反应详情

温度

0 °C

A mixture of cis-4-[4-chloro-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]-2,6-dimethylmorpholine (100 mg, 0.314 mmol) and copper (I) iodide (11.95 mg, 0.063 mmol) in tetrahydrofuran (1 ml) was stirred at 0° C. under argon and isobutyl magnesium chloride (2M solution in tetrahydrofuran) (0.314 ml, 0.627 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 90 minutes. Saturated ammonium chloride solution was added and the mixture was extracted with ethyl acetate. The organic extract was separated, washed with saturated ammonium chloride solution, water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 50-100% ethyl acetate in isohexanes. The product (61 mg, 0.18 mmol) was dissolved in dichloromethane (1 ml) and methanol (0.5 ml) and hydrogen chloride (1M in ether, 0.2 ml) was added. The solvent was evaporated and the residue was co-evaporated with ether. The residue was triturated with ether and the resulting solid was collected and dried to give the title compound (48 mg, 41%). LC/MS [M+H]+=341. 1H NMR (400 MHz, d6-DMSO): δ 8.74 (1H, d), 8.36 (1H, s), 7.87-7.85 (1H, m), 7.81-7.78 (1H, m), 4.62-4.58 (2H, m), 3.61-3.54 (2H, m), 2.72 (3H, s), 2.63-2.58 (4H, m), 2.15-2.08 (1H, m), 1.18 (6H, d), 0.79 (6H, d).

1. stirringThe reaction mixture was stirred at 0° C. for 90 minutes
2. extractionthe mixture was extracted with ethyl acetate
3. extractionThe organic extract
4. customwas separated
5. washwashed with saturated ammonium chloride solution, water and brine
6. customdried
7. customevaporated
8. customThe residue was purified by silica gel chromatography
9. washeluting with 50-100% ethyl acetate in isohexanes
10. customThe solvent was evaporated
11. customThe residue was triturated with ether
12. customthe resulting solid was collected
13. customdried