ O ~D C~
~ ~ o o o --ZI

X~ ~Z U ~ C~ ~ ~ ~ ~
r~
U~
cn C 3 1 0 0 ~ ~ ~ ~

-cn ,_, U
r ._ r ~L ZI

x~\ z u ~f G

U

~a ._ O
L~

oooooooooooo o C~ ~ ~ ~ C
~ 1 ~ , , , , , , , , , , , EiIoooooooooooo U~ ~ o ~ ~ o o ~ ~ ~ ~ '~
~ o o C~ ~ ~ o C~1 C ~ ,,~, u~l ._, I ~ o ~ ~ ~ ~ ~ ~

31 0 0 0 o o o o u~ o o 0~
. ~ ~ T C ~n~ T
.C C~l ~
C C~ T

X ¦ T T T T T 5~ T C T T' ~ ~

~ T

~ v ~, t~ e~ ~ ~ ~ ~ ~ ~ c~ ~
CY: I

~1 13~31~

o o o o o o U~ o o o o .

oooooo~o o o o c~J o o c~ c~ ~r ~ ~-- ~ o o ~ ~ ~ ~) o a~ ~ ~ ~ u~
cn C ~ ~D
J

Cl~ I

- 31 o U~ o o o o o c~ o o o C~ I ~ ~ ~ T ,C T = ~ ~ ~3 Z

-- ~ -- C~ ~ C T
T

X ¦ ~ T T -- ~ T T T

T ~ ~ r T

C~l ¦ ~ T ~

~l ~_ ~ ~ ~

Preparation of3-isopropyl-3-methyl-5H-imidazo[1',2':1,2]-pyrrolo[3,4-b]pyridine-2(3~),5-dione ~COOH

N/~ CH(CH3)2 H~ --O

AcOH
.AC20 ~ ~ CH(CH3)2 N N

A stirred mixture of 123.2 g acid in 300 mL
acetic acid and 89 mL acetic anhydride is heated at reflux for four hours. The mixture is concentrated in vacuo and the residue dissolved in toluene and again concentrated. The residue is slurried in hexane, fil-tered and washed several times with hexane to give a 90% of product, mp 105-112~C. NMR and Gc analysis indicztes this material to consist of 80-87% of the desired 2,5-dione and the balance of the material being the corresponding 3,5-dione.

~57~ ~ 1 3~9 3 Preparation of 1,9b-dihydro-3~-isopropyl-3-methyl-9b~-propoxy-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-2-(3H),5-dione N N

~ ~ ~

N - N
n-C3H70 H

The solution containing 54 g dione in 200 mL
n-propanol is heated at reflux for one hour. The solu-tion is slowly cooled to 0~C and after one hour, the white crystals removed by filtration. The solids are washed with hexane and dried to give 41.6 of the 9b~-25 propoxy derivative mp 129-132~C. This material can be recrystallized from ether-hexane to give analytically pure material mp 135-137.5~C. This product can also be obtained by running the reaction at room temperature.
Using essentially the same conditions but 30 utilizing the appropriate nucliophile and the appro-priate 2,5-dione, the following dihydro derivatives are prepared.

1339~1~

CCCCC

~) o o U~

N ¦ T T S T T

~ ¦ T -r T X ~ T

X~Z ~ C 111 1, . ~ o o o ~

~C~ ~ C~
.. ~C~

1339~15 ~ ~ CC C C
s~~_1 Ll LLl O

N

C~ ~

X IT' ~C~ ~ ~ -- T' --I

) v v ~ o o I

3 1 0 0 0 0 0 U~ O C~

V V ~ V V V C~
V ~

V ~

133~15 Preparatlon of methyl 2-(4-lsopropyl-4-methyl-5-oxo-2-lmldazolln-yl)nlcotlnate Thls method lnvolves the formatlon of trycycllc com-pounds, wlthout lsolatlon, dlrectly formlng the nlcotlnlc acld esters:
o ~ N-C-~30NH2 DBU > ~ R2 N ~ CH~CH3~ N N

CH3 MdDH

HN~ ==O
~H3 N CH~CH

~ N
COO~I3 A mlxture of 25 g amlde and 1 mL 1,5-dlazablcyclo-[5.4.0]undec-5-ene(DBU) ln 500 mL xylene ls heated under re-flux for one hour under a Dean-Stark water separator. The mlxture ls cooled somewhat, the water separator removed, 100 mL anhydrous methanol added and the mixture heated under re-flux for one hour. The solvents are then removed ln vacuo and the product lsolated by chromatography as to glve 13.65 g pro-duct mp 120-122~C. Other esters as descrlbed ln Example 28 in the same manner uslng the approprlately substltuted amlde startlng materlal. Thls procedure ls also descrlbed ln the Canadlan Patent 1,187,498 whlch lssued on May 21, 1987 on Marlnus Los.

-~r 61 1339~1S

Preparatlon of methyl 2-(4-isopropyl-4-methyl-5-oxo-2-lmidazolin-2-yl)nicotlnate CCKX~H3lH3 ~ CCXX~CHH
N CONH - I-CONH2 ~N ~ - CH(CH
CH(CH3~ HN - ~

Method A
A mlxture of 13.65 g of the nlcotlnate and 9.69 g phosphorus pentachloride in 110 mL dry toluene is heated with stlrrlng to 80~C. After one and one-half hours, the thlck mlxture ls cooled, filtered and the solid washed with ether and dried. This is the hydrochlorlde salt of the deslred product.
This salt is dissolved in 60 mL water; neutralized with sodium bicarbonate, the resulting preclpitate removed by flltration, washed wlth water and air-drled to glve the product.
Method B
A mlxture of 5.0 g nlcotlnate and 7.1 g phosphorus pentachlorlde ln 40 mL phosphorus oxychlorlde is stirred at room temperature overnlght. THe phosphorous oxychloride is removed ln vacuo, the residue suspended in 40 mL toluene and again concentrated. This is repeated. Water (40 mL) is added to the residue and the mlxture heated to reflux and held there for one hour. After cooling, the mixture is extracted wlth methylene chlorlde, the extract dried and concentrated to glve 1.05 g of the deslred product. The pH of the aqueous phase from the methylene chlorlde extraction is ad~usted to 5-6 wlth sodlum blcarbonate solutlon and the mlxture extracted agaln wlth methylene chlorlde. The drled extract was concentrated and the residue crystallized to give a further 2.65 g of the desired product.

The following nicotinic acid esters are prepared by one or more of the methods described above:

Y~OOR

N ~/ N--R 2 Hr~ - O

1339~15 u~ o ~ o ~n o o o o o O ~ ~ o _ o o lr~ ~ In 3 ~
0~
m o o o Ln o -o o o o ~ o m ~ 3 C~ ¦ T ~ T ~ T

~ ¦ T ,1_ T T -- T ~ C

X I ~ _ T -- _ T ~ X T

--_ T -- -- t~l ~ 3 T T T

~ 3 T T

._ ¦ ~ T ~ ~ _ T U~

T T T T T T -- I .~.

133~

o o o o o Lr~ ~ o o .. ~ .Ln ~ ~ o ~ L~ ~ ~ ~ ~I t~) 3 0 O ~ ~ a~ o 0 ~
E O O
O oo ~ o O o O O
U~~ O 0 3 t~J O '- 0 t~J ¦ T =:C T :C T ~ T -- T ~

~-4 ¦ T = _~ T ~ = ~ T

X ¦ _ = = T . S T = -- _ ~ ---- _ T ~ T ~ 2 c~
_ _ -- ~ -- -- _ _ --I ~ ~ C ~ ~ ~ T 'r ~ S' CC C.) -- ~) L
~r ~ ~r o ~

~ O -- /t~l ~ 111 0 C_) 11 C) t~

o o ,- o o o o o o ~ U~ o o o ~ ~ C~ ~ ~ L~
C ~
O O O ~) Ln O O O Lt~ O O O

t~¦ -- T X C T -- T T T S T -- O

¦ _ ~ ~ T 3 = ~ ~ T ~ T

X I -- T _ _~. T ~ ,T T T ~ T

~ ~J ~ N ~J~ T ~ ~
T -- ~ ~ T -- T C_) T-- T T T T 3 ~ y --~__ T T ~ T~ _3~ ~ ~ ~ ~ ~

T I~_ I~ :C ~' T ~
,~ rt~l r--T ~ C ) T
T
y y ~ T y ~ t_ C ~ T

' ~ 1339315 o o o o o U~ o o L~
~ ~ ~ 0 ~ o OQ ~I ~ ~ I I I ~ I I I I I
F O O O bl~
O O L~ O Lr~ O O L~ O O Lt~ O
3 0 L~ J 3 ~ 3 3 3 r~ D ~) O ~

¦ T ~ -- T -- X ~ ~ T T ~ ~ , I ~ =

~ ¦-- T T a T ~ T ~ X ~ T

X ¦ , = _ _ T ~ = ~ ~ ~ _ T -- -- --~ 2 T ~ ~ ~1 (~I I 3 ~ -- :C T ~J T -- ~ T

T T

.--1 ~ T T T ~ T (~J T ~ ~ ~ ~ ~--~ I ~ (D
C-- ~ T o~ ~

T In ~_) 2 t~J T T

T T T T T T _~ _ T ~

133931~

o o o o o o o ~~ CO ~ ~8 ~ ~ ~ ~ o ~ ~
o ~ ._._ E O OO
~n o o u~ o o O ~ ~

c T T _ ~ ~ ~S' C

T ~ I T I = _ T~: I

X¦ I T I I I T -- = =

-- -- I ~ _T
T ~
N~ I T _ -- ~ ~I = I

--I - ~ I T X I I IT T

(~ ~ ~ o o _ 8 T ~? C b~ ~~ -T ~ ~ -- C TT C_) 13393l 5 o o o o O
~ o ~ ~ ,~, o Q l l l l O O
O O O O O
~) ~ O ~i t~i O O

T ~, ~ T

-r T

X I-L. 3 C_) ~ _ =~r ~_1 ~ 2 I: T-- T ~

¢

-69- 133931~

o o Lr~
3 Ln 3 O _ _ _ _ _ E~ O O O O O
O O O

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~1 ¦ ~ I ~ T T ~ T T

X ¦ T T :C -- T , _ _ T -- _ _ -- T _ T ~ I I r 3 ~ 3 T -- T

~ 8~, ~, T

T '~O ~ --' ~ \~ 111 U C ) C~
T ~ ~_~ T

- - 13393~

Ln o o o o 0 o CO o ~ U~ U~ o ~ o ~ ~~ ~ ~ ~ o ~
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Lr O O L~ O ~n 11 o It o 11 u~ o o . a . a. a.
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T --~ T -- ~ Z _ _ ~ ¦ T T T T T

X I = T TT -- _ ~ ~r _ T

_ _ __ _ _ _ _ _ _ _ T --_ -- -- -- T ~ ~ =
~J ¦ T = -- ~r ---- 1:: =T T T ~r ~-- --U~
T ~.0 ' ' I
~: o~ 5 ~ T T ,_~

-71- 133~31~

o o o o o o U~
~ U~ ~ ~ ~ o ~ ~) O ~ ~ N 3 ~ ~ o a~
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o o o ~ o O O O O
cr) ~ O ~OO In 3 U~ ~

Y
~D ~ I C~
~lo~ ~ ~

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~ o U~ o o o o 0 3 0 a' ~ t~i ~i 0 ~ ~ ~ U:~ ~ . - ~ 3 O ' L~ O O O Ln O O O
~o o cr~ O
o ~-- ~ ~ a~

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.
T T
C~ ~ C,) T ~ ~ ~

133931~

Preparation of cis- and trans-methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate I NaCNBH3 CH2=CHCH20 N ~/ N - CH(CH3)2 HN---~~=O

~ OOCH3 CH2=CHCH20 ~ \ ~ ~ H CH3 +

HN - = O

~ OOCH3 CH2=CHCH2 O ~ \N ~ N CH(CH3)2 HN - O

A solution containing 7.0 g (22.1 mmol) methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate in 70 mL absolute methanol is cooled to 0~C and a few drops of methyl orange indicator added. To the stirred solution is added 1.8 mL (22.1 mmol) concentrated HCl. The red solution is warmed to room temperature and 1.4 g (22.1 mol) sodium cyanoborohydride is added. Slowly, the solution turns to an orange color (pH ~4) and 2N methanolic HCl is added to the mixture until a red tint is observed (pH -3). This procedure of pH adjustment is repeated 133931~

until there is no longer a change. After stirring overnight at room temperature, the solution is cooled to 0~C, the pH adjusted to ~0 with concentrated HCl to decompose residual NaCNBH3. The pH is then adjusted to 5-6 with 5 N NaOH. The methanol is removed in vacuo and enough water added to the residue to dissolve inorganic salts. This mixture is thoroughly extracted with CH2Cl2, the extracts dried and concentrated. The residue (~7.8 g) is a thick oil which is chromatographed on 350 g silica gel. Using 1:1 CH2Cl2-hexane followed by ether as eluants results in the separation of 0.35 g starting material. Further elution with ether results in the isolation of 1.87 g of the trans-isomer, and further elution with 10~ methanol in ether gives 5.2 g of the cis-isomer.
The trans-isomer is recrystallized from CH2Cl2-hexanes to give 1.16 g of analytically pure trans-methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate, mp 144-142~C.
Similarly the cis-isomer is recrystallized from CH2Cl2-hexane to give 4.6 g analytically pure cis-methyl 6-(alloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate, mp 120-122~C.
Using essentially the same procedure but substituting the appropriate 5-oxo- or 5-thioxo-imidazo-linyl nicotinate for methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate, gives the following 5-oxo- and 5-thioxoimidazolidinyl nicotinates.
Other compounds that can be prepared by the above procedure are described in Table III below.

_75_ 133931~

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C' G E
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~ ~ E C _ C

¦ = -- T

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C~
o ~ / ~ 31 o O O
c ~o Z

X--<~\ /z ~ I
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C~

T
IX t~

lll -76- ~ 133 9 3 1~

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t; C' E
CJ L~
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O ~ O O O O O
.
--I O ~ ~ O _ O O
~ ~ ~ ~ ~ ~ = ~ J
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t' J~ Q o L~ o o o o o t~ O E
~ 0 ~ 0 ~ 0 0 ._ .~ ~- J ~ J =
E '- ~ ~ ~ ~ ~ ~
H

~1 5 5 55555 ~;
--g ~1 5 5 5555 _ H
H
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m xl = 5 55 -555 C
~' J J
_ ~ ~ ~ ~ = 5 I
55 =
Y~ Y~
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t~ . o t-~ ~ ~ oo o o o G ~ . .. . .
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a ~) Y \~j/ c c c ' ,_ x I ~ ~ :~
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. ,~ _ _ . .
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t' ~' O

8 Q Lr O O O U~ O O O O O O
O O O~ O ~ G~
E ~: O ~ t~ ~O a~ ~ a' ~ --H

t--C.) _ ~) -- T

O

H '-41 S c_) _ _ = _ _ T
X I S S S S S S S S S S

~ s ~ s ~ ~ s s s S T S ~ _ S S T S _ _ S S :~ S S S S S S ~ S

. .
-S
S ~O
S S S S -- ~ ~ S~ ~ S~
-- C~

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~ ~5 o o o ~~ a, C ~ Oo o o .
o E c ~ ,_ ~ 0 l l l t~ L~ o o o C~ o CO o ~ o o o o - ~ o ~ ~~
o ~7 o C~i oo ~ ~ ~ ~ ._ o C C~ I + I +
C ~ ~U~ 11 o 11 o 11 Lr~ o O o o O O
.~ o ~ O ~ ~ a E c ,~
C~

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a .C
c ~ ~ ~ s _, ~
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T ~ T

~n Ln ~~l ~) z ~

~ 1339~
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O O U~
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c xl C

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o o o C ~ .

