Patent GB-1444369-A (GB)
Title: 1,8-naphthyridines
IPC: C07D471/04
Filed: 1973-04-05
Abstract: 1444369 9 1,8-Naphthyridines ALLEN & HANBURYS Ltd 19 March 1974 [5 April 1973] 16278/73 Heading C2C [Also in Division A5] Novel 1,8-naphthyridines of the formula in which R 1  is H, halogen, alkenyl or alkyl, or OR 3  or NR 3 R 4 , where R 3  and R 4  each are H or alkenyl or an alkyl group optionally substituted by one or more OH, alkoxy, acyloxy aryl, amino, alkylamino, dialkylamino, diaralkylamino or alkylaralkylamino groups, or R 3  and R 4  together with the N atom form a 5- or 6- membered saturated heterocyclic ring that may optionally contain other hetero atoms, and R 2  has the same meanings as R 3 , and pharmaceutically acceptable salts thereof are prepared by reacting the appropriate 1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids or reactive derivatives thereof with 5-amino-1H-tetrazole. Compound of the above formula in which R 2  is hydroxyalkyl may be obtained by hydrolysing compounds of the above formula in which R 2  is acyloxyalkyl, those in which R 1  is OR 3 , by treating corresponding compounds in which R 1  is Cl with compounds of the formula R 3 OM, where M is an alkali metal atom, those in which R t  is NR 3 R 4  by reacting compound in which R 1  is halogen and compounds of the formula R 3 R 4 NH, and those in which R 2  is aminoalkyl or alkylaminoalkyl by the hydrogenolysis of compounds in which R 2  is dibenzylaminoalkyl or benzylalkylaminoalkyl. 1 - (2 - Dimethylaminoethyl)- 1,4 - dihydro - 7- methyl - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid hydrochloride is obtained by hydrolysing the corresponding ethyl ester, resulting from the reaction between 1,4-dihydro-7- methyl - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid allyl ester and 2-dimethylaminoethyl chloride hydrochloride 1-[2-(N-Benzyl-N- methylamino)ethyl - [or 1 - [2 - (dibenzylamino)ethyl]- or 1 - (2 - phenylethyl)- or 1- isopropyl-] - 1,4- dihydro - 7 - methyl - 4 - oxo- 1,8 - naphthyridine - 3 - carboxylic acids and their ethyl esters are prepared in a similar manner. 1 - (2 - Formyloxyethyl) - 1,4 - dihydro - 7- methyl - 4 - oxo - 1,8 - naphthyridine - 3 - carcoxylic acid is obtained by formylating the corresponding 1-(2-hydroxyethyl) compound. 7 - Ethoxy - 1 - (2 - formyloxyethyl) - 1,4 - dihydro - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid is prepared by formulating 7-ethoxy-1,4- dihydro - 1 - (2 - hydroxyethyl) - 4 - oxo - 1,8- naphthyridine-3-carboxylic acid, obtained by reacting 2-bromoethanol with 7-ethoxy-1,4-dihydro - 4 - oxo - 1,8 - naphthyridine - 3- carboxylic acid. 7 - Chloro - 1,4 - dihydro - 4 - oxo - 1,8 - naphthyridine-3-carboxylic acid is made by reacting 7 - hydroxy - 1,4 - dihydro - 4 - oxo - 1,8- naphthyridine with phosphoryl chloride. 7 - Chloro - 1 - ethyl - 1,4 - dihydro - 4 - oxo- 1,8 - naphthyridine-3-carbonyl chloride is prepared by reacting the corresponding acid with thionyl chloride. 1,4 - Dihydro - 1 - (2 - methoxyethyl) - 7- methyl - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid is obtained by etherifying 1,4-dihydro - 1 - (2 - hydroxyethyl) - 7 - methyl- 4 - oxo - 1,8 - naphthridine - 3 - carboxylic acid.