反应详情

温度

70 °C

To a stirred solution of methyl 6-((tert-butyldimethylsilyloxy)methyl)-2-methylpyrimidine-4-carboxylate (4.70 g, 15.86 mmol, Preparation #6) in MeOH (50 mL) were added DIEA (8.3 mL, 47.59 mmol Spectrochem) and 4-fluoro-3-methoxybenzylamine (3.8 g, 24.58 mmol, WO 2008/083056). The reaction mixture was heated to about 70° C. for about 15 h. The solvents were removed in vacuo and the crude material partitioned between EtOAc (300 mL) and 1N HCl solution (300 mL). The layers were separated and the aqueous layer extracted with EtOAc (1×150 mL). The combined organic layers were washed successively with 1N HCl solution (1×200 mL), water (1×200 mL) and brine (1×250 mL), dried over sodium sulphate and evaporated to dryness. The residue obtained was purified by silica gel (60-120 mesh) chromatography eluting with 25 to 35% of EtOAc in hexane. Relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford 6-((tert-butyldimethylsilyloxy)methyl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide 5.4 g (81%); 1H NMR (400 MHz, DMSO): δ 9.431-9.400 (t, J=6.0 Hz, 1H), 7.884 (s, 1H), 7.173-7.112 (m, 2H), 6.897-6.860 (m, 1H), 4.794 (s, 2H), 4.468-4.452 (d, J=6.4 Hz, 2H), 3.814 (s, 3H), 2.68 (s, 3H), 0.934 (s, 9H), 0.118 (s, 6H), MS m/z: 420 (M+H).

1. customThe solvents were removed in vacuo
2. customthe crude material partitioned between EtOAc (300 mL) and 1N HCl solution (300 mL)
3. customThe layers were separated
4. extractionthe aqueous layer extracted with EtOAc (1×150 mL)
5. washThe combined organic layers were washed successively with 1N HCl solution (1×200 mL), water (1×200 mL) and brine (1×250 mL)
6. dry with materialdried over sodium sulphate
7. customevaporated to dryness
8. customThe residue obtained
9. customwas purified by silica gel (60-120 mesh) chromatography
10. washeluting with 25 to 35% of EtOAc in hexane
11. additionRelevant fractions containing the target compound
12. customevaporated to dryness under reduced pressure