Abstract: The present invention relates to a method for preparation of alkyl 4-[5-[bis(2 -hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7) from 2-fluoro-5-nitroaniline, comprising the steps of: (a) conversion of 2-fluoro-5-nitroaniline to 5-(2-fluoro-5-nitroanilino)-5 -oxopentanoic acid (1) using glutaric anhydride, conversion of compound (1) to methylammonium 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoate (2) using methylamine; conversion of compound (2) to 5[2-(methylamino)-5-nitroanilino]-5-oxopentanoic acid (3) and condensation of compound (3) to 4-(1-methyl-5-nitro-1H-benzimidazol-2-yl)butanoic acid (4); (b) esterification of the product (4) of step a) to alkyl 4-(1-methyl-5-nitro 1H-benzimidazol-2-yl)butanoate (5); (c) reduction of the product of step b) to alkyl 4-(5-amino-l-methyl-1H-benzimidazol-2-yl)butanoate (6), and (d) conversion of the product of step c) to alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl -1H-benzimidazol-2-yl]butanoate (7).

Abstract: The present invention relates to a method for preparation of alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7) from 2-fluoro-5-nitroaniline, comprising the steps of: (a) conversion of 2-fluoro-5-nitroaniline to 5-(2-fluoro-5-nitroanilino)-5-oxopentanoic acid (1) using glutaric anhydride, conversion of compound (1) to methylammonium 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoate (2) using methylamine; conversion of compound (2) to 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoic acid (3) and condensation of compound (3) to 4-(1-methyl-5-nitro-1H-benzimidazol-2-yl)butanoic acid (4); (b) esterification of the product (4) of step a) to alkyl 4-(1-methyl-5-nitro1H-benzimidazol-2-yl)butanoate (5); (c) reduction of the product of step b) to alkyl 4-(5-amino-1-methyl-1H-benzimidazol-2-yl)butanoate (6), and (d) conversion of the product of step c) to alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7)

Abstract: A method for the synthesis of dienogest from 3-methoxy-estra-1,3,5-trien-17-one includes the steps of a) reacting 3-methoxy-estra-1,3,5-trien-17-one with alcohol in the presence of an acid in an organic solvent to form 3-methoxy-17,17-dialkoxy-estra-1,3,5-triene; b) subjecting the product of step a) to partial reduction by reaction with alkali metal in liquid ammonia; c) treating the product of step b) with mild acid; d) reacting the product of step c) with cyanomethyl lithium; e) treating the product of step d) with oxalic acid; and f) treating the product of step e) with pyridinium tribromide in pyridine to yield dienogest.

Abstract: A collagen preparation comprising collagen-I for human or veterinary medicine obtainable by proteolyzing, cross-linking, reducing, optionally heat treating, and finally sterilizing mammalian collagen I material under conservation of its biological texture.