Hydrochloric Acid → HCID 10019767, compound

Temperature

0 °C

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 5 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 5 min and then was allowed to warm to 25° C. where it was stirred for 30 min. The reaction was then treated with 4-methyl-thiazol-2-ylamine (166 mg, 1.45 mmol) and was stirred at 25° C. for 2 d. At this time, the reaction was diluted with water (25 mL) and ethyl acetate (25 mL) and 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 (1×20 mL) and a saturated aqueous sodium chloride solution (1×20 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 (4-methyl-thiazol-2-yl)-amide (50 mg, 24%) as a yellow solid: mp 201-203° C.; (ES)+-HRMS m/e calcd for C16H16ClN3OS (M+) 333.0703, found 333.0704.

1. stirringThis solution was stirred at 0° C. for 5 min
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 30 min
4. stirringwas stirred at 25° C. for 2 d
5. customThe organic layer was separated
6. washwas washed with a saturated aqueous sodium bicarbonate solution (1×20 mL)
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-a672fa94b0184736842c5dc035145cea

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2