反应详情

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.16 mL, 1.2 mmol) was added to a solution of 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-(1-methyl-2-oxo-pyrrolidin-3-yl)oxy-benzoic acid (Intermediate 10) (288 mg, 0.68 mmol) in DCM (5 mL) and stirred at ambient temperature for 30 minutes. 4-Methyl-1,3-thiazol-2-amine (156 mg, 1.36 mmol) and pyridine (0.11 mL, 1.4 mmol) were added and the reaction stirred for 16 hours. The solvent was evaporated under reduced pressure. The residue dissolved in ethyl acetate (30 mL), washed with water (2×10 mL) and brine (10 mL), dried (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 0-5% methanol in DCM, to afford the product (117 mg, 34%). 1H NMR δ (300 MHz, CDCl3) 2.10-2.26 (m, 4H), 2.38 (quintet, 2H), 2.50-2.63 (m, 1H), 2.93 (s, 3H), 3.33-3.56 (m, 2H), 4.26 (t, 2H), 4.69 (t, 2H), 4.84 (t, 1H), 6.54 (s, 1H), 7.15 (s, 1H), 7.36 (s, 1H), 7.53 (s, 1H), 8.32 (s, 1H), 8.82 (s, 1H), 10.43 (s, 1H); m/z 509 (M+H)+

1. stirringthe reaction stirred for 16 hours
2. customThe solvent was evaporated under reduced pressure
3. dissolutionThe residue dissolved in ethyl acetate (30 mL)
4. washwashed with water (2×10 mL) and brine (10 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated under reduced pressure
8. customThe residue was purified by flash chromatography on silica
9. washeluting with a gradient of 0-5% methanol in DCM