. ~
C~ o L~ o C . o r ~ c ~
tl O E 3 ~ ~n E C
H U~
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C~' ~O

~ .--O O O O ~ O L~
~O ~ ~ . .
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~3 ooa:~ ~ ~ ~ ~ o ._ ~
IIIIII+
C ~-- O
c~ ~ Q ln o o u~ o O I I O O
~ O E ~ ~ ~ . ~ ~ 2 ~ ~ o ~ u~
._ ._, o ~a:) ~ o ~ ~ o E . ~ ~ ~ ~ ., ~ ~
H

~ s = s s I ~ ~
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._ O ~I s--ss== s~
H
H
H

X I S S S S S S S S
E-3 1 0 0 0 0 0 o u~ v~

s .~ s s s s s s C~l S T S S S ~ S

~ s s s s s s s s L~
~ s c: s c~ s c~ 8 ~ 8 S -- S S S S S S

-82- 13~31S
V~

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t~ O E
.C .C) H
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O O O
O o ~U~ O
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E t- o Cfr~
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aJ , .~
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H

t~ T
m x I T ~_) -- _ T

~ _ _ _ _ _ T ~ T ~r r ~

Y~

' 133931~

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C . o ~ ~ a t~ C E
._ _ F C o~
~1 -1 C~

C ~- O O OO O O
~ ~ a tl O E
H

C~l ¦ T T
-C
-C >'~ ¦ , T , = _ H
H

~ X I T T = T
C

N ~ t~ J N
T TT ~ T
_ _ T T

T T -- T T

t~ T

~/> 8 ~, ~, T

T ~ G~
~O ~ _ T

-84- 133931~

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_ ._ ~ U~ I
cl ~ ~. ~. ~. o o o ~ ~ o C-- .L.~ ~ ~ ~ ~ C~ ~ ~
O ~--O O
C'~ ~ C~ o o U~ o o o Ln 8 E ~ ~D ~ ~ u~ ~ ~
~ ~ o C~
H

C~l ¦ T T T _ T _ T
a --~ ~1 -- ~ ~ ~ = = ~ m H

m X ¦ ~ _ T = T
C

~ -- T T ~ -- T
_ ~ T _ T -- S T

8 ~ ~, u ~ ~ ~ ~ T T T

-85- ' 133931~i o -o .
C C~
C . ,o C' ~ CL o ~ O E
._ ._, cr~
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C~ O
a~
O o o ~ o ~ O
~ a, ~ ~ cr~ ~ O
r ~ _ ~ _ C ~--O O O OO
C O O O ~ O o tt O E
._ ._, o ~ ~ ~ O

_~ T T 5 T ~: S -- --c ._ C
O C~
S ~ ~ ~ T -- T _ ~ O
H
H
H

C~
C X ¦T _ ~ ~ T ~ T ~

TS T T :C ' -- ~ S _ ~ Ll~ S U~ T

T-- T ~ S ~ S S, ~1 ' -- " '' '-' '-' :c ~ T
O S~) ~ C~
~ C. I 11 11 t~
S~ I ,_ :~
~)~' ~ ~) C ~
Il. ~\~ _. I ~ 11 S
-- ~ ~ S
S ~ ~ S' ~ 133931~

o o C
C L O
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O O o ~ o o ~ ~ O o O
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r ~ ~ ~ . .
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C ~-~ O bO
~; ~ Q L~-\ O O L~ O O L~ O O O O
~ O E
C C~ 3 ~~ ~ 3 ~ ~ _ u~ 3 0 E ~~ . ~ . _ . ~ ~ . . ~ .
H

C~ I = S S :~ S ~ S = = S
~ , .~ S
J~
C ~ I ~ _ S

H
H
H

C X I S T = ~ = T S S C~ -- T

~ S TT ~ S ~
~ S~ T,~/-- T t~J ~ --I ', _ S ~J S T ~S C -- ~ T -~

H
S :~
S S
O
Z
I I I C~ S ~ S
T S -- S T ~ S c~

-87- 13393I~
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o o o o o o ~ ~ Ln o o C ~--O O
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t~ O E
E '--C~l ¦ T ~ = r ~ =

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H
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C X I T ~:C ~ -- T ~r -- = -- =
E-T ~ ~ T .,_ _, T
T T ~ -- T T ~ ~7 _ -- ~ T T T -- T

A
C L~
r) ~.D T 7~ 111 ~) C_) \
C I y c~ ~ T T

-88- 133931~

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t~ O E ~ ~ O u~ o o o o C~ ~ _ ~ o ~ ¦ ~ T ~ T'~

-O ~ ¦ T 3 ~ = _ _ T --H

C XI ~ _ ~ _ _ _ _ _ _ T ~ ~
_ _ _ ~ _ ~ _ _ _ ~m 15 C: O

ooooo ~ 1339315 C~ I,III
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1339~1~
-so-Preparation of cls- and tr2~s-5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinic acid C2H5 ~COOH C2H5~COOH
CH3 NaCNBH~ ~ I H H CH3 N--~/ N--CH(CH3)2 N--~N--CH(CH3)2 HN~O HN~O

To a stirred slurry of 2.89 g 5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid in 20 mL methanol and one equivalent of 2N methanolic HCl is added under nitrogen o.6 g sodium cyanoboro-hydride. Methanolic HCl is added to maintain a pH of 2-3. After stirring the pH of the mixture is adjusted to 1 with concentrated HCl and after 15 minutes, agzin adjusted to 3 with saturated NaHC03 solution. After filtration, the solution is extracted with ethyl acetate.
The pH of the aqueous phase is again adjusted to 3 and again extracted with ethyl acetate. A crystalline precipitate of cis- and trans-5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate is formed which can be recrystallized from ethanol to give the product as a white crystalline solid mp 208-210~C. This contains about 66% of the cis- and 34p of the trzns-iscmer.

3~

'~' 1339~1~

Preparation of cis-6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidynyl)nicotinic acid ~ OOCH3 CH2=CHCH20 ~ \N ~ N\---cH(cH3)2 HN - O

~ OOH

CH2=CHCH20 ~ \N ~ N~--cH(cH3)2 HN - O

To a solution containing 3.9 g (12.2 mmol) cis-methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate in a minimum absolute methanol (~15 mL) is added 12.2 mL 2N NaOH solution. A
precipitate results and the mixture is heated with stirring to 45~C and maintained at that temperature for one hour. The solution becomes clear. It is cooled to 0~C and 12.2 mL 2N HCl added. A solid precipitates which is collected, washed with ether and air dried.
This material (3.2 g) is recrystallized from methylene chloride-hexane to give 2.3 g analytically pure cis-6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazo-lidinyl)nicotinic acid, mp 193-194~C.

By using essentially the same procedure, but substituting the appropriate methyl 5-oxo or thioxo-imidazolinyl nicotinate or quinoline-3-carboxylate for cis-methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-. 5 2-imidazolinyl)nicotinate, the following 5-oxo or 5-thioxoimidazolidinyl nicotinic, or quinoline-3-carboxylic acids are prepared. The reaction can be illustrated as follows using nicotinates as represen-tative of the reaction.

Y~COOR Y~COOH
Z~ N R l 3 . z~ H ~1 HN~--W HN eW

93 ' 133931S

, ~.
C~ l C ~ 01 '~1 C cnl u~ I C
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~, ~oooo~ooooooooo o ~ 'J _ ~ ~ o o~ ~ _ ~ C~i ~J
~ o oo r~ a~ o~ o c~ ~ O ~ ~ ~ C~

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~) t~) 2 ~ 2 ~ I ~ ~ 222222211 X 122222 ~ ~ 2222222 3100000000 ~ 00000 ~ SJ
0 ~ 0 ~ 0 0 0 01 @ X @ ~ ~1 X @ 01 01 @ ~01 @
x o~oooo~ooooooo o ~ _ ~ co n ~ ~ o ~ ~ u~ ~ ~
O _' ~D O ~ ~ ~ ~ ~ o ~ c~ ,_ I I I I I
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~ T' 111 111 ~ O O O

X ¦ ~ C ~ ~ ~ T ~ T' 3 1 0 o o o V~ o o o o o o o o _95_ 13393 c c U, u' O~ ~n ~,~ ._, ~,.
~ C~ t~ t~
C~ .
o~ o o o o o .,.U~ C~i ~ o Y~o ~ ;~ o I I I I I
o o o ~ o ~ U~ o C'l Z ~ T' ~ C~l F~
~ I ~ O o X I ~ ~ S ~ ~ ~

1339~15 Preparation of cis-methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate hydrochloride H H CH3 CH~OH
N ~ N ~--CH(CH3)2 HCl HN - O

N ~ N ~ --CH(CH3)2 HN _ O

To 2.0 g cis-methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate is added 25 mL of 2N
methanolic HCl. The solvent is removed in V2CUO and the residue is crystallized from ethyl acetate-ether to give the hydroch-loride salt, mp t89-192~C. Other acid addition salts may be prepared by the above procedure using the appropriately substituted formula III 2-(2-imidazolidinyl)nicotinate.

3o _97_ 133931~

Preparation of sodium 5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate C2H5~COOH
H CH3 NcOH
N N ~ --CH(CH3)2 MeOH

HN - O

C2 Hs~{OOe ~ ~ N CH3 HN - O

To 1.0 g 5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nlcotinic acid is added a solution of 0.1498 g sodium hydroxide in 20 mL absolute methanol. The mixture is stirred under nitrogen at room temperature overnight. The solvent is removed to give a solid which is dried in a vacuum oven at 60~C
for two days. The thus-formed sodium 5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate darkens at 230~C and decomposes at 247-250~C.

Preparation of cis-methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate ~OOCH3 + NH2 f - fONH2 pTSA
HO CH(CH3)2 1 O ~COOCH3 ~, N fH3 HN --O

A solution containing 1.24 g methyl 2-formyl-pyridine-3-carboxylate (Bull. Soc. Chem. France, 36, 78-83 (1969)], 1.0 g 2-amino-2,3-dimethylbutyramide and 20 g ~-toluene sulfonic acid is heated under reflux under nitrogen with a Dean-Stark water sepzrator for six hours. The solution is filtered while hot and the filtrate concentrated in vacuo to leave a dark oil.
The oil is extracted into ether, the ether concentrated to give a yellow solid. This solid is recrystallized from a mixture of hexane-ether and methylene chloride to give cis-methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)nicotinate, mp 118.5-120~C, identical to one of the products obtained from the sodium cyanoboro-hydride reduction of methyl 2-(4-isopropyl-4-methyl-5-oxo-imidazolin-2-yl)nicotinate. The presence of the 3~ corresponding trans-isomer is indicated by nmr spectro-scopy. Following the above procedure and using the appropriately substituted 2-formylpyridine-3-carboxylate yields the formula III 2-(2-imidazolidinyl)nicotinic acids and esters reported in Table IV below.

. i . . .. .
C) C~ C~ ~ C) o o Lr~ o o o a~

E
L~ o o o O
O ~ o ~ 1~l ~; O ~ --, _ T
.~ ~\
~ X--~_fZ

o ~_ C
~ X¦ ~ T T
-o m .~ ~
c E y t~l _ ~ ~ -- -- T

H ~ -- T
H
-E
O O
C~ y y ~ I ~) ~ ~
0 /~\
~" X--~Z

.

u~ o G T ~
~r3: I ~ T

., ., ., ., ., _ .~ _ o o oLr~ooooo - ~ ~ ~ ~ ~ o ~ ~ o ~
V ~ E ~J ~ ~ '~ ~ ~ ~ '~
O O
E ~~ ~
Ln o OOOOOOO

1 1~
~ 5 ~
c~; 5 5 s 5 t~ 5 0 C.) c~ ----r 5 ~ 5 t~ --5 C ) ) -- O -- 5 ~) ~ x I -- 5 5 _ 5 5 -- 5 --J~
o -_ _________ -- ~ -- 5 -- -- 5 -- -- 5 C t~J I S

_ _ T _ T 5 5 Lr o: 5 ~r 5 T 5 T 5 ~ ~j 133931~

-1o1-Preparation of cis- and trans-methyl 2-(4-isopropyl-4-methyl-5-thioxo-2-imidazolidinyl)nicotinate ~ OOCH3 fH3 11 +NH2~--CSNH2 CHO
N CH(CH3)2 COOCH3 ~ COOCH3 N ~ '~_-CH(CH3)2 ~N ~ N\' 3 CH(CH ) HN- - S HN - S

Using essentially the same conditions as described in Example 35, but substituting 2-amino-2,3-dimethylthiobutyramide for 2-amino-2,3-dimethylbutyramide gives a mixture of cis- and trans-methyl 2-(4-isopropyl-4-methyl-5-thioxo-2-imidazolidinyl)nicotinate from which essentially pure trans-isomer, mp 127-129~C can be isolated by chromatography of the crude product on silica gel. The melting point of the cis-isomer is 142-143.5~C.

3o 13~9315 Preparation of cis- and trans-ethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl-2-yl)~uinoline-3-carboxylate ~cooc2H5 fH3 W~ ~,LCHO + NH2~0NH2 N CH(CH3)2 ~CO OC 2 H5 CO OC 2 H5 W' N J'~ ~--CH ( CH3 ) 2 W' N ~ ~_-CH ( CH3 ) 2 Using essentially the same procedure as described in Example 35, but substituting ethyl 2-~ormyl-quinoline-3-carboxylate [Godard etal., Bull. Chem. Soc.
France, 906 (1971)] for the methyl 2-formylnicotinate, there is formed the cis-ethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)quinoline-3-carboxylate, mp 156-164~C and trans-methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)quinoline-3-carboxylate, mp 163-164~C. Following the procedure of Example 33 but substituting a substituted 2-formylcarboxylate and using an appropriately substituted aminoamide in place of 2-amino-2 t 3-dimethylbutyramide will give the substi-tuted formula IV 2-(2-imidazolidinyl)quinoline-3-carboxylate.
3o - -103- ' 13~31~

Preparation of ethyl 2-[2-(dimethylamino)vinyl]-5-nitronicotinate ~2Nf ~OOC2H5 (CH3)2NCH(OCH3)2 02N~XOOC2H5 H=CH-N(CH3)2 A solution containing 20.88 g of ethyl 2-methyl-5-nitronicotinate in 100 mL l,l-dimethoxytri-20 ethylamine is heated at reflux for three hours and 15minutes. The mixture is cooled and the solid collected by filtration, washed with methanol and air dried to give 26 g of the desired enamine as a dark red solid mp 176-179~C.

