2-Aminothiazole → HCID 9973267, compound

Temperature

0 °C

A solution of triphenylphosphine (179 mg, 0.68 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (122 mg, 0.68 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 (125 mg, 0.53 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-thiazole (121 mg, 1.21 mmol) and was stirred at 25° C. for 3 d. At this time, the reaction was partitioned between water (30 mL) and ethyl acetate (30 mL). The organic layer was separated and then washed with a 1N aqueous hydrochloric acid solution (1×20 mL), a saturated aqueous sodium bicarbonate solution (1×20 mL), water (1×20 mL), and a saturated aqueous sodium chloride solution (1×20 mL). The organic layer was then 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 thiazol-2-ylamide (62 mg, 37%) as a pink solid: mp 202-204° C.; EI-HRMS m/e calcd for C17H16ClN3O (M+) 319.0546, found 319.0547.

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 3 d
5. customAt this time, the reaction was partitioned between water (30 mL) and ethyl acetate (30 mL)
6. customThe organic layer was separated
7. washwashed with a 1N aqueous hydrochloric acid solution (1×20 mL)
8. dry with materialThe organic layer was then dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-22281167c1ab4db881cc3aa70ad29c72

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2