FORFARANDE FOR FRAMSTELLNING AV BENSIMIDAZOL- ELLER IMIDAZO(4,5-B)PYRIDINFORENINGAR

1377469 Benzimidazoles and imidazo-(4,5-b)- pyridines ELI LILLY & CO 23 Dec 1971 [28 Dec 1970] 38302/73 Divided out of 1374800 Heading C2C A process for preparing benzimidazole or imidazo-(4,5-b)pyridine compounds of general formulµ wherein R1 is H, Cl, F, C 1-6 -pernuoroalkyl or a radical -(CHZ) n -CH 2 Z in which Z is H or halogen and n is 0 or 1; each R3 is halogen; each R4 is nitro, -CF 3 , -CF 2 Cl or -CF 2 H; R5 is cyano or C 1-4 alkylsulphonyl; m is 0 or an integer 1-3, n is 0, 1 or 2 and r is 0 or 1 and the sum of m, n and r is 0 or an integer of 1-3; R6 is halogen, nitro, -CF 3 , -CF 2 Cl, -CF 2 H or C 1-4 alkylsulphonyl provided that not more than one R6 is nitro, -CF 3 , -CF 2 Cl, -CF 2 H or alkylsulphonyl, involves treating an ester of a 1-hydroxybenzimidazole or imidazo(4,5-b) pyridine of general formula in which -OR2 is a group derived by reaction of the corresponding 1-hydroxy compound with a bromide, iodide, oxybromide, oxyiodide, oxide or sulphide of P, As or Sb or bromide, iodide, oxybromide or oxide of sulphur or R2 is (1) C 2-16 alkanoyl; (2) C 3-16 alkenoyl, (3) carbamoyl of formula -C(X)-N(R7) 2 wherein X is 0 or 5 one R7 is phenyl, C 1-4 alkyl or C 2-4 alkenyl and the other R7 is H, C 1-4 alkyl or C 2-4 alkenyl, providing both R7 taken together do not have more than 6C atoms, or both R7 taken together represent a C 2-6 straight alkylene chain; (4) a radical wherein R8 is methylene, ethylene or vinylene and q is 0 or 1, (5) -SO 2 -R9 in which R9 is C 1-4 alkyl, C 5-6 cycloalkyl, phenyl or benzyl or (6) -C(O)-X-C 1-4 alkyl or wherein X is O or S, with a bromide or iodide nucleophilic reagent, except that when -OR2 is a derivative of the 1-hydroxy compound and a sulphide the nucleophilic reagent is a sulphide. The Br or I ion may be provided by the compound used to derive the unstable halides or oxyhalides. Amongst the examples 6-chloro-2- (trifluoromethyl) - 1H - imidazo(4,5-b) - pyridine is obtained by treating the 1-hydroxy derivative with either P 2 S 5 or thionyl bromide, or by treating the 1-(methyl-sulphonyloxy) -compound with sodium iodide. 1 - Hydroxy - 6 - chloro - 2 - (trifluoromethyl)- 1H - imidazo(4,5-b) - pyridine is obtained by reductive cyclization of 5-chloro-3-nitro-2-(trifluoroacetamido)pyridine. Reference has been directed by the Comptroller to Specification 1,307,489.