-104- 13~3~15 Preparation of ethyl 2-[N-(l-carbamoyl-1,2-dimethyl-propyl)formimidoyl]-5-nitronicotinate .

02N ~ OoC2H5 H=CH-N(CH3)2 N

1. 03,(CH3)25 fH3 2. NH2 -C - CONH2 CH(CH3)2 ~2 ~ ooc2H5 fH3 CH= N - C - CONH2 N
CH(CH3)2 To a solution containing 18.9 g of the enamine in 200 mL CH2C12 and 10 mL methanol cooled in an ice 25 bath is added ozone from a Welsback ozone generator operated at 120v and air at 8 psi. This is continued until the red color of the enamine is discharged. The ozone is replaced by nitrogen and then 10 mL dimethyl-sulfide added. After 15 minutes, 9.8 g of 2-amino-2,3-30 dimethylbutyramide is added, the reaction mixture trans-ferred to a 500 mL flask and concentrated. The residue is dissolved in 300 mL toluene and heated at reflux under a nitrogen atmosphere under a Dean-Stark water trap. After one hour, the so~vent is removed and the 35 residue, a black gum, which is mainly the Schiff base is used without further purification.

Preparation of cis- and trans-ethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-5-nitronicotinate 02N ~ oOC2H5 fH3 CH= N - ,C - CONH2 CH(CH3)2 TFA

~ COOC2H5 / ~ N C~H3 HN---{=O

02N ~ ~~C2 H5 / ~ N CH3 HN---'=0 133931~

The crude Schiff base as described above is dissolved in 50 mL CH2C12 and treated with 4.6 mL tri-fluoroacetic acid at room temperature. After one hour an additional 1 mL acid is added and stirring continued for one hour. The mixture is cooled, 5.5 g sodium bicarbonate added. After the slow and careful addition of water, stirring is continued until CO2 evolution ceases. The pH is adjusted to 7 with saturated sodium bicarbonate solution and the CH2Cl2 layer removed. The aqueous phase is reextracted three times with CH2Cl.
The combined extracts are dried and concentrated to give the crude product as a dark semi-solid. This material is chromatographed on silica gel. Using ether and hexane-ethyl acetate mixtures to develop and elute the products, trans-ethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazoliinyl)-5-nitronicotinate is eluted first and is recrystallized from CH2Cl2-hexane to give the pure trans-isomer mp 116-120~C.
The cis-isomer is eluted later and is recrys-tallized from CH2C12-hexane to give pure cis-ethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-5-nitro-nicotinate mp 149-150.5~C.

Preparation of methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-5-(methylthio)nicotinate Br~COOCH3 - N ~ / N\__{H(CH3)2 HN - O

NaSCH3 I HF/DMF

CH3S ~ COOCH3 N ~ {H(CH3)2 HN - _ O

To a stirred solution containing 1.0 g bromo compound in 5 mL THF and 2 mL DMF is added 210 mg sodium methyl mercaptide under nitrogen. After two hours at 60~C, the mixture is cooled to room temperature, the pH
adjusted to 4 with acetic acid, poured over ice and extracted with 2 x 50 mL ether. The extract is dried and concentrated to give a yellow oil which slowly solidifies. Recrystallization of the solid from ether/hexane gives pure methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-5-methylthio)nicotinate, mp 107-108~C.

Preparation of dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate I ~ NHC02Prl ~ ~ NH2 DMAD

S POC13/DMF ~ S ~CO2cH3 ICC02CH3 L ~ /,~Co2cH3 H

A mixture of isopropyl-3-thiophenecarbamate (177 g; 0.975 mol) in methanol (1.2 l) and water (2.8 l) containing sodium hydroxide (200 g) is heated at reflux for four hours. Methanol is removed under reduced 2 pressure and the cooled reaction extracted with ether (5 l), and these extracts are washed with water, aqueous sodium chloride and dried. Evaporation under reduced pressure affords 3-aminothiophene as an oil in 57p crude yield.
3-Aminothiophene is redissolved in methanol (500 mL) cooled in an ice bath and dimethylacetylene-dicarboxylate (80 g; 0.50 mol) is added dropwise. The mixture is stirred at room temperature for 15 hours and 30 minutes, the methanol removed under reduced pressure 3 and 1,2-dichloroethane is added. This solvent is also evaporated off to give dimethyl 3-thienylaminobutene-dioate as an oil.

A Vilsmeier reagent is prepared by adding dropwise, with stirring phosphorus oxychloride (86 g, 0.56 mol) to a cooled (5~C) solution of DMF (41 g, 0.56 mol) in 1,2-dichloroethane (200 mL). This reagent is stirred at room temperature for one hour and 40 minutesr diluted with 1,2-dichloroethane (lOO mL), cooled to 5~C and then the above dimethyl ester dis-solved in 1,2-dichloroethane (400 mL) is added to the Vilsmeier reagent at 5~C dropwise over a 25 minute~ lO period. The reaction temperature is raised to room temperature for 15 minutes, then to reflux for a further two hours and 25 minutes. The cooled reaction mixture is chromatographed directly on a silica gel column affording 35.7 g (15~) of dlmethyl thieno[3,2-b]-pyridine-5,6-dicarboxylate mp 124-125.5~C after crystal-lization from hexane-ethyl zcet2te. A second crop (10.3 g) with mp 121-124~C is obtained giving an overall yield from isopropyl 3-thiophenecarbamate of 19p.
Utilizing the above procedure and substituting the 2ppropriate substituted aminothiophene for isopropyl 3-aminothiophenecarbamate yields the compounds illus-trated below.

R9~ S ~COOR "
Rlo COOR"

R9 Rlo R" mp~C

Cl H CH3 1339~15 - 1 1 o -Preparation of dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate S ~ CHO l. H2S~4 ~ S ~ 02CH3 NHCOCH3 3 POC13/DMF ~ / ~ 02CH3 To concentrated sulfuric acid (170 mL), stirred at room temperature is added in portions 3-acetylamino-2-formylthiophene (17.5 g, 0.103 mol). The mixture is heated at 50~C for 30 minutes, cooled and poured into an ice-water mixture. After neutralizing with an excess of sodium acetate, the mixture is ether (l x 2 l) extracted. The organic layer was dried over anhydrous Na2S04 and stripped to a dark red gum consistin~ of 3-amino-2-formylthiophene. Dimethylacetylenedicarbo-xylate (DMAD) (13 mL) in acetic acid (5 mL), piperidine (5 mL), methylene chloride (100 mL) and toluene (lOO mL) is added to the 3-amino-2-formylthiophene and the mix-ture stirred overnight. Methylene chloride is removed by distillation and then the mixture heated at reflux for 24 hours. After cooling an additional 13 mL of DMAD is added and the reaction heated to reflux again for seven and one-half hours. After standing for 60 hours at room temperature, the solvents are removed and the dimethyl thieno[3,2-b]pyridine-5,6-dicarboxylate product is obtained by chromatography, after eluting with hexane-ethyl acetate, mp 124-125~C.

l3393ls Preparation of dimethyl 3-chloro[3,2-b]pyridine-5,6-di-carboxylate and dimethyl 2,3-dichlorothieno[3,2-_]-pyridine-5,6-dicarboxylate ~~É02CH3 ~S~c02cH3 Cl 02CH3 ClN C02CH3 A solution of dlmethyl thieno[3,2-b]pyridine-5,6-dicarboxylate (15 g 0.0525 mol) in acetic acid (680 mL) and sodium acetate (86 g, 0.093 mol) is main-tained at 58~C while chlorine is slowly introduced during five hours and 45 minutes. After reaction is complete, the mixture is flushed with nitrogen, ethylacetate (200 mL) is added and solid sodium chloride filtered off and washed with ethyl acetate. The mother liquors and washes are combined and the solvents removed under reduced pressure. The residue is dissolved in methylene chlor_de and the solution washed with water, back extracted with methylene chloride and the combined methylene chloride layers washed with aqueous sodium bicarbonate, dried and stripped to give 18 g of solid.
Chromatography on silica gel with 15p ethyl acetate-hexane, then 20p ethyl acetate-hexane gives the 2,3-dichloro compound, mp 173-178~C, 1.3 g, followed by the 3-chlorothieno compound mp 166-173~C after crystalliza-tion from ethyl acetate-hexane.

Preparation of dimethyl 3-bromothieno[3,2-b]pyridine-5,6-dicarboxylate i~ ~ Br2 ~ C02CH3 C02CH3 Br C02CH3 N N

A solution of bromine (20 g, 0.125 mol) in acetic acid (50 mL) is added dropwise over three hours to a solution of dimethyl thieno[3,2-b]pyridine-5,6-di-carboxylate, (26.3 g, 0.104 mol), containing sodium acetate (17.2 g, 0.2 mol) in acetic acid (300 mL) at 85~C. Additional sodium acetate (18 g) and bromine (20 g) in acetic acid (50 mL) is added over an hour and the mixture stirred at 85~C overnight. Bromine (10 g) is added in one portion then left at 85~C for four hours. The mixture is cooled and treated with aqueous sodium bisulfite, diluted with ethyl acetate and con-centrated. The reaction product is partitioned between water and methylene chloride and the organic layer washed with aqueous sodium chloride and the solvent removed. The residue is washed with ether to give 25 g of crude product, mp 165-168~C. Recrystallization from methanol gave needles of dimethyl 3-bromothieno[3,2-b]-pyridine-5,6-dicarboxylate, mp 168-169~C.

3o -113- 133931~

Preparation of thieno[3,2-b]pyridine-5,6-dicarboxylic acid --CO 2 CH 3 Na O H , L,~cco 2 H

N N

Dimethyl thieno[3,2-b]pyridine-5,6-dicarboxy-late (3.75 g, 0.0149 mol) is added to a solution of sodium hydroxide (1.8 g, 0.045 mol) in water (20 mL) and the mixture is warmed at 60~C for 20 hours. The 5 reaction mixture is diluted with water, cooled in an ice bath, and acidified by the addition of concentrated hydrochloric acid. A precipitate of thieno[3,2-b~-pyridine-5,6-dicarboxylic acid is filtered off and dried overnight to give 3.1 g (93p) mp >380~C.
2 Utilizing the above procedure and substituting the appropriate substituted thieno[3,2-b]pyridine-5,6-dicarboxylic acid diester yields the compounds illus-trated below.

R9 ~ S ~ C02H

Rl o C02H
N
3o Rg Rlo mp~C
H H >380 H Cl None taken H Br >380 H
H F
H CN

H OH

H N(CH3)2 H SO2N(CH3)2 C6Hs H
-(CH2)3-_(CH2)4--(CH)4-Cl Cl 3o 1339~31~

Preparation of 3-chlorothieno[3,2-b]pyridine 5,6-dicarboxylic acid anhydride ~ S ~ - COOH A O

3-Chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid (1.45 g) is heated at 85 to 90~C for 30 minutes then 90 to 102~C for 30 minutes in acetic anhydride (7 mL). The reaction is cooled, the solids filtered off and washed with ether to give 1.2 g of 3-chloro-thieno[3,2-b]pyridine-5,6-dicarboxylic aci~ anhydride.
Utilizing the above procedure and substituting the appropriate pyridine-5,6-dicarboxylic acid for 3-chlorothieno[3,2-b]pyridine-5,6-dic2rboxylic acid yields the compounds illustrated below.

R9 ~ S

Rlo N

3o 13~93 1 5 Rg Rlo mp~C

H Cl Solid no mp ' obtained H Br >380 Cl H
Cl Cl N(CH3)2 H F
H

H CN

H S02N(CH3)2 -(CH2)3--(CH2)4--(CH)4-Cl C1 3o 133931~i Preparation of 5-[(1-carbamoyl-1,2-dimethylpropyl)-3-chlorothieno[3,2-b]pyridine-6-carboxylic acid Cl ~ ~ ~ + NH2- f { ONH2 N CH(CH3)2 o ! ~ OOH fH3 Cl N ONH ~ { ONH2 CH(CH 3 ) 2 2-Amino-2,3-dimethylbutyramide (0.71 ~) 211 in one portion is added to a stirred solution of 3-chloro-thieno[3,2-b]pyridine-5,6-dicarboxylic acid anhydride, (1.2 g) in THF (1.0 mL). After standing for five minutes, the ice bath is removed and the reaction st~rred at room temperature for 28 hours. T~F (5 mL) is added and the mixture heated at reflux for two hours and then set aside overnight. The cooled mixture is filtered and the collected solid washed with ether to gi~e 1.4 g of the desired 5-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]3-chlorothieno[3,2-~]pyridine-6-carboxylic acid.
Utilizing the above procedure and substituting the appropriate pyridine-5,6-dicarboxylic acid anhydride for 3-chlorothieno[3,2-b]pyridine-5,6-dicarboxylic acid anhydride and the appropriate aminoamide yields the compounds illustrated below.

-118~ 3931~

R9~ CC~2H ~1 Rl o CO NH--Cl ~0 NH 2 Rg R10 R1 R2 mp~C
H H CH3 1_C3H7 H Cl CH3 l-C3H7 not p~re 10 Cl H CH3 1-C3H7 Cl Cl CH3 l-C3H7 H Br CH3 l-C3H7 H Me CH3 l-C3H7 H NO2 CH3 l-C3H7 H N(CH3)2 CH3 l-C3H7 H SCH3 CH3 l-C3H7 H OCH3 CH3 l-C3H7 CH3 H CH3 l-C3H7 H SCH3 CH3 l-C3H7 H CN CH3 l-C3H7 H I CH3 l-C3H7 H SG2N(CH3)2 CH3 1-C3H7 -(CH2)3- CH3 1-C3H7 -(CH2)4- CH3 1-C3H7 -(CH)4- CH3 1-C3H7 H C6H5 CH3 l-C3H7 35 CF3 H CH3 i_C3H7 13~93 1~

~ EXAMPLE 22 Preparation of 5-(4-isopropyl-4-methyl-5-oxo-2-imidazo-lin-2-yl)thieno[3,2-_]pyridine-6-carboxylic acid ~02H

NH2 - f- CONH2 . ~ 02H fH3 CH(CH3)2 CONH ~ - CONH2 CH(CH3)2 1. NcOH
2. H+

~ N CH(CH3)2 N

Thieno[3,2-b]pyridine-5,6-dicarboxylic acid (2.5 g, 0.011 mol) is heated slowly to 85~C for one hour with acetic anhydride (25 mL), then cooled, filtered and washed with diethyl ether to give the anhydride as 3o a solid, mp 266-267~C. A mixture of the anhydride and 2-amino-2,3-dimethylbutyramide (2.6 g, 0.02 mol) in T~F
(70 mL) is stirred at room temperature for 15 hours.

