2-Aminothiazole → 1-isopropyl-6-methyl-1H-indole-3-carboxylic acid thiazol-2-ylamide

Temperature

0 °C

A solution of triphenylphosphine (628 mg, 2.39 mmol) in methylene chloride (5 mL) cooled to 0° C. was treated with N-bromosuccinimide (425 mg, 2.39 mmol). The reaction was stirred at 0° C. for 15 min and then was treated with 1-isopropyl-6-methyl-1H-indole-3-carboxylic acid (400 mg, 1.84 mmol). The reaction 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-aminothiazole (424 mg, 4.23 mmol) and stirred at 25° C. for 16 h. At this time, the mixture was partitioned between water (75 mL) and ethyl acetate (75 mL) and treated with a 1N aqueous hydrochloric acid solution (40 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×40 mL) and a saturated aqueous sodium chloride solution (1×40 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 hexanes/ethyl acetate) afforded 1-isopropyl-6-methyl-1H-indole-3-carboxylic acid thiazol-2-ylamide (229 mg, 41.5%) as a tan solid: mp 215-217° C.; EI-HRMS m/e calcd for C16H17N3OS (M+) 363.0041, found 363.0034.

1. stirringThe reaction was stirred at 0° C. for 15 min
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 30 min
4. stirringstirred at 25° C. for 16 h
5. customAt this time, the mixture was partitioned between water (75 mL) and ethyl acetate (75 mL)
6. additiontreated with a 1N aqueous hydrochloric acid solution (40 mL)
7. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×40 mL)
8. dry with materiala saturated aqueous sodium chloride solution (1×40 mL), dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-05363255424946e781ced7ea6d9e69a5

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2