Patent GB-1165025-A (GB)
Title: Hydrogenated Benzopyrano[3,4-d]-Pyridines, and Processes for the Preparation thereof
IPC: C07D491/04
Filed: 1966-09-16
Abstract: 1,165,025. Benzopyranopyridine derivatives. STERLING DRUG Inc. 16 Sept., 1966 [27 Sept., 1965], No. 41571/66. Heading C2C. The invention comprises compounds of the Formula I wherein R 1  represents an C 1-6  alkyl radical; R 2  represents an alkyl or cycloalkyl -C 1-4  alkyl radical; R 3  represents a hydrogen atom or a C 1-6  alkanoyl, cycloalkyl-C 1-4  alkyl, cycloalkyl-C 1-4  alkanoyl, C 3-7  alkenyl, C 3-7  alkynyl, halo-C 3-7  alkenyl, phenyl-C 1-4  alkyl, phenyl-C 1-4 -alkanoyl, phenyl-C 3-7  alkenyl or phenyl-C 3 - 7  alkynyl radical and R 4  represents a hydrogen atom or a C 1-6  alkyl, C 1-6  alkanoyl, carbamyl, N-(C 1-6  alkyl)-carbamyl or N,N-di- (C 1-6  alkyl) carbamyl radical or OR 4  represents a phosphate ester group and their acid addition and quaternary ammonium salts, and the preparation of a compound of said formula by debenzylating with hydrogen, in the presence of a catalyst a compound of the Formula I wherein R 3  represents a benzyl radical to give a compound of the Formula I wherein R 3  represents a hydrogen atom and R 1 , R 2  and R 4  are as defined above, and, if desired, reacting said compound with the appropriate hydrocarbon halide in the presence of an acid acceptor or acid halide or anhydride to give a compound of the Formula I where R 3  has one of the meanings defined above other than hydrogen and, if desired, reducing with an alkali metal aluminium hydride a compound of the Formula I wherein R 3  represents a cycloalkyl C 1-4  alkanoyl or phenyl-C 1-4  alkanoyl radical and R 4  represents a hydrogen atom or C 1-6  alkyl radical to give a compound wherein R 3  is cycloalkyl-C 1-4  alkyl or phenyl-C 1-4  alkyl radical and, if desired reacting a compound of the Formula I wherein R 4  represents a hydrogen atom with a C 1-6  alkyl halide in the presence of an acid acceptor to give a compound where R 4  represents a C 1-6  alkyl radical and, if desired reacting a compound of the Formula I wherein R 4  represents a hydrogen atom with a C 1-6  alkanoic anhydride, to give a compound of the Formula I wherein R 4  represents C 1-6  alkanoyl radical and if desired, reacting a compound of the Formula I wherein R 4  represents a hydrogen atom with a molar equivalent of phosgene and reacting the resulting chloroformatic with ammonia or a C 1-6  alkylamine or di-(C 1-6  alkyl) amine to give a compound of the Formula I wherein R 4  represents a carbamyl, alkyl- or dialkyl-carbamyl group respectively and, if desired reacting a compound of the Formula I wherein R 4  represents a hydrogen atom with a molar equivalent of phosphorus oxychloride and reacting the resulting dichlorophosphinate with aqueous sodium or potassium carbonate to give a compound of the Formula I wherein R 4  represents a phosphonyl radical, and, if desired converting any resulting compound into an acid addition or quaternary ammonium salt thereof. The compounds of the Formula I wherein R 3  represents a benzyl radical may be prepared by reacting a ketone of the Formula II with a C 1-6  alkylmagnesium halide. Ketones of the Formula II wherein R 3  represents a benzyl radical may be prepared by reacting a compound of the Formula III with a compound of the Formula IV A resorcinol of the Formula IV may be prepared by dehydrating a 3,5-di-(C 1-6  alkoxyphenyl alkyl (or cycloalkyl-C 1-6  alkyl) carbinol, reducing the resulting alkene and cleaning the ether groups of the resulting diether. The carbinols referred to above being suitably prepared by reacting an appropriate Grignard reagent with a 3,5-di-(C 1-6  alkoxybenzoic acid ester, anide or 3<SP>1</SP>,5<SP>1</SP>-di-(C 1-6  alkoxy) alkano-phenone (or 3<SP>1</SP>,5<SP>1</SP>-di-(C 1-6  alkoxy) alkanophenone. Cycloalkyl groups referred to above have 3 to 8 carbonatoms. Therapeutic compositions with central nervous system depressant activity comprise the compounds of the invention with appropriate carriers in forms suitable for oral or parenteral administration.