After heating at reflux for two hours, the mixture is cooled and diluted with THF (50 mL). Solid 5-[(1-car-bamoyl-1,2-dimethylpropyl)carbamoyl]thieno[3,2-b]-pyridine-6-carboxylic acid is filtered off, washed with ether and dried. The above solid is mixed with an aqueous 60 mL) solution of sodium hydroxide (6 g 0.05 mol) and heated at 85~C for two hours and 30 minutes, then set aside at room temperature overnight.
After cooling in an ice bath, the mixture is acidified to pH 3 with concentrated hydrochloric acid. A solid (3 g) is filtered off and dried. Crystallization from ethyl acetate affords (5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[3,2-b]pyridine-6-carboxylic acid, mp 242-244~C in 46% yield.
Utilizing the above procedure and substi-tuting the appropriate pyridine-5,6-dicarboxylic acid for thieno[3,2-b]pyridine-5,6-dicarboxylic acid yields the compounds illustrated below.

-121- 1~3~3 ~ ~02H CH3 Rlo /~/N\ - CH(CH3)2 Rg Rlo mp~C

H Cl 238-239 H Br 226-227 Cl H 266-267 H

~,p 239- 241~C

133~315 Preparation of diethyl furo[3,2-~]pyridine-5,6-dicarboxylate ~c ~=02C2H~
NH 2 ~ 2C2 H5 3-Amino-2-formylfuran, prepared from 3-azido-2-formylfuran (8.9 g 0.065 mol) is dissolved in ethanol and to this solution diethyl oxzlacetate (12.23 g, 0.065 mol) and ten drops of piperidine are added. In addition pulverized 3A~ molecular sieve is added and the reaction stirred at 65-60~C for three hours, then additional diethyl oxalacetate (2.2 g) is added. The reaction is essentially complete after 12 hours at 55-60~C. On cooling the reaction is filtered, and the filtrate concentrated and then dissolved in ethyl acetate, water washed, then brine washed, dried over anhydrous magnesium sulfate and stripped to dryness.
The residue is dissolved in 3:1 hexane:ethyl acetate and passed through a flash chromatographic column in two stages. First it is filtered by vacuum through a four to five inch pad of silica from which the last three fractions containing the required product are collected and combined. These combined fractions are then passed through a six inch column eluting under pressure with ethyl acetate:hexane 3:1 anc 2.1. Diethyl furo~3,2-bjpyridine-5~6-dicarboxylate 4.15 g (24~) is obtained after crystallization from hexane-ether, of mp 60-64~C, and with a mass spectrum m/e of 264.

133931~

Utilizing the above procedure and substituting the appropriate furan for 3-amino-2-formylfuran yields the compounds illustrated below.
R 9~ ~ ~~ 2 R "

Rlo 02R
N

Rg R10 R" mp~C

H ClC2H5 3o -124- 1 ~3931 5 Preparation of furo~3,2-b~pyridine-5,6-dicarboxylic acid ~ ~2C2H~ ~N

Furo[3,2-b]pyridine-5,6-dicarboxylic acid, diethyl ester (1.1 g, 0.0042 mol) is dissolved in 95p ethanol (20 mL) containing lOd aqueous sodium hydroxide (20 mL) and set aside at 0~C for t~o days. The mixture is cooled, acidified and the solvent removed under reduced pressure. Water 5 mL is added and the hydrated product diacid obtained as a brown solid by filtration, 3.31 g (99%), mp 183~C (dec). Anal calcd. as CgH5N05.2 1/2 H20 C, 42.86; H,3.99; N,5.55 found:
C,42.63; H, 2.63; N,5.46.

3o - 1~3~31~

Preparation of furo[3,2-b~pyridine-5,6-dicarboxylic acid anhydride ~ C02H

Euro[3,2-b]pyridine-5,6-dicarboxylic acid (3.3 g, 0.0159 mol) in acetic anhydride (100 mL) is heated to 70-80~C for six hours. The reaction mixture is cooled, filtered and the solid is washed with ether to give 3.0l (100%) of crude furo[3,2-b]pyridine-5,6-dicarboxylic acid anhydride.

3o 133~3~5- --l26-Preparation of 5-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]furo[3,2-b]pyridine-6-carboxylic acid and 5-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo-[3,2-b]pyridine-6-carboxylic acid C~/~ fH(CH3)2 ,1 H 2 N~--C O N H 2 N ~ CH3 o ~2H fH3 N
CH(CH3)2 l. NaOH
2. Acid ~ ~ O~H CH(CH3)2 N N~ ~
3o -127- 13~931~

Furo[3,2-b]pyridine-5,6-dicarboxylic acid anhydride (3.01 g, 0.015 mol) is suspended in THF
(100 mL) to which 2-amino-2,3-dimethylbutyramide (2.3 g, 0.018 mol) is added. After stirring for 20 hours, the solution is stripped to an oily solid which dissolves in a water/dilute sodium hydroxide solution.
The alkaline solution is extracted with methylene chloride, and then acidified and reextracted with 0 methylene chloride but on stirring only minute traces of material is isolated. The water layer is concentrated to an oily solid which is dissolved in ethanol, filtered and concentrated to a purple gum which is predominantly the crude product, 5-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]furo[3,2-b]pyridine-6-carboxylic acid and is used without further purification to prepare the final 2-imidazolin-2-yl product by dissolving it in 10%
sodium hydroxide solution (40 mL) and warming at 80~C
for three hours. On cooling the reaction is acidified and a small amount of solid precipitated out and was filtered off. Concentration of mother liquors gives a second crop, which is collected and combined with the first crop. Purification is effected by taking half of the material and separating on silica gel preparative glass plates as bands. The slower running band using methylene chloride:ethyl acetate:chloroform: methanol 1:1:1:1 as eluant, affords the desired 2-imidazolin-2-yl product, mp 214-223~C(dec), Esters may then be prepared by the procedures described in Example 20.

13~9315 Utilizing the above procedure and substituting the appropriate furo[3,2-b]pyridine-5,6-dicarboxylic anhydride yields the compounds illustrated below.

~ ~~ 2 H CH 3 Rlo /~--// N--CH(CH3)2 N
N - ~

Rg Rlo mp~C
H H 214-223 (dec) H Cl 1339~ 1 ~

Preparation of dimethyl thieno[2,3-b]pyridine-5,6-dicarboxylate C02CH3 DMF ~rC02CH3 C02CH3 POC13 ~ 1 /~C02cH3 A Vilsmeier reagent is prepared by adding dropwise, with stirring, phosphorus oxychloride (40.29 g, 0.26 mol) to a cooled (10~C) solution of DMF
(l9.0 g, 0.26 mol) in 1,2-dichloroethane (40 mL) in an N2 atmosphere. This reagent is stirred at room temperature for one hour and 45 minutes. Dimethyl-2-thienylaminobutenedioate (63.4 g, 0.26 mol) dissolved in 1,2-dichloroethane (300 mL) is added dropwise to the Vilsmeier reagent at 7-10~C. The reaction temperature is raised to room temperature for 15 minutes, then to reflux for 12 hours. The cooled reaction mixture is concentrated and the residue chromatographed on a silic2 gel column with ethyl acetate-hexane, affording dimethylthieno[2,3-b]pyridine-5,6-dicarboxylate (29 g, 45Z) as a solid.

3o Utilizing~the above procedure and substituting the appropriate dimethyl-2-thienylaminobutenedioate yields the compounds illustrated below.

R5 ~ C02CH3 Rlo~ ~ ~) {02CH3 Rg R1o mp~C

H H solid CH~ CH3 3o -131- 133~31~

Prepzration of dimethyl 3-bromothieno[2,3-b]pyridine-5,6-dicarboxylate C02CH3 Br2 Br ~ ~ 02CH3 C02CH3 HOAc 02CH3 S N NaOAc S N

Bromine (0.33, 0.00206 mol) in acetic acid (8 mL) is added to a stirred solution of dimethyl-thieno[2,3-b]pyridine-5,6-dicarboxylate (0.5 g, 0.00187 mol) in acetic acid containing sodium acetate (0.31 g, 0.00377 mol) at 40~C. The reaction mixture is heated at 75~C for 18 hours. Evaluation of the mixture by tlc (silica gel) indicated incomplete reaction.
Additional bromine (0.33 g) in acetic acid and sodium acetate (0.31 g) is added and heating at 75~C continued for six hours. The reaction mixture is diluted with water and extracted into ethyl acetate. The separated organic layer is dried over anhydrous MgS04, filtered, and the filtrate concentrated to an oil which solidifies on standing. Crystallization of the crude product from ethyl acetate-hexanes yields the dimethyl 3-bromo-thieno~2,3-b]pyridine-5,6-dicarboxylate as white needles mp 86-87.5~C.
- This compound may readily be converted to a variety of substituted-thieno[2,3-b]pyridine compounds as illustrated below, while electrophilic substitution such as nitration or halogenation yields the additional compounds also listed be~ow.

Rl o~ 0 2 CH 3 R~ 02CH3 S N

Rc, Rlo mp~C
H H
H Cl 104-110 H Br 86-87.5 H
H - F
H CN

H N(CH3)2 H CHO
H CH2Cl Cl H
Cl Cl 84-89 H SO2N(CH3)2 -(CH2)4-3~ -(CH)4--(CH2)3-C6Hs H

-133- 133~315 Preparation of thieno[2,3-b]pyridine-5,6-dicarboxylic acid ~2CH3 KOH ~ 02H

S N S N

A solution containing dimethyl thieno[2,3-b]-pyridine-5,6-dicarboxylate (27.75 g, 0.11 mol) and potassium hydroxide (30.98 g, 0.55 mol) in methanol (200 mL) under a N2 atmosphere is heated at reflux for two hours. The reaction mixture is cooled and suffi-cient water added to dissolve any solids present before evaporating the mixture to dryness. The resulting solid is dissolved in a minimum volume of water, cooled in an ice bath and acidified with concentrated H2S04 to pH~1. Thieno[2,3-b]pyridine-5,6-dicarboxylic acid is filtered off and dried overnight to give 23.36 g mp 272-275~C.
Utilizing the above procedure and substitu-ting the appropriate substituted dialkylthieno[2,3-b]-pyridine-5,6-dicarboxylate yields the compounds illustrated below.

3o R 1 0~ ~CC~ 2 H
Rg C02H
S N

Rg Rlo mp~C

H Cl >300 H Br >315 H
H F
H CN

H N(CH3)2 H CHO
H CH2Cl H CH3 180-183 (dec) Cl H
Cl Cl C6Hs H
H SO2N(CH3)2 -(CH2)3-_(CH2)4--(CH)4-- 133~31~

EXAMPLE 30Preparation of thieno[2,3-b]pyridine-5,6-dicarboxylic anhydride ~C02H Ac 2~ ~\
~ "ko 2 H P y r, DM E
S N S N

Acetic anhydride (37.4 g, 0.366 mol) is added to a stirred suspension of thieno[2,3-b]pyridine-5,6-dicarboxylic acid (21.52 g, 0.096 mol) in dimethoxy-ethane (175 mL) in an inert N2 atmosphere. Upon addition of pyridine (16.78 g, 0.21 mol) at room temperature an exotherm to 45~C is observed and a homogeneous so~ution results. The reaction mixture is then stirred at room temperature and the resulting solid filtered off, washed with ether and air dried to give 14.8 g (75p) of thieno-[2,3-b]pyridine-5,6-dicarboxylic acid anhydride.
Utilizing the above procedure and substituting the appropriate substituted thieno[2,3-b~pyridine-5,6- -dicarboxylic acid yields the compounds illustrated below.

3o R9 ~ 5 ~

Rg R10 mp~C

H Br 228.5-231 H Cl 230-300 (slow dec) H ~, H
H
H F
H CN

N(CH3)2 H CH2Cl Cl .Cl Cl H S02N(CH3)2 -(CH2)3--(CH2)4-_(CH)4-. H C6H5 H 0c6Hs 133931~i -l37-Preparation of 6-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]thieno~2,3-b]pyridine-5-carboxylic acid ~\ fH3 1 ~ +H2N~ONH2 S N ~ CH(CH3)2 C02H fH3 CONH~{ONH2 S N
CH(CH3)2 2-Amino-2,3-dimethylbutyramide (9.84 g, 0.076 mol) is added to a stirred suspension of thieno-[2,3-b]pyridine-5,6-dicarboxylic acid anhydride (14.~ g, 0.072 mol) in TH~ under an inert atmosphere of N2 at room temperature. The dark solution is stirred at room temperature overnight and the resulting solid filtered off, washed with TH~ and air dried to give 17.35 g (72p) of 6-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]thieno[2,3-b]pyridine-5-carboxylic acid.
Utilizing the above procedure and substituting the appropriate substituted thieno[2,3-b]pyridine-5,6-dicarboxylic acid anhydride ylelds the compounds illustrated below.

1339~15 Rlo~ ~02H fH3 Rg CH(CH3)2 Rg Rlo mp~C

H Br 176-178 Cl 156-158 H H
H
H F
H CN

N(CH3)2 H CHO
H CH2Cl Cl H
Cl Cl H S02N(CH3)2 -(CH2)3--(CH2)4-_(CH)4-H OC6Hs -l39-EXAMPLE 32 13 3 ~ 31~
Preparation of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazo-lin-2-yl)thieno[2,3-b]pyridine-5-carboxylic acid 02H fH3 S N CONH - IC { ONH2 CH(CH3)2 N CH(CH3)2 S N N - O

6-[(1-Carbamoyl-1,2-dimethylpropyl)carbamoyl]-thieno[2,3-b]pyridine-5-carboxylic acid (17.35 g, 0.052 mol) is added to water (225 mL) containing sodium hydroxide (10.35 g, 0.26 mol). The resulting basic solution is heated at 80~C for two hours and 45 minutes, cooled in an ice-water bath and acidified with 6N H2S04.
The product 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carboxylic acid is filtered off, washed with water and air dried yielding 1.54 g, 70.3%, mp 221-223~C.

133931~

-l40-Preparation of 2-isopropyl-2-methyl-5H-Imidazo[1',2':1,2]-pyrrolo[3,4-_}thieno[3,2-_]pyridine-3(2~),5-dione c=0 N CH(CH3)2 DCC

N~ \~ CH(CH3)2 Dicyclohexylcarbodiimide (1.07 g, 0.005 mol) 2 in methylene chloride (20 mL) is added dropwise to a stirred methylene chloride (30 mL) suspension of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno-[2,3-b]-5-carboxylic acid (1.5 g, 0.0047 mol) under an N2 atmosphere. After stirring the reaction mixture for 16 hours, it was clarified by filtration, concentrated to dryness and the resulting material purified by column chromatography on silica gel eluting with acetonitrile/
methylene chloride (1/2). The solid product was crystal-lized from toluene to give the pure 3,5-dione as white 3~ crystals mp 214.5-216.5~C.

