反应详情

温度

-78 °C

To a solution of phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 38, 1 g, 2.116 mmol) and 6-amino-4-isopropoxynicotinonitrile (intermediate 97, 380 mg, 2.144 mmol) in THF (8 ml) at −78° C. was added LHMDS 1M in THF (4.3 ml, 4.30 mmol) and the reaction mixture was stirred at −78° C. for 2 h and 10 min. The reaction mixture was quenched by the addition of saturated aqueous NaH4CI and partitioned between ethyl acetate/hepatane (1:1) and water. The organic layer was washed with water, the water layer was back extracted with ethyl acetate/hepatane (1:1) and the combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of ethyl acetate (0-20%) in heptane to yield the title compound as a white solid. (UPLC-MS 3) tR 1.69 min; ESI-MS 556.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 14.00 (s, 1H), 8.36 (s, 1H), 7.96 (s, 1H), 7.75 (s, 1H), 5.44 (d, 1H), 4.89-4.79 (m, 3H), 4.08-4.00 (m, 2H), 3.45 (s, 6H), 2.87 (t, 2H), 2.06-1.95 (m, 2H), 1.44 (d, 6H), 0.95 (s, 9H), 0.12 (d, 6H).

1. customThe reaction mixture was quenched by the addition of saturated aqueous NaH4CI
2. custompartitioned between ethyl acetate/hepatane (1:1) and water
3. washThe organic layer was washed with water
4. extractionthe water layer was back extracted with ethyl acetate/hepatane (1:1)
5. customthe combined organic layers were dried
6. filtrationfiltered
7. customevaporated
8. customThe crude product was purified by silica gel column chromatography
9. washeluting with a gradient of ethyl acetate (0-20%) in heptane