Hydrochloric Acid → HCID 11742033, compound

Temperature

0 °C

A solution of triphenylphosphine (182 mg, 0.69 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (124 mg, 0.69 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 5 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-thiazol-4-yl)-acetic acid ethyl ester (294 mg, 1.58 mmol) and was stirred at 25° C. for 16 h. At this time, the reaction was diluted with water (50 mL) and ethyl acetate (50 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, 3/1 hexanes/ethyl acetate) afforded {2-[(6-chloro-1-isopropyl-1H-indole-3-carbonyl)-amino]-thiazol-4-yl}-acetic acid ethyl ester (62 mg, 24%) as an orange foam: mp 65-75° C.; (ES)+-HRMS m/e calcd for C19H20ClN3O3S (M+H)+ 406.0987, found 406.0986.

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 16 h
5. customThe organic layer was separated
6. washwas washed with a saturated aqueous sodium bicarbonate solution (1×25 mL)
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-9c5fd88bd2504fa892b2936b3b5764a1

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2