1~3931~

Preparation of 2-propynyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[2,3-b]pyridine-5-carbo-xylate < H O H 2 CC _ CH
S N N CH(CH3)2 ~ 02CH2C-CH
/~ H
S N ~N~o N CH(CH3)2 Sodium hydride (2.4 g, 60p, 0.126 mol) is added to the 3,5-dione (0.9 g, 0.003 mol) in propargyl alcohol (25 mL) at 10~C under an inert N2 atmosphere.
The reaction mixture is stirred at room temperature for 60 hours and then neutralized with a saturated ammonium chloride solution. The resulting mixture is concentrated on a rotary e~aporator, diluted with water and extracted with ethyl acetate. The organic layer is separated, dried over anhydrous MgSO4 and concentrated to dryness.
Purification of the product by column chromato-graphy on silica gel with methylene chloride/acetonitrile (85/15) yields 2-propynyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)pyridine-5-carboxylate, which after crystallization from toluene has a mp 188-189.5~C.

Utilizing the procedures of Examples 49, 55, 56 and 57 and substituting the appropriate thieno or furo[3,2-b.]pyridine or thieno or furo[2,3-b]pyridine compounds, yields the compounds illustrated below.

R~ ~ ~ /N CH3 ~ N N - 0 1 B Rg Rlo R mp~C

S H H H 220-223.5 (dec) S H H -CH2C_CH 188-189.5 -CH

S H H -CH2~=CH2 108-110 S CH3 H H 225~5-227.5 S H Br H 274-276 S H Cl H 266-267 S H No2 -CH3 201-202.5~C
S H N02 H impure 3o 133931~

B Rg R l o R mp~C
S Cl H H 268 (dec) S - (CH2) 4- H 234 - 237 0 H Cl H 239 - 240 O H Br H 239 - 245 ~ C2H5 H H 170 - 172 0 C6Hs H H 244 - 245 0 H Cl CH3 137 - 141 r3 H H -CH2C_CH 150 - 156 R 9~ ~/N C H 3 N N - =0 B Rlo Rg R mp~C

S H Cl H 238 - 239 S H Br H 226 - 227 S H H ~ 156 - 157 S Cl H H 266 - 267 ~144-Preparation of methyl 5-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)furo~3,2-b]pyridine-6-carboxylate ~N N~ O

1 0 NaCNBH3 ~ ~I H CH(CH3)2 N ~ CH3 N --O

A solution of 22.1 mmol of methyl 5-(4-iso-propyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[3,2-b]-pyridine-6-carboxylate in methanol is cooled to 0~C and a few drops of methyl orange indicator added. The solution is stirred and treated with 22.1 mmol of concentrated hydrochloric acid. The solution is then treated with 22.1 mmol of sodium cyanoborohydride, and the pH maintained at ~3 by the additon of 2N methanolic HCl, stirred overnight, cooled to 0~C and the pH of the solution adjusted to about O with HCl to decompose residual NaCNBH3. The pH is thereafter adjusted to 5-6 - with 5N NaOH. The methanol is removed in vacuo and 3~ water added to dissolve inorganic salts. The mixture is extracted with CH2C12 and the extracts dried and concentrated to give the title compound.

133331s Utilizing the above procedure with the appro-priately substituted methyl 2-(2-imidazolin-2-yl)-furo[3,2-b]pyridine-6-carboxylate yields the corres-ponding 2-(2-imidazolidinyl)furo[3,2-b]pyridine-6-carboxylate. Similarly, reaction of the appropriately substituted methyl 2-(2-imidazolin-2-yl)thieno[3,2-b]-pyridine-6-carboxylate yields the corresponding methyl 2-(2-imidazolinyl)thieno[3,2-b]pyridine-6-carboxylate.
The reaction products are illustrated below:

R 9~ \~O OCH 3 RlO ~ N CH3 N ~ / --CH(CH3 )2 HN ~

Similarly, using the above procedure with the appropriately substituted methyl 2-(2-imidazolin-2-yl)-dihydrofuro- or dihydrothieno[3,2-b]pyridine-6-carbo-xylate yields the corresponding substituted methyl 2-(2-imidazolidinyl)dihydrofuro- or dihydrothieno-[3,2-b]pyridine-6-carboxylate. The reaction products are illustrated below:

R ll ~ ~ 0 OCH 3 Rl 2 1~ N/~ N--CH ( CH3 ) 2 3~ HN~

B W Rg Rlo mp~C

S S H H

0 O H Cl S S H Cl S 0 H Cl 10 0 S H Cl ~ 0 CH3 H

S ~ CH3 H

~ ~ C2H5 H

S ~ C2H5 H

~ 0 CH3 CH3 S ~ CH3 CH3 0 0 H Br S S H Br S 0 H Br 0 S H Br Preparation of cis- and trans-methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)thieno[2,3-b]pyridine-5-carboxylates ~S ~ N ~ / N CH(CH3)2 HN~O

Na CNB H 3 N \ I ~3HOCCHH33 IICH(CH3)2 Hl IICH(CH3)2 Using essentially the szme procedure as described in Example 58 but substituting methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)thieno[2,3-b]-~
pyridine-5-carboxylate for methyl 5-(4-isopropyl-4-methyl-5-oxo)-2-imidazolin-2-yl)furo[3,2-b]pyridine-6-carboxylate yields the two products cis-methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)thieno[3,2-b~-pyridine-5-carboxylate mp 185-186~C and trans-methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl~thieno-3~ [2,3-b]pyridine-5-carboxylate mp 145-148~C.

-148_ 133~315 Utilizing the above procedure with the appro-priately substituted methyl thieno-,dihydrothieno-, furo- or dihydrofuro[2,3-b]pyridine-5-carboxylate yields the reaction products illustrated below.
.

Rlo ~ OOCH3 R9 ~ 1 ~1 N CH3 and B N ~ ~ CH(CH3)2 HN - W

R12 ~ OOCH3 Rll /~ N CH3 B N ~ ~ CH(CH3)2 HN - -W

thus~ OOCH3 0 N ~ / ~ CH(CH3)2 yields HN~ ==O

25 ~ OOCH3 ~ OOCH3 / ~ N CH3 and O N ~ N ;
H ¦ IICH(CH3)2 Hll IICH(CH3)2 HN---~-O HN - _ O

mp 170-174~C mp 166-169~C

l3393ls Preparation of trans-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)thieno[2,3-~]pyridine-5-carboxylic acid H ~H3 HN--O

Na OH

~OOH
N ~CH3 HN--o Using essentially the same conditions as those described in Example 32 but substituting trans-methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-thieno[2,3-b]pyridine-5-carboxylate for cis-methyl 6-(allyloxy)-2-(4-isopropyl-4-methyl-5-oxo-2-imidazo-lidinyl)nicotinate gives the product trans-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)thieno[2,3-b]pyridine-5-carboxylic acid, mp 225-226~C as a sesquihydrate.

3o 133~31~

Similiary, the furano analogs yield the cor-responding imidazolidinones below:

OOH
N ~H3 HN - ~

mp 210-218~C
and OOH
~H CH3 HN _ O
mp 176-178~C

13~9~15 Preparation of diethyl 5-acetyl-l,6-dihydro-6-oxo-2,3-pyridinedicarboxylate ~ ~ ~C2Hs f~~C2H5 CH3 { { H2 { NH2 + O = C ~ { = O
CH--~C2 H5 Sadium acetate ~1 ~
CH3{~/ ~C~2c2H5 o=l~ ~CO 2C2 H5 H

Sodium acetate (30 g, 0.37 mol) is added to a stirred mixture of diethyl(ethoxymethylene)oxalacetate (87 g, 0.36 mol) and acetoacetamide (36 g, 0.36 mol) in absolute ethanol (300 mL). After stirring the reaction mixture for 30 minutes, the ethanol is distilled off under reduced pressure, the residue acidified to pH 2 with dilute aqueous hydrochloric acid and the resulting solid filtered off. Crystallization from an ethanol-water mixture affords diethyl 5-acetyl-l,6-dihydro-6-oxo-2,3-pyridinedicarboxylate as crystals mp 200-209~C.
3o 133931~

Preparation of diethyl 5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate CH3-C ~ 02C2H5 Br2 BrCH2- ~ 02C2H5 0 02C2Hs HBr O 02C2Hs N N

Bromine (8.0 g, 0.050 mol) in 48d HBr is added dropwise to a stirred solution of diethyl-5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (14.05 g, 0.05 mol) in 48~ ~Br (200 mL). Upon com-pletion of this bromine addition the reaction mixture is poured onto ice (200 g) and the mixture is stirred until the ice has melted. The crude product is col-lected by filtration and crystallized twice from an ethyl acetate-hexane mixture (1/2) affording diethyl 5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate with mp 141-142~C.

Preparation of diethyl 5-(2-bromo-1-hydroxyethyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate and diethyl 2,3-dihydro-3-hydroxy-furo[2,3-b]pyridine-5,6-dicarbo-5 xylate B'CH2-C ~ 02C2H5 NaBH4 ~ ~ ~ C~2C2H5 i-C3H70H
N

OIH
BrCH2 { H ~ (C2H5)3N
150 ~ ~ C02C2H5 HN

011~C02C2H5 l l~ ~ 02C2H5 Sodium borohydride (2.54 g, 0.066 mol) is added in portions over a 30 minute period to a stirred suspension of diethyl 5-(bromoacetyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (57.2 g, 0.159 mol) at 10-20~C. Upon completion of the sodium borohydride addition, the reaction mixture is stirred while attaining room temperature. Ice (100 g) is added and the mixture stirred until the ice has melted. The mixture is then concentrated in vacuo and the residue crystalli~ed twice from an ethyl acetate-hexane mixture to give pure diethyl 5-(2-bromo-1-hydroxyethyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate mp 134-138~C.

1~39315 Stirring this compound with triethylamine (1.0 mL/g of solid) in methylene chloride for one hour, followed by washing the organic solution with dilute hydrochloric acid, water, brine and drying over anhydrous MgS04 yields the crude furo[2,3-b]pyridine as an oil upon removin~ the solvent in vacuo. Crystallization from a cyclohexane-toluene mixture affords pure diethyl 2,3-dihydro-3-hydroxy-furo[2,3-b]pyridine-5,6-dicarboxylate mp 73-77~C.

3o 13~9315 Preparation of diethyl furo[2,3-b]pyridine-5,6-dicarbo-xylate HO~ ,~Cco2c2H5 p-toluene sulfonic acid C02C2H5 ~ xylene O N

~(~02C2H5 ~ 2C2 Hs A xylene solution of the hydroxy-furo compound obtained in Example 61, t3.7 g) containing para-toluene sulfonic acid (0.01 g) is heated at reflux for two hours. The solution is cooled and the xylene solution decanted off. The residue is extracted with ether and the extracts combined with the xylene. Distillation of the solvents gives a yellow solid which is crystallized from a cyclohexane-toluene mixture to give pure diethyl furo[2,3-b]pyridine-5,6-dicarboxylate mp 66-77~C.

133931~

Preparation of furo[2,3-b]pyridine-5,6-dicarboxylic acid 02C2Hs KOH ~ ~ 02H
O N 02C2H5 ~ N C02H
1.0 Potassium hydroxide (5.60 g, 85~" 0.087 mol) in water (5 mL) is added to a stirred suspension of diethyl furo[2,3-b]pyridine-5,6-dicarboxylate (9.3 g, 0.035 mol) in absolute ethanol (100 mL). The reaction mixture is heated at 60~C for one hour, then cooled and anhydrous acetone added. The precipit2te is filtered off, dried, suspended in dry acetone and treated with hydrogen chloride to adjust to z pH of 2. Crystal-lization of the isolated solids from an ethyl acetate-acetone mixture affords furo[2,3-b]pyridine-5,6-dicarbo-xylic acid mp 189-192~C.

3o Preparation of furo[2,3-b]pyridine-5,6-dicarboxylic . anhydride 02H acetic anhydride O N

~0 O N

Furo~2,3-b]pyridine-5,6-dicarboxylic acid (6.7 g, 0.032 mol) is heated at 60~C for 30 minutes in acetic anhydride (l50 mL). The reaction mixture is cooled to room temperature and concentrated in vacuo .
and the residue triturated with cyclohexane-ether(5:l), filtered off and dried to give 5.35 g furo[2,3-b]-pyridine-5,6-dicarboxylic acid anhydride.

3o -158- 133931~

Preparation of 6-[(1-carbamoyl-1,2-dimethylpropyl)-carbamoyl]-furo[2,3-b]pyridine-5-carboxylic acid ~ ~ O +NH2 1 ~ONH2 ~ N ~ CH(CH3)2 O2H fH3 ONH ~ --CONH2 O N CH(CH3)2 2-Amino-2,3-dimethylbutyramide (2.1 g, 0.016 mol) is added to a stirred suspension of furo-[2,3-b]pyridine-5,6-dicarboxylic acid anhydride (3.0 g, 0.016 mol) in tetrahydrofuran (7.5 mL) and the mixture allowed to stir at room temperature for 16 hours. The reaction mixture is then stirred at 60~C for one hour, cooled to room temperature, ether added, and the solid filtered off and dried to give 5 g of 6-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]furo[2,3-b]pyridine-5-carboxylic acid mp 192-196~C (dec).

13~9315 Preparation of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazo-lin-2-yl)furo[2,3-b]pyridine-5-carboxylic acid c02H fH3 H20 O N ONH--C~ONH2 NaOH
CH(CH3)2 ~ CH(CH3)2 O N N--O

A solution containing 6-t(l-carbamoyl-1,2-dimethylpropyl)carbamoyl]furo[2,3-b]pyridine-5-carbo-xylic acid (3.8 g, 0.012 mol) in aqueous sodium hydro-xide 2.4 g, o.o6 mol) in water (40 mL) is stirred at 65~C for three hours. The reaction mixture is then heated at 75~C for one hour, allowed to cool, poured into ice, acidified to pH 2-3 and the resulting solid filtered off and dried. Crystallization from an acetone-methanol mixture affords pure 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2l3-b~pyridine-5-carboxylic acid mp 237-244~C.

3o .

