反应详情

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.70 mL, 0.53 mmol) was added to a solution of 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (200 mg, 0.48 mmol) in DCM (6 mL) and stirred at RT for 2 hours. 2-Amino-4-methylthiazole (110 mg, 0.96 mmol) and pyridine (0.078 mL, 0.96 mmol) were added and the reaction stirred at RT for 16 hours. The solvent was removed in vacuo, water (20 mL) added and the mixture extracted with ethyl acetate (3×20 mL). The extracts were combined and washed with 2N hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate solution (20 mL), water (20 mL), brine (20 mL), dried (MgSO4), filtered, and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (78 mg).

1. stirringthe reaction stirred at RT for 16 hours
2. customThe solvent was removed in vacuo, water (20 mL)
3. additionadded
4. extractionthe mixture extracted with ethyl acetate (3×20 mL)
5. washwashed with 2N hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate solution (20 mL), water (20 mL), brine (20 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue was chromatographed on silica
10. washeluting with a gradient of 50-100% ethyl acetate in isohexane