Claims
- 1. A process for preparing 2-carbamoyloxyalkyl-1,4-dihydropyridine derivative represented by the general formula: ##STR143## where R.sup.1 is halogen, cyano, nitro, hydroxyl, di-lower alkyl substituted amino or lower alkoxy, each of R.sup.2 and R.sup.3 is lower alkyl, .beta.-chloroethyl, .beta.-bromoethyl, .beta.-chloropropyl, .gamma.-chloropropyl, .omega.-chlorobutyl, .beta.,.beta.-dichloroethyl, trifluoromethyl, .beta.,.beta.,.beta.-trichloroethyl, lower alkenyl, lower alkynyl, phenyl, benzyl, hydroxyalkyl, lower alkoxyalkyl, lower alkenyloxyalkyl, .beta.-benzyloxyethyl, .beta.-phenylethyloxyethyl, .beta.-(.alpha.-methylbenzyloxy)ethyl, .beta.-phenoxyethyl, .beta.-pyridyloxyethyl, .beta.-phenoxypropyl, .beta.-phenoxybutyl or ##STR144## (where B is straight-chained or branched C.sub.2-4 alkylene, and each of R.sup.7 and R.sup.8 is lower alkyl, benzyl or phenyl, or R.sup.7 and R.sup.8 form, together with the adjacent nitrogen atom, a heterocyclic group), R.sup.4 is hydrogen or lower alkyl, A is C.sub.1-8 alkylene, and each of R.sup.5 and R.sup.6 is hydrogen, lower alkyl, .beta.-chloroethyl, .beta.-bromoethyl, .beta.-chloropropyl, .gamma.-chloropropyl, .omega.-chlorobutyl, .beta.,.beta.-dichloroethyl, trifluoromethyl, .beta.,.beta.,.beta.-trichloroethyl, hydroxyalkyl, cycloalkyl, benzyl or phenyl, or R.sup.5 and R.sup.6 form, together with the adjacent nitrogen atom, a heterocyclic group, which comprises:
- (a) reacting under cooling, at room temperature, or under warming or heating a 3-amino-3-carbamoyloxyalkylacrylic acid derivative represented by the general formula: ##STR145## where R.sup.3, R.sup.5, R.sup.6 and A are as defined above, with a benzylidene compound represented by the general formula: ##STR146## where R.sup.1, R.sup.2 and R.sup.4 are as defined above in water, an inert organic solvent, or a mixture thereof; or
- (b) reacting under cooling, or at room temperature, or under warming or heating the 3-amino-3-carbamoyloxyalkylacrylic acid derivative of the general formula II with an aldehyde compound represented by the general formula: ##STR147## wherein R.sup.1 is as defined above, and a .beta.-keto-ester compound represented by the general formula:
- R.sup.4 --CO--CH.sub.2 --COOR.sup.2 (V)
- where R.sup.2 and R.sup.4 are as defined above in water, an inert organic solvent, or a mixture thereof; or
- (c) reacting under cooling, or at room temperature, or under warming or heating a 3-carbamoyloxyalkylpropiolic acid derivative represented by the general formula:' ##STR148## where R.sup.3, R.sup.5, R.sup.6 and A are as defined above, with the benzylidene compound of the general formula II and ammonia or its salt in water, an inert organic solvent, or a mixture thereof; or
- (d) reacting under cooling, or at room temperature, or under warming or heating the 3-carbamoyloxyalkylpropiolic acid derivative of the general formula VI with the aldehyde compound of the general formula IV, the .beta.-keto-ester compound of the general formula V and ammonia or its salt in water, an inert organic solvent, or a mixture thereof.
- 2. The process according to claim 1, wherein a 3-amino-3-carbamoyloxyalkylacrylic acid derivative of the general formula II where R.sup.5 is hydrogen and R.sup.6 is hydrogen, lower alkyl, cycloalkyl, aralkyl or aryl, is reacted with the benzylidene compound of the general formula III to obtain a 2-carbamoyloxyalkyl-1,4-dihydropyridine derivative of the general formula I where R.sup.5 is hydrogen and R.sup.6 is hydrogen, lower alkyl, cycloalkyl, aralkyl or aryl.
- 3. The process according to claim 1, wherein a 3-carbamoyloxyalkylpropiolic acid derivative of the general formula VI where R.sup.5 is hydrogen and R.sup.6 is hydrogen, lower alkyl, cycloalkyl, aralkyl or aryl, is reacted with the benzylidene compound of the general formula III and ammonia or its salt to obtain a 2-carbamoyloxyalkyl-1,4-dihydropyridine derivative of the general formula I where R.sup.5 is hydrogen and R.sup.6 is hydrogen, lower alkyl, cycloalkyl, aralkyl or aryl.
