2-Aminothiazole → HCID 10470973, compound

Temperature

0 °C

A solution of triphenylphosphine (219 mg, 0.84 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (149 mg, 0.84 mmol). The reaction was stirred at 0° C. for 15 min. At this time, the reaction was treated with 1-isopropyl-6-methoxy-1H-indole-3-carboxylic acid (150 mg, 0.64 mmol). The reaction 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-aminothiazole (148 mg, 1.48 mmol) and stirred at 25° C. for 24 h. At this time, the mixture was partitioned between water (50 mL) and ethyl acetate (50 mL) and treated with a 1N aqueous hydrochloric acid solution (25 mL). The organic layer 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 then dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 1-isopropyl-6-methoxy-1H-indole-3-carboxylic acid thiazol-2-ylamide (101 mg, 50%) as tan solid: mp 182-185° C.; EI-HRMS m/e calcd for C16H17N3O2S (M+) 315.1041, found 315.1039.

1. stirringThe reaction was stirred at 0° C. for 5 min
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 30 min
4. stirringstirred at 25° C. for 24 h
5. customAt this time, the mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
6. additiontreated with a 1N aqueous hydrochloric acid solution (25 mL)
7. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL)
8. dry with materialThe organic layer was then dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-c2796885a86c4e958b5bce3f99eaa985

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2