Patent GB-582254-A (GB)
Title: Quinoline substituted dihydropyridines
IPC: C07D401/04
Filed: 1944-05-15
Abstract: Alkyl, ester and quinoline substituted dihydropyridines having the general formula <FORM:0582254/IV/1> wherein R and R1 represent alkyl radicals containing from 1 to 5 carbon atoms, R1 not representing a methyl group unless the group represented by R contains either one or from three to five carbon atoms or R2 represents an alkyl group, and R2 represents a residue selected from hydrogen and the alkyl radicals containing from 1 to 5 carbon atoms, are obtained by heating quinoline-4-aldehyde with an alkyl ester of a b -amino or b -alkyl-amino a -b -unsaturated aliphatic acid having either one or from 3 to 5 carbon atoms in each alkyl group and from 4 to 8 carbon atoms in the acyl group, or having 1 to 5 carbon atoms in each alkyl group and from 5 to 8 carbon atoms in the acyl group, or of a b -alkylamino-2 : b -unsaturated aliphatic acid having from 1 to 5 carbon atoms in each alkyl group and from 4 to 8 carbon atoms in the acyl group.  Alternatively, the quinoline-4-aldehyde is heated with a mixture of one of the alkyl esters of an unsaturated aliphatic acid specified above with an alkyl ester of a b -keto aliphatic acid containing in the ester-fuming alkyl group and in the acyl group the same number of carbon atoms as the specified alkyl ester of the unsaturated acid. Or, the quinoline-4-aldehyde is heated with a mixture of an alkyl ester of a b -keto aliphatic acid having either one or from 3 to 5 carbon atoms in the alkyl group and from 4 to 8 carbon atoms in the acyl group, and ammonia.  Or, the quinoline-4-aldehyde is heated with a mixture of an alkyl ester of a b -keto aliphatic acid having from 1 to 5 carbon atoms in the alkyl group and from 5 to 8 carbon atoms in the acyl group and ammonia. Or, the quinoline-4-aldehyde is heated with a mixture of an alkyl ester of a b -keto aliphatic acid having from 1 to 5 carbon atoms in the alkyl group and from 4 to 8 carbon atoms in the acyl group with a primary alkyl amine containing from 1 to 5 carbon atoms.  In each case, the product may be converted into its acid addition salt by treatment with a non-oxidizing and non-toxic salt forming acid. Specified acids are: hydrochloric, hydrohoxic, phosphoric, boric, acetic, citric and lactic.  In examples quinoline-4- aldehyde is heated for at least 6 hours at 90 to 120 DEG  C. with - (1) methyl - b  - ethyl - b  - amino - acrylate (prepared by treating propionyl acetic acid methyl ester with ammonia), and the cooled reaction product is dissolved in alcohol from which the product is precipitated by adding water; (2) propyl - b  - butyl - b  - methyl amino acrylate and propyl valeryl acetate; (3) ethyl butyryl acetate and ethylamine; (4) ethyl - b  - amyl - b  - propylamino - acrylate and ethyl caproyl acetate; the product being isolated in examples 2 to 4 as in 1.  Specification 567,009 is referred to.  The Provisional Specification describes also the preparation of compounds of the above general formula but restricted in range only by the proviso that R and R1 represent alkyl radicals containing from 1 to 5 carbon atoms (which may be the same or different) and R2 represents either hydrogen or an alkyl radical containing from 1 to 5 carbon atoms.  In examples 1 to 3 it discloses the preparation of diethyl g  - quinolyl - 1 : 4 - dihydro - a  : a 1 - butidine - b .b 1-dicarboxylic esters.