Hydrochloric Acid → HCID 10448320, compound

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (251 mg, 0.82 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (146 mg, 0.82 mmol). This solution was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (150 mg, 0.63 mmol). This solution was stirred at 0° C. for 15 min and then was allowed to warm to 25° C. where it was stirred for 30 min. The reaction was then treated with 2-amino-4,5-dimethylthiazole hydrochloride (239 mg, 1.45 mmol) and was stirred at 25° C. for 30 min. The reaction was then treated with N,N-diisopropylethylamine (0.22 mL, 1.26 mmol) and stirred at 25° C. for 2 d. At this time, the reaction was diluted with water (30 mL) and ethyl acetate (30 mL). This mixture was treated with a 1N aqueous hydrochloric acid solution (10 mL). The organic layer was separated and was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid pyridin-2-ylamide (483 mg, 83%) as a yellow solid: mp 149-150° C.; (ES)+-HRMS m/e calcd for C17H16ClN3O (M+Na)+ 336.0874, found 336.0876.

Provenance & Evidence