133931~

Preparation of 2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-_]pyridine-5-carboxylic acid CH(CH3)2 5% Pd-C
o N ~ o ~ C02H CH3 ~ 1~ ~ ~ CH(CH3)2 o N N --0 A solution of 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[2,3-b]pyridine-5-carboxylic acid (1.7 g 0.056 mol) and 1.0 g (0.0072 mol) potassium car-oonate in 200 mL 9:1 ethanol:water is added to 100 mg 5~ palladium on carbon catalyst in a 500 mL pressure bottle. The bottle is fitted to a Parr hydrogenation apparatus, pressurized to 30 psi, with hydrogen, then sha~en at room temperature for 10 hours. The catalyst is removed by filtration through a sintered glass funnel, and the filtrate concentrated in vacuo to 10 mL. Acidi-fication of the residue to pH 2 gives a white precipi-3o tate which is removed by filtration, washed with waterand air dried to give 1.0 g (63%) of 2,3-dihydro-6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo~2,3-b]-pyridine-5-carboxylic acid as an off-white solid, mp 189-192~C.

133~315 Preparation of 4-mercaptoacetyl butyronitrile CH3CSH + BrCH2CH2CH2CN

Thiolacetic acid (49 mL, 0.69 mol) is added to potassium carbonate (93.4 g, o.68 mol) dissolved in water (150 mL). Ethanol (260 mL) is added and then 4-bromobutyronitrile is added at 15 to 28~C and the reaction mixture stirred at room temperature for 16 hours. The resulting inorganic solids are filtered o.r and the filtrate extracted with toluene. The organic layer is separated, dried over anhydrous Na2S04 and concentrated to give the desired 4-mercaptoacetyl butyronitrile as a yellow oil.

- 133931~

Preparation of dihydrothiophenimine hydrochloride CH3-C-S-CH2-CH2CH2CN HCl ~ NH HCl S

Hydrogen chloride is introduced to a cooled solution of the nitrile in methanol (220 mL) for one hour and the mixture then stirred at room temperature for 16 hours. The resulting product is filte~ed off, washed with ether and dried to give 55.38 g of dihydro-thiophenimine hydrochloride, mp 189-195~C.

EXA~PLE 49 Preparation of dimethyl ~(tetrahydro-2-thienylidene)_ amino]fumarate (and maleate)acid ~ f~2C~3 N~ HCl + C f ~02CH3 N ~C--C02CH3 5 . Dimethylacetylenedicarboxylate (0.45 mL, 0.037 mol) is added to a stirred solution of dihydro-thiophenimine hydrochloride (0.5 g, 0.0036 mol) in methanol (60 mL) containing sodium acetate (0.3 g, 0.0036 mol) under an inert N2 atmosphere at -15~C.
After stirring for 16 hours at room temperature, the solvent is removed on a rotary evaporator and the resulting mixture separated by column chromatography on silica gel eluting with a methylene chloride-aceto-nitrile mixture (19:1) yielding 0.68 g (78% yield) of 2~ the desired mixed isomeric acid esters as a yellow oil.

Preparation of dimethyl 2,3-dihydrothieno[2,3-b]-pyridine-5,6-dicarboxylate 02CH3 oxalyl chloride ll DMF
\ ~ ~ /--C02CH3 S N

~{02CH3 ,1~ ,~C02CH3 S N

A Vilsmeier reagent is prepared by adding oxalyl chloride (0.25 mL, 0.0028 mol) to a stirred solution of DMF (0.22 mL, 0.0028 mol) in 1,2-dichloro-ethane (50 mL) at room temperature in an inert N2 atmosphere. A 1,2-dichloroethane (50 mL) solution of dimethyl [(tetrahydro-2-thienylidine)amino~fumarate (and maleate) (0.0028 mol) is added to the Vilsmeier reagent and the reaction mixture heated at reflux for four hours. The reaction mixture is quenched with water, made basic with sodium bicarbonate and the organic layer separated and dried over anhydrous Na2S0~.
The solvent is removed in vacuo and the residue purified by column chromatography on silica gel, eluting with a methylene chloride-acetonitrile mixture (19:1). Crystallization from toluene-hexane affords dimethyl 2,3-dihydrothieno[2,3-b]pyridine-5,6-dicarboxylate as a white solid with mp 102-103.5~C.

Preparation of 2-isopropyl-2-methyl-5H-imidazo[1',2':1,2]-pyrrolo[3,4-b]pyridine-3(2~),5-dione OOH ~ - o N C~H3 DCC CH3 N ~/ ~ CH(cH3)2 N N CH(cH3)2 HN - - ~

To a solution containing 50.9 g of dicyclo-hexylcarbodiimide in 600 mL of dry methylene chloride is added, while stirring, 60 g of the acid at such a rate that the temperature does not exceed 32~C. After stirring at room temperature for two and one-half hours, the mixture is filtered and the filtrate concentrated to give a white solid. This solid is recrystallized from methylene chloride to give 57.4 g of the dione, mp 125-128.5~C. The analytically pure dione melts at 132-134~C. The procedure is illustrated in European Patent Application 0,041,023, published December 16, 1981.
Using essentially the same procedure but substituting the appropriate acid for 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid, the following imidazopyrrolopyridine-3,5-diones are prepared.

o o o o ~ o o o C7 o o ~ ~ U~ ~ o U~ o o o o o o o oo o CO ~ oo ,' a~ o c~ ~ ~ ~ o ~ T

._ Z

i- ~ 2 '-- 2 X--<\ Z ~2~ 2 2 ~ 2 _ -- 2 .~ b' c~ ~ 2 ~ ,2 2 2 ~ r o ~

X ¦ 2~ 2 2 2 2 2 2 2 3 1 0 0 0 0 0 0 V~

l339315 o o o o t~ a~ ~ o C'~
o~ l l l l ~ o o o o ~o ~) _, S~ ~ ~
S S S

CS~ C~

C" 0, 0, S ~ ~ .
S CS~ C~

~ I O S ~

xl S ~r S S S S

3 1 cr~ U~ o o o o l3393l5 Preparation of 3-isopropyl-3-methyl-5H-imidazo[1',2':1,2]-pyrrolo[3,4-b]pyridine-2(5H),5-dione .~\ CH 3 N N CH(cH3)2 NaOAC
Ac20 o ~ CH ( CH 3 ) 2 N N
To a solution containing 0.5 g 2-isopropyl-2-methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-3(2H), 5-dione in 5 mL acetic anhydride is added 50 mg sodium acetate and the mixture heated at reflux for two hours.
The solvent is removed and the product extracted into ether to give the rearranged dione, 3-isopropyl-3-methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-2(3H)5-dione mp 107-115~C.

5~ 00 HCH
CH(CH3)2 HN----S

10( CF3CO ) 2~

~\ S

To a solution of the acid in 200 mL toluene and 100 mL CH2C12 under nitrogen is added with stirring at -60~C during 0.5 hours, 1.9 g trifluoroacetic anhy-dride dissolved in 18 mL toluene and 7 mL CH2C12. After this reaction, 500 mL hexane is added and the mixtu.e concentrated in vacuo to give a dark green solid. NMR
spectroscopy showed this to consist of 80% of the desired 2,5-dione and 20% of 3,5-dione.

The 2,5-dione was characterized as its water addition product, mp 162-165~C with structure ~ CH3 ~ ~ N CH(CH3)2 ~\ ~1~ S
OH
Using essentially this procedure or those described in Examples 51, 52 and 52-A and starting with the appropriate acid or 3,5-dione, the following 2,5-diones are obtained.

Y /'~' N R2 Z~\ ~\ ~
N N
W X Y Z Rl R2 mp~C
O H H C3H7 C~3 CH(CH3)2 O H H CH(CH3)2 CH(CH3)2 O H CH(CH3)2 H CH3 CH(CH3)2 O 11 C2H5 H CH3 CH(CH3)2 O H H C2H5 CH3 CH(CH3)2 O H OCH(CH3)2 H CH3 CH(CH3)2 S H H H CH3 CH(CH3)2 S H CH3 H CH3 CH(CH3)2 .
S H C21~5 H CH3 CH(CH3)2 S H -CH=CH-CH=CH- C113 CH(CH3)2 ~-~

c~

W X Y Z Rl R2 mp~C
S H -CH=CH-S- CH3 CH(CH3)2 S H -CH=CH~O- CH3 CH(CH3)2 O H H OCH3 CH3 CH(CH3)2147.0 - 147.5 O H OCH3 H CH3 CH(CH3)2 o H ~3 H ~3 CH(CH3)2 133~31s The procedures of Examples 51, 52 and 52-A
may be graphically illustrated as follows:

Y ~ O O H

N ~ / N - R2 HN W

DCC

( C F 3 CO ) ~ O Y~ ~_W AC ~ O/HO A c when W = S z Rl when W = O

HOAc/Na OAc , ~ \

N N

NaBH4 J 3~ Rl N ~ HN

1339~1~

Postemergence herbicidal evaluation of test compounds The postemergence herbicidal activity of the compounds of the present invention is demonstrated by the following tests, wherein a variety of monocotyledo-nous and dicotyledonous plants are treated with test compounds dispersed in aqueous acetone mixtures. In the tests, seedling plants are grown in jiffy flats for about two weeks. The test compounds are dispersed in 50/50 acetone/water mixtures containing 0.5% TWEEN~ 20, a polyoxyethylene sorbitan monolaurate surfactant of Atlas Chemical Industries, in sufficient quantities to provide the equivalent of about .016 to 10.0 kg per hectare of active compound when applied to the plants through a spray nozzle operating at 40 psig for a pre-determined time. After spraying, the plants are placed on greenhouse benches and are cared for in the usual manner, commensurate with conventional greenhouse practices. From four to five weeks after treatment, the seedling plants, are examined and rated according to the rating system provided below. The data obtained are recorded in Table V below.
% Difference in Growth Rating System from the Check 25 0 - No Effect ~
1 - Possible effect 1-10 2 - Slight effect 11-25 3 - Moderate effect 26-40 5 - Definite injury 41-60 6 - Herbicidal effect 61-75 7 - Good herbicidal effect 76-90 8 - Approaching complete kill 91-99 9 - Complete kill 100 4 - Abnormal growth, that is, a definite physiological malformation but with an over-all effect less than a 5 on the rating scale.

133~

In most cases the data are for a single test, but in several instances, they are average values obtained from more than one test.
Plant Species Used Barnyardgrass (Echinochloa crusgalli) Green foxtail (Setaria viridis) Purple Nutsedge (Cyperus rotundus L.) Ragweed (Ambrosia artemisiifolia, L.) 10 Quackgrass (Agropyron repens) Field Bindweed (Convolvulus arvensis L.) Morningglory (Ipomoea purpurea) Velvetleaf (Abutilon theophrasti) Cotton (Gossypium hirsutum, L.) 15 Corn (Zea mays) Soybean (Glycine max) Bragg Soybean (Glycine max) Williams Wheat (Triticum aestivum) Rice (Oryza sativa) Nato TABLE V

POST-EMERGEIICE TEST9 ~~ RATES rll KG/~IA
E1AR~IY FOXTA P IIUT ~UACK FLO E ~IRIIGL RAG~E VELVE CORII COTTO RICE SOY~E S~Y~E S WIIE
Compound RATE ARDGR IL SPSEOGE GnA55 IIIO~IDRY SP _____ TLEAf FIELO t~ NATO AN ERAll wr AT ER
3~-Ethyl-1,9b~(and ~)-di- lo.ooo 7.0 0.0 2.0 B.O
hydro-3-methyl-5H-imidazo- 1-000 00 0 0 0 4 0 1 0 7 00 0 0 0 00 0 0 0 [1',2':1,2]pyrrolo[3,4-b]- 250 0.0 0.0 ~.0 0.0 7.0 0.0 0.00.0 0.0 pyridine-2(3H),5-dione .125 0.0 0.0 1.0 0.0 6.0 0.0 0.00.0 0.0 - .0~3 0.0 0.0 4.0 0.0 ~.0 0.0 0.0O.0 0.0 1,9b~L(and ~)-dihydro-3~L- l ooo 9.0 B.O 9.09.09.09.09.0 B O 90 7 5 9090 isopropyl--3--methyl--5H--.soo B.0 7.0 9.09.09.0 B.O 9.0 7.5 9.05.0~ 8.59.0 imidazo[l' 2'-1,2]pyrrolo- .250 2.0 2.0 B.0 9.09.08.09.05.09.0 5.0~ 8.0 B.S
[3,4--b]pyridine--2(311),5-- 125 1 0 0 0 2 0 90 B O lB 09 ~ l S 8 0 4 0'- e o B O ~, dione .032 0.0 0.0 3.0 4.0 0.0 5.0 0.0 3.0 0.0 1.0 1.0 1.0009.09.0 B.O 9.0 B.0 a.o 9.09.0 2.0 7.0 9.0 4.0 3.0 7.0 1,9b~-Dihydro-3~-isopropyl- .500 9.09.0 B.0 B.0 7.0 8.0 9.0 2.0 7.0 9.0 2.0 2.0 3.0 3,7-dimethyl-5H-imidazo- .250 9.09.08.0 B.O 8.0 4.0 8.0 B.O 1.0 3.0 7.0 2.0 2.0 2.0 [1',2':1,2~pyrrolo[3,4--b]-- B O l O 2 0 3 0 0 0 6806010 7 0 2 0 pyridine-2(3H),5-dione .0320.0 4.0 0.0 0.0 0.0 0.0 4.0 2.0 1.0 2.0 3.0 1.0 0.0 1.0 1 0009.0 9.0 9.0 9.0 9.09.09.09.09.09.0 B.O 9.0 9.0 9.0 (R)-(+)-1,9b ~Dihydro-3 ~ 5009.09.09.09.09.09.09.09.09.09.08.09.09.09.0 isopropyl-3-methyl-5H- .250 9.0 9.0 9.0 9.08.09.08.09.08.09.08.0 ~.09.09.0 . . r I - .125 9.09.09.09.09.09.0 B.09.0 8.0 9.0 7.0 8.09.09.0 lmldazoLl',2 :1,2~pyrrolo-.0~3 B.O 9.08.09.08.09.0 8.0 9.08.0 8.0 ~.0 8.0 8.09.0 [3,4-b]pyridine-2(3H),5- .032 7.0 8.0 7.0 9.0 7.0 9.0 7.0 7.0 2.0 8.0 4.0 8.0 B.O 8.0 dione ~ C.
C~
c~

