2H-Benzimidazol-2-one,5-chloro-1,3-dihydro-6-methyl-(9CI) synthesis

Yield:683240-81-5 80%

Reaction Conditions:

in tetrahydrofuran at 20; for 3 h;Inert atmosphere;

Steps:

49.a

Example 49: l-(5-chloro-l-cyclobutyl-6-methyl-lH-benzo[d]imidazol-2-yl)-7V-cyclopentyl- piperidine-4-carboxamide and l-(6-chloro-l-cyclobutyl-5-methyl-lH-benzo[d]imidazol-2- yl)-7V-cyclopentylpiperidine-4-carboxamide(a) Preparation of the intermediate compound 5-chloro-6-methyl-lH-benzo[d]imidazol-2(3Η)- one:To a stirred solution of 4-chloro-5-methylbenzene-l,2-diamine (0.3 g, 1.9 mmol) intetrahydrofuran (5 mL) was added JV,iV-carbonyl dimidazole (CDI, 0.465 g, 2.8 mmol). The reaction mixture was stirred at room temperature for 3 hours under Argon gas, concentrated in vacuo and the residue partitioned between ethyl acetate (50 mL) and aqueous sodium hydroxide (50 mL, IN). The aqueous extract was acidified to pH 5 via addition of aqueous hydrochloric acid (1.57V) and the resulting brown precipitate was filtered, washed with water (3^χ20mL) and dried under high vacuum to obtain 0.28 g (80 % yield) of 5-chloro-6-methyl-lH- benzo[d]imidazol-2(3H)-one.

References:

WO2011/23812,2011,A1 Location in patent:Page/Page column 95