- 4. The process according to claim 1, wherein R.sup.1 is fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, dimethylamino, diethylamino, dipropylamino, methoxy, ethoxy, propoxy or butoxy; each of R.sup.2 and R.sup.3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, .beta.-chloroethyl, .beta.-bromoethyl, .beta.-chloropropyl, .gamma.-chloropropyl, .omega.-chlorobutyl, .beta.,.beta.-dichloroethyl, trifluoromethyl, .beta.,.beta.,.beta.-trichloroethyl, vinyl, allyl, 3-butenyl, isopropenyl, propargyl, 2-butynyl, benzyl, .alpha.-methylbenzyl, phenethyl, phenyl, pyridyl, naphthyl, quinonyl, .beta.-hydroxyethyl, .beta.-hydroxypropyl, .beta.-hydroxybutyl, .gamma.-hydroxypropyl, .omega.-hydroxybutyl, .beta.,.gamma.-dihydroxypropyl, .beta.-methoxyethyl, .beta.-ethoxyethyl, .beta.-propoxyethyl, .beta.-isopropoxyethyl, .beta.-butoxyethyl, .beta.-isobutoxyethyl, .beta.-tertiarybutoxyethyl, .beta.-methoxypropyl, .beta.-ethoxypropyl, .beta.-propoxypropyl, .beta.-isopropoxypropyl, .beta.-butoxypropyl, .gamma.-methoxypropyl, .gamma.-ethoxypropyl, .gamma.-propoxypropyl, .gamma.-butoxypropyl, .omega.-propoxybutyl, .beta.-vinyloxyethyl, .beta.-allyloxyethyl, .beta.-(3-butenyloxy)ethyl, .beta.-isopropenyloxyethyl, .beta.-allyloxypropyl, .beta.-benzyloxyethyl, .beta.-phenethyloxyethyl, .beta.-(.alpha.-methylbenzyloxy)ethyl, .beta.-phenoxyethyl, .beta.-pyridyloxyethyl, .beta.-phenoxypropyl, .beta.-phenoxybutyl, .beta.-dimethylaminoethyl, .beta.-diethylaminoethyl, .beta.-methylethylaminoethyl, .beta.-dimethylaminopropyl, .gamma.-dimethylaminopropyl, .omega.-dimethylaminobutyl, .beta.-N-methylbenzylaminoethyl, .beta.-N-methylbenzylaminopropyl, .beta.-N-methylbenzylaminobutyl, .gamma.-N-methylbenzylaminopropyl, .omega.-N-methylbenzylaminobutyl, .beta.-piperidinoethyl, .beta.-(4-methylpiperazino)ethyl, .beta.-(4-ethylpiperazino)ethyl, .beta.-(4-propylpiperazino)ethyl, .beta.-(4-methylhomopiperazino)ethyl, .beta.-morpholinoethyl, .gamma.-morpholinopropyl, .omega.-morpholinobutyl, .beta.-homomorpholinoethyl, .beta.-(1-pyrrolidinyl)ethyl, .beta.-(1-imidazolidinyl)ethyl, .beta.-(1-imidazolinyl)ethyl, .beta.-(1-pyrazolidinyl)ethyl, .beta.-(1-indolinyl)ethyl, .beta.-(2-isoindolinyl)ethyl or .beta.-N-methylanilinoethyl; R.sup.4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tertiary butyl; A is methylene, ethylene, trimethylene or tetramethylene; and each of R.sup.5 and R.sup.6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiarybutyl, .beta.-chloroethyl, .beta.-bromoethyl, .beta.-chloropropyl, .gamma.-chloropropyl, .omega.-chlorobutyl, .beta.,.beta.-dichloroethyl, .beta.,.beta.,.beta.-trichloroethyl, trifluoromethyl, .beta.-hydroxyethyl, .beta.-hydroxypropyl, .gamma.-hydroxypropyl, .omega.-hydroxybutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl, .alpha.-methylbenzyl, phenethyl, phenyl, pyridyl or naphthyl, or R.sup.5 and R.sup.6 form, together with the adjacent nitrogen atom, a heterocyclic group selected from the group consisting of piperidino, 4-methylpiperazino, 4-ethylpiperazino, 4-propylpiperazino, 4-methylhomopiperazino, morpholino, homomorpholino, 1-pyrrolidinyl, 1-imidazolidinyl, 1-imidazolinyl, 1-pyrazolidinyl, 1-indolinyl and 2-isoindolinyl.
- 5. The process according to claim 1, wherein R.sup.1 is o-nitro, m-nitro, o-chloro, o-cyano or o-methoxy, each of R.sup.2 and R.sup.3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, .beta.-chloroethyl, allyl, propargyl, benzyl, phenyl, .beta.-methoxyethyl, .beta.-ethoxyethyl, .beta.-propoxyethyl, .beta.-isopropoxyethyl, .beta.-allyloxyethyl, .beta.-benzyloxyethyl, .beta.-phnoxyethyl, .beta.-N-methylbenzylaminoethyl, .beta.-piperidinoethyl, .beta.-(4-methylpiperazino)ethyl or .beta.-morpholinoethyl, R.sup.4 is methyl or ethyl, A is methylene or ethylene, R.sup.5 is hydrogen and R.sup.6 is hydrogen, methyl, ethyl, propyl, cyclohexyl, phenyl, p-chlorophenyl or m,p-dichlorophenyl.
Priority Claims (3)
Number |
Date |
Country |
Kind |
57-136343 |
Aug 1982 |
JPX |
|
57-151706 |
Sep 1982 |
JPX |
|
57-177647 |
Oct 1982 |
JPX |
|
Parent Case Info
This is a division, of application Ser. No. 863,984, filed May 16, 1986, now U.S. Pat. No. 4,914,227, which is a divisional of application Ser. No. 517,844 filed Jul. 27, 1983 now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4686217 |
Baxter et al. |
Aug 1987 |
|
Divisions (2)
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Number |
Date |
Country |
Parent |
863984 |
May 1986 |
|
Parent |
517844 |
Jul 1983 |
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