TA~LE V (Continued) POS~-E~IERBCIICE rESrS -- RA~ES 11~ KG/IIA
BA11llY FOX-A P llur QU~CK FLD 131!1!11CL RA5'1E \IELVE C~ l CO~O QICE. SO'~LE SO~'OE S UIIE
RATE AnDGR IL SP SEOGE GRASS IIIO~;D R~ Sl' CU- IL~Ar FlELO N IIATO All CR A'l ~I AT EH
Compound ---~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~ ~ ~~~~~ ~~~~~ ~~~~~
(+)--1,9b~--Dihydro--3~--iso-- ~ 9 ~ 9 ~ 9 ~ 9 o 9009090909090 propyl--3--methyl--5H--imidazo-- .2509.09.0 B.09.09.09.0 B.0 B.0 9.09.0 B.09.0 a.o 90 [1',2':1,2]pyrrolo[3,4--b]-- .125 B.0 9.0 ?.09.0 a.o 9.0 ?.0 B.09.08.o 5.o B.0 B.0 8 0 pyridine--2(3~1),5-dione 2 0 ? o 9030~ B 0 30 ? 040 1,9b~--Dihydro--3~--isopropyl-- 0 90 B 070 B 00 ? o B 0 B 090 3,8--dimethyl--51~--lmldaZO-- .2509.09.0 B.04.0 B.0 ?.0 B.0 3.0 5.0 8.0 9.0 3.03.0 3.0 [1',2':1,2]pyrrolo[3,4--b]-- .125 B.09.0 ?.04.0 5.0 2.0 ~.0 1.0 3.0 B.0 9.0 3.0 3.0 4.0 ~--.0~34.09.04.03.0 2.0 1.0 4.00.0 2.0 6.0 ?.0 2.0 2.0 20 --pyrlulne-~ cJlone .0320.04.00.00.00.00.0 2.0 0.0 2.02.04.02.02.020 8-(Allyloxy)-1,9b~-dihydro-3~-isopropyl-3-methyl-5H-imidazo[l',2':1,2]pyrrolo-[3,4-b]pyridine-2(3H),5_ dione 10009.0907.09.09.0909.09.0 ?.0 B.06.09.0 B.09.0 ,9b~-DihydrO-3o~1SOprOpyl- 50090' 9070909090909.o ?.0 B.0 ~.08.0 B.09.0 3-methyl-5H-imidazo- .250 9.09.04.09.09.09.0 B.0 ~1.07,0 B.0 5.0 8.0 8.0 9.0 [1' 2'-1 2~pyrrolo[3 IJ--b]-- .125 9.09.02.09.0 B.0 9.0 ~.0 B.07.0 ~.0 3.0 B.0 ?.09.0 . ' -- .0639.09.0 2.0 9.0 B.09.0 B.0 O.07.07.03.07.07.0 B.0, pyrldine-2(3ll) ,5--dlOne .032 l~.0 9.00.0 B.0 B.0 B.0 ~.0 B.03.07.0 2.0 7.06.0 B.0 C~

C~
;:~

TABLE V (Continued) POST-EMERGEIICE TESTS -- RATE~ Ill KG/HA
~ARIIY FOXTA P NUT ~UACK FLO B ~RIIGL RAGUE VELVE CORII COT~O RICE SO~BE SOr~E S WHE
~lTE ARDGR IL SP SEDGE GRAS~ IIID~:O RY SP ED TLEAF FIEEO N IIATO AN Bn AN ~I AT ER
. Compound ------- ----- ----- ~~~~- ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~ ~~~~~
7-Ethyl-1,9b~(and ~)-dihydro-I 0OO 9 o 9 o 4 o ~ o 9 o 5 5 B.5 8.0 0.5 1.0 6.0 0.0 0.0 2 0 3~-isopropyl-3-methyl-5H- soo 9.0 9.0 1.5 8.0 9.0 4.0 8.0 3.5 0.5 2.0 6.0 0.0 0.0 1.0 imidazo[l',2':1,2]pyrrolo-.250 B.5 7.0 0.0 2.0 6.0 3.0 5.0 3.0 0.5 1.0 6.0 0.0 0.0 1.0 [3 4-b]pyridine-2(31J) 5- .125 5.5- 4.0 0.0 2.0 2.0 2.0 2.0 1.5 0.5 0.0 4.0 0.0 0.0 0.0 -- -- ' .0~3 1.5 1.0 0.0 2.0 1.0 0.0 0.0 0.0 0.5 0.0 3.0 0.0 0.0 o.o ~ dione .032 1.0 0.0 0.0 2.0 1.0 0.0 0.0 0.0 0.5 0.0 2.0 0.0- 0.0 0.0 1 000 8.0 9 0 8.0 8 0 9.0 8.0 8.0 2.0 2.0 7.0 8.0 4.0 4.0 2.0 1,9b~-Dihydro-3 ~ isopropyl- 500 8.0 7 0 7.0 ~ 0 6.0 7.0 ~.0 0.0 2.0 5.0 7.0 3.0 3.0 2.0 8-methoxy-3-methyl-5H- .250 4.0 5.0 7.0 2.0 5.0 7.0 2.0 0.0 1.0 2.0 6.0 3.0 2.0 0.0 ~--imidazo[l',2':1,2~pyrrolo- l o l o o o 2 0 3 0~ o o ~ ~ 1 0 2 0 5 o 3 [3,4-b]pyridlne-2(3H),5- 032 1.0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 1.0 2.0 2.0 1.0 0.0 dione 1.000 ~.0 4.0 2.0 0.0 0.0 2.0 , 0.0 0.0 6.0 4.0 0.0 0.0 0.0 .500 2.0 2.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 ~.0 2.0 0.0 0.0 0.0 1,9b~-Dihydro-3~-isopropyl- .250 1.0 2.0 0.0 0.0 0.0 0.0 0.0 0.0 4.0 0.0 0.0 0.0 0.0 . . 125 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 3.0 0.0 0.0 0.0 0.0 3-methy~ -lmldaZO- 06,3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0 O O
[1',2':1,2~pyrrolo[3,4-b]- .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 2.0 0.0 0.0 0.0 0.0 quinoline-2(3H),5-dione -- 1.000 4.0 9.0 7.0 9.0 4.0 7.0 9.0 4.0 2.0 4.0 5.0 3.0 3.0 5.0 .500 2.0 B.0 3.0 6.0 1.0 5.0 8.0 2.0 2.0 2.0 4.0 2.0 2.0 4.0 8-Chloro-l,9~-dihydro- .250 1.0 ~.0 3.0 6.0 1.0 3.0 8.0 0.0 1.0 1.0 2.0 1.0 2.0 2.0 .125 0.0 6.0 1.0 2.0 0.0 1.0 7.0 0.0 0.0 0.0 1.0 1.0 1.0 1.0 3(~-lSOprOpyl-3-methyl- 0~3 0 0 0 0 0 0 1.0 0.0 0.0 4.0 0.0 0.0 0.0 1.0 0.0 0.0 0.0 5H-imidazo~1',2':1,2]- .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.0 0.0 0.0 pyrroloL3,11-b]pyridine- C~
2(3H),5-dione C~

C~

133931~

Preemergence herbicidal evaluation of test compounds The preemergence herbicidal activity of the compounds of the present invention is exemplified by the following tests in which the seeds of a variety of monocotyledonous and dicotyledonous plants are separ2-tely mixed with potting soil and planted on top of approximately one inch of soil in separ2te pint cups.
After planting, the cups are sprayed with the selected aqueous acetone solution containing test compound in sufficient quantity to provide the equiv21ent of about 0.016 to 10.0 kg per hectare of test compound per cup.
The treated cups are then placed on greenhouse benches, wat-red and cared for in accordar.ce with conventional greenhouse procedures. From four to five weeks after treatment, the tests are terminated and e2ch cup is ex2mined and rated according to the rating system set forth 2bove. The herbicidal proficiency of the active ingredients of the present invention is evident from the test results which are recorded in Table ~I below.
Where more than one test is involved for a given com-pound, the data are averaged.

TA~IE VI
PRE-E~lERGE~ICE TESTg ~- RATES I~l KG~HA
8ARrlr FOXTA P NUT nllACI~ FLD B~lRl~GL RAG~IE VELVECOR~I COTTO RICE~ SOY~3E S~YBE S ~HE
RATEARDGR IL SP SEOGE GnASS IIID~O RY SR E~ TLEAFFIELD 9~ ~IATO A\J E~R A~l III AT ER
_______ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____ 10.000B.0 8.0 B.0 8.0 8.0 Compound 1.000 3.0 6.0 8.0 7.0 8.0 0.0 3.0 5.0 0.0 3 ~ Ethyl-1,9b~(and l~)-di- ~500 ~-~ ~-~ 8.0 6.0 7.0 0.0 0.0 3.0 0.0 hydro-3-methyl-5H-imidazo- 125 0 0 0 0 0 0 0 0 5 0 0 0 0 0 0 0 0 0 [1',2':1,2]pyrrolo[3,4-b]- 0~3 0 0 0 0 0 0 0 0 0.0 0.0 0.0 0.0 0.0 pyridine-2t3H),5-dione .032 o.a o.o o.o o.o o.o o.o o.o o.o o.o 8.000 9.0 9.0 9.0 B.O 8.0 2 000 9 0 9 0 9 0 9.0 9.0 8.0 9.0 9.0 8.0 9.0 8.0 8.0 9.0 1,9b~(and ~)-dihydro-3~- l ooo 9 0 9 0 9 0 9.0 8.0 8.0 9.0 9.0 8.0 9.0 B.07.09.0 isopropyl-3-methyl-5H- .500 8.0 9.0 9.0 9.0 8.5 8.5 B.5 7.5 8.5 9.0 8.0 a.o 9.0 imidazo[l',2':1,2]pyrrolo-.250 8.0 8.0 8.0 9.0 8.5 8.0 8.5 6.5 7.5 8.0 7.0 6.5 8.0 r I -~ . . .125 7.0 5.5 7.0 9.0 8.5 6.5 8.5 3.5 6.0 7.5 5.0 5.5 7.0 L3,~1-b~pyrldlne-2(3~1),5- .06~ 3.0 2.5 4.0 8.5 5.5 3.0 8.0 2.0 2.5 4.5 2.0 2.5 5.0 dione .0~2 1.0 1.0 2.0 6.0 0.5 1.0 5.5 0.0 3.5 2.0 0.0 0.0 3.0 .016 0.0 0.~0 9.0 0.0 0.0 4.0 0.0 3 0 3.0 0.0 0.0 1,9b~-Dihydro-3~-isopropyl-1.000 9.0 9.0 9.0 9.0 8.0 9.99.0 3,7-dimethyl-511-imidazo- ~750 9.0 9.0 8.0 9.09.09.0 9.0 [1',2':1,2]pyrrolo[3,4-b]- 9 0 8 0 8 5 8 5 8 0 8 5 90 4 0 8 0 9 0 9 pyridine-2(311),5-dione .125 8.5 9.0 7.5 4.0 9.0 4.0 8.0 e.s 2.0 4.0 8.0 2.0 2.0 5.0 .0~3 8.0 6.0 3.0 4.0 7.0 1.0 8.0 3.0 2.0 3.0 6.0 2.0 7.0 2.0 .032 3.0 4.0 2.0 2.0 ~.0 0.0 2.0 1.0 2.0 2.0 2.0 2.0 ".O 1.0 (R)-(+)-1,9b~-Dihydro-3f3- .01~ o.o o.o 1.0 2.0 0.0 0.0 0.0 0.0 2.0 2.0 2.0 2.0 2.0 1.0 isopropyl-3-methyl-5~1-. . r ~ -- .500 9.0 9.0 9.09.09.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.n 9.0 lmldaZOLl~,2~ :1,2Jpyrrolo- .250 9.0 9.09.09.0 9.0 9.0 9.0 9.0 9.0 9.0 17.0 ~.0 B.O 9.0 [3,4-b]pyridine-2(311),5- .125 9.0 9.09.09.09.09.09.09.09.09.09.0 8.0 7.0 9.0 di -- .063 8.0 9.0 8.0 9.0 7.0 9.0 8.0 8.0 9.0 9.0 ~.0 7.0 7.0 9.0 one .032 3.0 9.0 7.0 9.0 7.0 8.0 3.0 7.0 7.0 7.0 5.0 6.0 4.0 9.0 .016 0.0 4.0 3.0 8.0 ~.0 7.0 0.0 7.0 2.0 2.0 4.0 3.0 3.0 7.0 e~ ~

