反应详情

To diethyl methylsulfonylmethylphosphonate (746 mg, 3.24 mmol) in THF (20 mL) at 0° C. was added potassium t-butoxide (1.0 M in THF, 3.25 mL, 3.25 mmol) and the mixture was stirred for 5 min. Then (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 3 (375 mg, 1.08 mmol) was added and the mixture was stirred at rt for 4 h. The mixture was treated with 1 N HCl and the resulting mixture was extracted with EtOAc. The organic layer was washed with brine and then concentrated to a residue (700 mg), which was subjected to silica gel chromatography eluting with 1-10% MeOH/DCM to give impure material. To a portion of this material (166 mg) in EtOAc (5 mL) was added 10% Pd—C (166 mg) and the mixture was stirred under a hydrogen atmosphere at rt overnight. The mixture was filtered and to the filtrate was added palladium on carbon (10%). The mixture was stirred under a hydrogen atmosphere for several hours, and then filtered. The filtrate was concentrated to a solid, which was triturated with ether to afford 2-(1-(4-fluorophenyl)-2-(methylsulfonyl)ethyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (22 mg). 1H NMR (300 MHz, DMSO-d6) δ 2.28 (s, 3H) 2.87 (s, 3H) 3.85 (m, 1H) 4.34 (m, 1H) 4.68 (bs, 1H) 6.45 (s, 1H) 7.15 (t, 2H) 7.49 (m, 3H) 7.76 (m, 2H) 8.56 (d, 1H) 10.36 (s, 1H) 12.17 (s, 1H); LC-MS (ESI) m/z 426 (M+H)+.

1. stirringthe mixture was stirred at rt for 4 h
2. extractionthe resulting mixture was extracted with EtOAc
3. washThe organic layer was washed with brine
4. concentrationconcentrated to a residue (700 mg), which
5. washeluting with 1-10% MeOH/DCM
6. customto give impure material
7. stirringthe mixture was stirred under a hydrogen atmosphere at rt overnight
8. filtrationThe mixture was filtered and to the filtrate
9. additionwas added palladium on carbon (10%)
10. stirringThe mixture was stirred under a hydrogen atmosphere for several hours
11. filtrationfiltered
12. concentrationThe filtrate was concentrated to a solid, which
13. customwas triturated with ether