Patent GB-1092921-A (GB)
Title: Anthranilic acid derivatives
Filed: 1965-06-17
Abstract: The invention comprises compounds of the general formula <FORM:1092921/C2/1> (wherein R1 represents H, Me, Cl or NH2, R2 represents Me, Cl or NH2, and R3 represents Cl or <FORM:1092921/C2/2> wherein R4 and R5 are identical and each represent H, Me or Et, or jointly represent a tetramethylene group, one and only one of R1, R2 and R3 representing an amino group), their pharmaceutically acceptable carboxylate salts, their C1- 7 alkyl and di-(C1- 4 alkyl) -aminoalkyl esters, and the pharmaceutically acceptable acid addition and quaternary ammonium salts of the dialkylaminoalkyl esters, and the preparation thereof by the processes of the examples, which may be summarized as follows: (a) for compounds wherein R6 is Cl or NH2, reduction of the corresponding nitro compounds of the general formula <FORM:1092921/C2/3> (wherein R represents H, C1- 7 alkyl, di-(C1- 4 alkyl) aminoalkyl or a salt-forming cation, Z1 represents H, Me, Cl or NO2, Z2 represents Me Cl or NO2, and Z3 represents Cl or NO2, one of Z1, Z2 and Z3 being NO2); (b) for free acids, alkali metal salts and C1- 7 alkyl esters other than those in which R1 or R3 is NH2, condensing together compounds of the general formulae <FORM:1092921/C2/4> <FORM:1092921/C2/5> (wherein R7 and R8 correspond to R1 and R3 respectively except that neither is NH2, M represents H, C1- 7 alkyl or an alkali metal cation, and one of A and B is halogen and the other NH2); (c) for free acids, alkali metal salts and C1- 7 alkyl esters in which R3 is a tertiary amino group as defined, treating the corresponding compounds in which R3 is NH2 with alkylating agents or 1,4-dichlorobutane; (d) for free acids or alkali metal salts in which R3 is a tertiary amino group as defined, hydrolysis of compounds of the general formula <FORM:1092921/C2/6> (wherein R9 represents Me or Cl, R10 and R11 are identical and are Me and Et, or jointly form a tetramethylene group, R12 represents Me or Cl, and R13 represents COOH or a salt thereof or a group hydrolysable thereto; (e) for the salts and esters, reacting the free acids with appropriate inorganic or organic bases or esterifying agents, and, if desired, converting the dialkylaminoalkyl esters into acid addition or quaternary ammonium salts.  Alternative methods of preparation are described in general terms. Nitro compounds of the second general formula above are prepared by reacting potassium o-bromobenzoate with a 2-Z2-3-Z3-6-Z1-aniline and, if desired, converting the product into a salt or ester.  The preparation of the following starting materials and intermediates is also described: 6 - chloro - 3 - nitro - 2 - methylaniline; 4-bromo - 2,6 - dichloroacetanilide and its 3-nitro-derivative; 4 - bromo - 2,6 - dichloro - 3-nitroaniline; 3 - nitro - and 3 - amino - 2,6 - dichloroacetanilide; 2,6 - dichloro - 3 - dimethylaminoacetanilide; 2,6 - dichloro - 3 - dimethylaminoaniline; N - benzoyl - 2 - cyano - 21,61-dichloro - 31 - dimethylaminodiphenylamine; 4-bromo - 2,6 - dichloroanisole and its 3 - nitroderivative; 2,6 - dichloro - 3 - dimethylaminoanisole; 2,6 - dichloro - 3 - dimethylaminophenol; N - benzoyl - 2 - cyano - 21 - chloro - 31- dimethylamino - 61 - methyldiphenylamine; 2- chloro - 6 - methyl - 3 - nitroanisole; 2 - chloro- 3 - dimethylamino - 6 - methylanisole; and 2 - chloro - 3 - dimethylamino - 6 - methylphenol.