反应详情

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.10 mL, 0.75 mmol) was added to a solution of the 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid (Intermediate 6) (265 mg, 0.62 mmol) in DCM (5 mL) and stirred at ambient temperature for 30 minutes, a further aliquot of 1-chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.10 mL) was added and stirring continued for a further 30 minutes. 4-Methyl-1,3-thiazol-2-amine (142 mg, 1.2 mmol) and pyridine (0.10 mL, 1.2 mmol) were added and the reaction stirred for 16 hours. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (15 mL) and DCM (15 mL), washed with water (2×10 mL) and brine (10 mL), dried (MgSO4), filtered and evaporated under reduced pressure to give the crude product which was purified by flash chromatography on silica, eluting with a gradient of 0-5% methanol in DCM, to afford the product (181 mg, 58%). 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. stirringstirring
2. waitcontinued for a further 30 minutes
3. stirringthe reaction stirred for 16 hours
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate (15 mL)
6. washDCM (15 mL), washed with water (2×10 mL) and brine (10 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated under reduced pressure
10. customto give the crude product which
11. customwas purified by flash chromatography on silica
12. washeluting with a gradient of 0-5% methanol in DCM