反应详情

To a solution of 2-amino-5-methylpyridine (203 mg, 1.88 mmol) in dichloromethane (5 mL) at 0° C. was added Al(CH3)2Cl (1.88 mL, 1M in hexanes) drop wise. After the addition, the ice-bath was removed, and the mixture was stirred for 30 minutes at room temperature. Ethyl 4-({1-[(dimethylamino)carbonyl]azetidin-3-yl}oxy)-2-methyl-1-benzofuran-6-carboxylate (65 mg, 0.19 mmol) was added and the stirring was continued for 14 h. The reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously. The product was extracted with CHCl3, washed with brine and dried over Na2SO4. The product was purified by gradient silica gel chromatography using CHCl3/MeOH (95/5 to 85/15) to give the title compound (70 mg, 90%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.15 (s, 3 H) 2.37 (s, 3 H) 2.78 (s, 6 H) 3.30-3.44 (m, 2 H) 3.44-3.60 (m, 1 H) 3.88 (dd, J=12.13, 6.06 Hz, 1 H) 4.05 (dd, J=11.75, 2.40 Hz, 1 H) 6.70 (s, 1 H) 6.98 (d, J=9.60 Hz, 1 H) 7.71-7.85 (m, 1 H) 7.92 (s, 1 H) 8.17 (d, J=8.34 Hz, 1 H) 8.28-8.44 (m, 2 H); MS (ESI, pos): 409.

1. additionAfter the addition
2. customthe ice-bath was removed
3. waitthe stirring was continued for 14 h
4. customThe reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously
5. extractionThe product was extracted with CHCl3
6. washwashed with brine
7. dry with materialdried over Na2SO4
8. customThe product was purified by gradient silica gel chromatography