2-Aminothiazole → 3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-N-thiazol-2-yl-propionamide

温度

0 °C

A solution of triphenylphosphine (213 mg, 0.84 mmol) in methylene chloride (12 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (144 mg, 0.84 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with the 3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionic acid (150 mg, 0.4 mmol). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then treated with 2-aminothiazole (122 mg, 1.22 mmol), and the resulting suspension was stirred for 15 h at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (30 mL) and a 1N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/2 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-N-thiazol-2-yl-propionamide (128 mg, 70%) as an amorphous solid: EI-HRMS m/e calcd for C20H21F3N6OS (M+) 450.1449, found 450.1454.

1. stirringThe clear solution was stirred for 15 min at 0° C.
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 2 h
4. stirringthe resulting suspension was stirred for 15 h at 25° C
5. concentrationThe reaction mixture was then concentrated in vacuo
6. customto remove methylene chloride
7. additionthe residue was diluted with ethyl acetate (30 mL)
8. customThe two layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (1×20 mL)
10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
11. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORDレコード

ord-c16fd879952c4a1a87f55f90c70a24f8

出典データセット

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06441180B1