TelMisartan DiMer IMpurity synthesis

Yield:-

Reaction Conditions:

Stage #1: C₄₈H₄₂N₄O₄with sodium hydroxide;water in N,N-dimethyl acetamide at 70 - 75; for 4 - 5 h;
Stage #2: with hydrogenchloride in water at 25 - 35; pH=4 - 5; for 0.5 - 0.75 h;

Steps:

20

EXAMPLE 20; PREPARATION OF 4'-[2-n-PROPYL-4- METHYL-6 {4"- (1-METHYL-BIPHENYL- 2^'-CARBOXYLIC ACID) BENZIMIDAZOL-2-YLJ-BENZIMIDAZOL-1-YL] - METHYL-BIPHENYL^-CARBOXYLIC ACID (FORMULA XVII); 3 g of the acid ester of Example 18 and 0.7 g of sodium hydroxide were charged into a round bottom flask containing 45 ml of water. The contents were heated to 70-75° C and stirred for 4-5 hours. Reaction completion was confirmed by thin layer chromatography and the mass was cooled to 25-35° C. Reaction mass pH was adjusted to 4-5 with 36% aqueous hydrochloric acid (3 ml) and stirred for 30-45 minutes. Filtered the solid and washed with 15 ml of water. Dried the solid at 50-55° C for 4-5 hours to get 2.0 g of the title compound.

References:

WO2006/44754,2006,A2 Location in patent:Page/Page column 38