TABLE VI (Continued) 8Aal~Y F~XTA P IIUr ~UACK FLO ~ ?11GL ~AGIIE VLLVE COnll .COTTO ~rCE. S~IBE CO~E S ~IIIE
~ATE ~.RDGR lL SP SEOGE GnA55 IIIL~WO llr s~- ED TLEAF FIElO ~ A~O All ~R All III A~ ER
_______ _____ _____ _____ _____ _____ _____ _ ___ _____ _____ _____ _____ _____ _____ _____ Compound (+)-1 9b~-Dihydro-3~-iso- .5009.09.09.09.09.09.09.09.09.09.09.09.0 B.09.0 - ' . . .2509.09.07.09.09.09.09.09.09.09.09.0 B.O B.O 9.0 prOpyl-3-methyl-5H-lmldaZO- .125 B.O 9.09.09.09.09.0 B.O 9.09.09.0 ~.00.07.09.0 [1',2':1,2]pyrrolo[3,4--b]-- .063 B.O 9.07.0 B.09.08.07.08.07.00.0 4.0 3.0 6.0 8.0 pyridine-2(31l),5-dione .032 3.0 B.0 4.0 8.09.00.0 3.0 9.05.0 4.0 3.0 7.0 2.0 7.0 .016 0.0 q.O 2.07.08.02.02.0 6.0 3.0 3.0 2.07.02.07.o 1,9bl3-Dihydro-3~-isopropyl- 90 90 90909 o 7 0 9080 3 0 909020 3,8-dimethyl-5H-imidazo- .1250.09.0 B.O 9.0 û.0 7.0 ~.0 7.04.0 5.0 6.0 2.02.00.0 [1' ,2~ :1,2]pyrrolo[3,11-b]- .063 0.0 7.0 6.0 7.0 5.0 4.0 0.0 5.0 3.0 4.0 4.01.02.0 3.0 ~--pyridine-2(3H),5-dione .032 0.0 4.04.03.0 5.0 0.0 3.03.02.0 2.0 3.0 1.0 2.0 2.0 ~~
8-(Allyloxy)-1,9b~-dihydro-3~-isopropyl-3-methyl-5H-imidazo[l',2':1,2]~?yrrolo- ~52~50 1 0 o o 3-0 2-0 1;0 2 0 2 0 0-0 0 ~ ~ ~ ~ ~ 1 0 o.o o o [3,4-b]pyridine-2(3H),5-dione 5009.09.09.09.09.09-o 9-o 9-09-09-08-09.0 B.09.0 1,9b~-Dihydro-3(x-isopropyl- 250 9.09.07.09.09.09.09.09.09.09.07.09.08.09.0 3-methyl-5H-imidazo- .o635 9-09-0 6-0 0-0 90 ~ 0 ~ o 90900 ~ ~3 0 4 0 4 0 0 0 ,~
[1~,2~:1,2~pyrrolo[3,11-b]- 032 708020707.00.00.09.0 3.0 3.0 3.0 5.0 2.07.0 pyridine-2(3H),5-dione016 207000 7 0 7.0 7.0 7.0 7.0 2.0 2.0 2.0 2.07.0 C~
c~n TABL~ VI (Continued) PI~E-EMERGEIICE TESrS -- RATES IN t~G~HA
t3ARtlY FOX~ P ~IUT QUACK FLD ~3 ~1RtlGL RAGIIE ~/ELVE COR~I COTTO RICE SOr~E ~)Y~E S ~IHE
R~TE ARnGRIL SP SEOGE GRASS IIIDIID RY SP EO TLEAF FIElO N NATO ~ T E~
7-Ethyl-1,9b~(and ~)-dihydro- l.ooo 9.0 B.O 9.0 9.0 9.0 9.0 9.0 3 ~ isopropyl--3-methyl--5~i--~500 B.5 9~0 B.O 9.0 9.0 7.5 9.0 7.5 3.0 4.0 9.0 0.0 1.07.0 imidazo[l' 2'-1 2]pyrrolo- .250 7.0 9.0 5.5 B.O B.5 2.5 7.0 7.0 2.0 2.0 9.0 0.~ ).02.0 .125 ~.0 9.0 3.0 5.0 B.O 0.5 4.5 4.0 2.0 0.0 6.0 0.0 0.00.0 [3~4~bJpyridine-2(3H)~5- .Ot~3 2.0 1!~.0 0.5 2.0 5.0 0.0 0.0 0.0 1.0 0.0 3.0 0.0 0.00.0 dione .032 0.0 2.0 0.0 0.0 0.0 0.0 0.0 1.0 0.0 2.0 0.0 0.00.0 .ol~ o.o a.o o.o o.o o.o o.o o.o o.o l.o o.o 2.0 0.0 0.00.0 1,9b ~Dihydro-30~isopropyl- .500 9.0 9.0 9.0 9.0 9.0 9.0 9.0 7.0 7.0 B.O t.O 5.0 4.07.0 8--methoxy--3--methyl--51i--.250 B.O 9.0 ~.0 7.0 7.0 B.O 8.0 4.0 5.0 B.O 4.0 3.07.0 -- .125 8.0 6.0 7.0 7.0 B.O 7.0 5.0 2.0 3.0 5.0 3.0 1.0 1.05.0 ~
imidazo[l',2':1,2]pyrrolo- .0~3 2.0 1!~.0 4.0 2.0 6.0 ~.0 2.0 1.0 3.0 2.0 2.0 0.0 1.02.0 w [3,4-b]pyridine-2(3H),5- .032 0.0 0.0 1.0 0.0 3.0 3.0 0.0 0.0 2.0 2.0 2.0 0.0 0.01.0 dione .ol~ o.o o.o o.o o.o o.o o.o o.o o.o 2.0 2.0 1.0 0.0 0.01.0 .500 B.O 5.0 6.0 0.0 4.0 0.0 r.o 4.0 0.0 0.0 0.0 0.0 0.00.0 1,9b ~Dihydro-3 ~ isopropyl- 250 7 0 5 0 2 0 0 0 3 0 0 0 7 0 3 0 o 0 0 0 0 0 0 0 0 00 o 3-methyl-5H-imidazo- .0~3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 ~.~ ~-~ ~-~ ~-~ ~-~ ~-~ ~-~
[1',2':1,2~pyrrolo[3,4-b]- .032 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00.0 quinoline-2(3i-l),5-dione .ol~ o.o o.o o.o o.o o.o o.o o.o o.o o.o o.o o.o o.o o.o o.o .500 7.0 9~0 9.0 9.0 9.0 7.0 9.0 5.0 ~.0 2.0 4.0 0.0 1.0 9.0 8-Chloro-l,9 ~dihydro- 4 0 ~ 0 7 0 4 0 5 0 B O 2 ~ 3 0 1 0 2 0 0 0 3 ~ isopropyl-3-methyl-.0~3 0.0 1.0 2.0 7.0 0.0 2.0 3.0 0.0 2.0 0.0 1.0 0.0 0.0 4.0 5H-imidazo[l',2'-1,2]- .032 0.0 0.0 1.0 ~.0 0.0 1.0 0.0 0.0 1.0 0.0 1.0 0.0 0.0 2.0 - -- r I ~ . . .Olt~ 0 0 0 0 0.0 3.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.0 0.0 2.0 C.l:) pyrroloL3,~-bJpyrldlne- ~ ~ C~
2(3H),5-dione cS~
c~

TA~LE VI ~Continued) PRE-E~IERGEIICE TESTS -- RATES I~l KG~IA
~ BARllr FOXTA P NUt qlJACK FLD El ~IQIIGL RAGIIE VELVE CORN COTTO RICE SOY13E SOYaE S I~IIE
RATE AROGR IL SP SEDGE GRASS IIIO~ID RY SP EO TLEAF FIELO ~l ~IATO ArJ I~R Al~ ~II AT ER
7-Ethyl-1,9b~-dihydro-3~- .500 9.0 9.0 8.0 2.0 9.0 7.0 9.0 t~.0 3.0 2.0 9.0 0.0 0.0 ~.0 isopropyl-3-methyl-5H-.250 9.0 9.0 7.0 1.0 9.0 7.0 7.0 ~1.0 2.0 1.0 9.0 0.0 0.0 8.0 imidazo~l',2':1,2]pyrrolo- ~ 1 O ~ O 4 0 0 0 42 o 63 o 1 0 0 0 7 0 -[3,4-b]pyridine-2(3H),5- .032 2.0 3.0 0.0 0.0 1.0 0.0 0.0 1.0 0.0 0.0 2.0 0.0 0.0 0.0 dione ~01~ ~-~ ~-~ ~-~ ~.o o.o o.o o.o o.o o.o o.o 2.q 0.0 0.0 0.0 .500 9.0 9.0 7.0 0.0 7.0 8.0 9.0 ~.0 2.0 9.0 0.0 2.0 B.0 7-Ethyl-1,9b~-dihydro-.250 9.0 9.0 ~.0 0.0 ~.0 7.0 9.0 7.0 2.0 2.0 7.0 0.0 1.0 3.0 , _ , 1.125 9.0 9.0 3.0 0.0 4.0 2.0 4.0 3.0 2.0 1.0 7.0 0.0 0.0 1.0 o~
sopropyl-~-rnetrlyl- .063 4.0 6.0 1.0 0.0 1.0 0.0 2.0 0.0 1.0 0.0 ~.o 0.0 0.0 0.0 5H-imidazo[1',2':1,2]- .032 1.0 2.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.0 3.0 0.0 0.0 0.0 pyrrolo[3,4-b]pyridine- .016 0.0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.0 2.0 0.0 0.0 0.0 2(3H),5-dione 500 9 o 9 o 9 o 9 o 9 o ~ o 7 o ,250 7.0 0.0 9.0 9.a 9.0 ~.0 ~.0 9.0 7.0 8.0 7.0 7.0 9.0 .125 ~.0 ~.0 ~.0 7.0 7.0 6.0 2.0 7.0 9.0 3.0 ~.0 5.0 4.0 9.0 ,9b,~-DlhydrO-3~1SO-Ot~3 1.0 2.0 2.0 7.0 6.0 2.0 1.0 ~.0 ~.0 1.0 2.0 3.0 2.0 4.0 propyl-3-methyl-2-thio-.032 0.0 1.0 0.0 2.0 0.0 0.0 0.0 3.0 3.0 0.0 1.0 1.0 1.0 2.0 5H-imidazo[1',2':1,2]- .ol~ o.o o.o . o.o o.o o.o o.o o.o 1.0 l.o o.o o.o o.o o.o o.o pyrrolo[3,4-b]pyridine-2(31~),5-dione :;~
c~

Claims (8)

1. A compound having the structure:

wherein R1 and R2 each represent C1-C3 alkyl or cyclopropyl, with the proviso that the sum of the number of carbon atoms in R1 and R2 is 2 to 5; and when R1 and R2 are taken together with the carbon to which they are attached, they may form a C3-C6 cycloalkyl ring optionally substituted with methyl;
X is hydrogen, halogen or methyl;
Y and Z are each hydrogen, halogen, C1-C6 alkyl, C1-C4 hydroxyalkyl, C1-C6 alkoxy, C1-C4 alkylthio, phenoxy, C1-C4 haloalkyl, OCF2CHF2, OCF3, OCHF2, nitro, cyano, NR4R5, C3-C8 straight or branched alkenyloxy optionally substituted with one to three halogens, C3-C8 straight or branched alkynyloxy optionally substituted with one to three halogens, or phenyl optionally substituted with one C1-C4 alkyl, C1-C4 alkoxy or halogen;
R4 is hydrogen or C1-C4 alkyl;
R5 is C1-C4 alkyl;
and, when taken together, Y and Z may form a ring in which YZ is represented by (1) the structure: -(CH2)n-, where n is an integer of 2, 3 or 4, provided that X is hydrogen; or (2) by the structure: where L, M, R7 and R8 each represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C1-C4 haloalkyl, NO2, CN, phenyl, phenoxy, amino, OCF3, OCHF2, OCF2CHF2, C1-C4 alkylamino, dialkyl(C1-C4)amino, chlorophenyl, methylphenyl, C3-C8 straight or branched alkenyloxy optionally substituted with one to three halogens, C3-C8 straight or branched alkynyloxy optionally substituted with one to three halogens, or phenoxy substituted with one Cl, CF3, NO2 or CH3 group, with the proviso that only one of L, M, R7 or R8 may represent a substituent other than hydrogen, halogen, C1-C4 alkyl or C1-C4 alkoxy; or (3) by the structures:
, , , or ;
where B is oxygen or sulfur; R9 and R10 each represent hydrogen, halogen, phenyl, or C1-C4 alkyl; R11 and R12 each represent hydrogen, C1-C4 alkyl or phenyl;
or when R1 and R2 are not the same, an optical isomer thereof.

2. A compound having the structure:

wherein R1 and R2 each represent C1-C3 alkyl or cyclopropyl, with the proviso that the sum of the number of carbon atoms in R1 and R2 is 2 to 5; and when R1 and R2 are taken together with the carbon to which they are attached, they may form a C3-C6 cycloalkyl ring optionally substituted with methyl;
X is hydrogen, halogen or methyl;
Y and Z are each hydrogen, halogen, C1-C6 alkyl, C1-C4 hydroxyalkyl, C1-C6 alkoxy, C1-C4 alkylthio, phenoxy, C1-C4 haloalkyl, OCF2CHF2, OCF3, OCHF2, nitro, cyano, NR4R5, C3-C8 straight or branched alkenyloxy optionally substituted with one to three halogens, C3-C8 straight or branched alkynyloxy optionally substituted with one to three halogens or phenyl optionally substituted with one C1-C4 alkyl, C1-C4 alkoxy or halogen;
R4 is hydrogen or C1-C4 alkyl;
R5 is C1-C4 alkyl;
and, when taken together, Y and Z may form a ring in which YZ is represented by (1) the structure: -(CH2)n-, where n is an integer of 2, 3 or 4, provided that X is hydrogen; or (2) by the structure: where L, M, R7 and R8 each represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C1-C4 haloalkyl, NO2, CN, phenyl, phenoxy, amino, OCF3, OCHF2, OCF2CHF2, C1-C4 alkylamino, dialkyl(C1-C4)amino, chlorophenyl, methylphenyl, C3-C8 straight or branched alkenyloxy optionally substituted with one to three halogens, C3-C8 straight or branched alkynyloxy optionally substituted with one to three halogens, or phenoxy substituted with one Cl, CF3, NO2 or CH3 group, with the proviso that only one of L, M, R7 or R8 may represent a substituent other than hydrogen, halogen, C1-C4 alkyl or C1-C4 alkoxy; or (3) by the structures: , , or <IGM> ; where B is oxygen or sulfur; R9 and R10 each represent hydrogen, halogen, phenyl or C1-C4 alkyl; R11 and R12 each represent hydrogen, C1-C4 alkyl or phenyl;
or when R1 and R2 are not the same, an optical isomer thereof.

3. A compound according to claim 1 or 2, wherein R1, R2 and X are as defined in claim 1 or 2, Y and Z each independently represent hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, CN, NO2, OCF3, OCHF2, OCF2CHF2, phenoxy, C1-C4 haloalkyl, C1-C4 alkylthio, C1-C4 hydroxyalkyl, NR4R5, C3-C8 alkenyloxy, C3-C8 alkenyloxy substituted with one to three halogens, C3-C8 alkynyloxy, C3-C8 alkynyloxy substituted with one to three halogens, phenyl, phenyl substituted with one C1-C4 alkyl, C1-C4 alkoxy or halogen; R4 is hydrogen or C1-C4 alkyl; R5 is C1-C4 alkyl; or Y and Z when taken together form a ring in which YZ is represented by the structure -(CH2)n- when n is an integer of 2, 3 or 4.

. -188-

4. A compound according to claim 1 or 2 of the formula wherein R1, R2 and X are as defined in claim 1 or 2; L, M, R7 and R8 represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C1-C4 haloalkyl, NO2, CN, phenyl, phenoxy, amino, CF3, OCHF2, OCF2CHF2, C1-C4 alkylamino, dialkyl(C1-C4)amino, chlorophenyl, methylphenyl, C3-C8 alkenyloxy, C3-C8 alkenyloxy substituted with one to three halogens, C3-C8 alkynyloxy, C3-C8 alkynyloxy substituted with one to three halogens or phenoxy substituted with one Cl, CF3, NO2 or CH3 group, with the proviso that only one of L, M, R7 or R8 may represent a substituent other than hydrogen, halogen, C1-C4 alkyl or C1-C4 alkoxy.

5. A compound according to claim 1 or 2 of the formula or wherein R1, R2 and B are as defined in claim 1 or 2, R9 and R10 each represent hydrogen, halogen, C1-C4 alkyl or phenyl, R11 and R12 each represent hydrogen, C1-C4 alkyl or phenyl.

6. A compound according to claim 1 or 2 of the formula or wherein R1, R2 and B are as defined in claim 1 or 2, R9 and R10 each represent hydrogen, halogen, C1-C4 alkyl or phenyl, R11 and R12 each represent hydrogen, C1-C4 alkyl or phenyl.

7. A compound according to claim 1 or 2, wherein R1 and R2 each represent methyl, ethyl, isopropyl, isobutyl or cyclopropyl or R1 and R2 together with the carbon to which they are attached represent cyclopentyl or methylcyclopentyl, X represents hydrogen, bromo, chloro or methyl, Y and Z
each represent hydrogen, bromo, chloro, methyl, ethyl, n-propyl, isopropyl, n-butyl, methoxy, methylthio, phenoxy, trifluoromethyl, difluoromethoxy, dimethylamino, allyloxy, propargyloxy, phenyl, methylphenyl or chlorophenyl, or Y and Z together represent -CH=CH-CH=CH-, -(CH2)3-, -(CH2)5-, -CH=CH-S- or -CH=CH-O-.

8. A compound according to claim 1 or 2, wherein R1 and R2 each represent methyl, ethyl or isopropyl, X represents hydrogen, Y and Z each represent hydrogen, chloro, methyl, ethyl, methoxy or allyloxy.