反应详情

温度

80 °C

A mixture of (S)—N-[4-fluoro-2-(pyridin-2-ylamino)phenyl]-2-(9H-purin-6-ylamino)propionamide (130 mg, 0.332 mmol) in AcOH (1 mL) was heated for 2 h at 80° C. A second portion of (S)—N-[4-fluoro-2-(pyridin-2-ylamino)phenyl]-2-(9H-purin-6-ylamino)propionamide (136 mg, 0.347 mmol) in AcOH (5 mL) was heated for 2 h at 100° C. The two crude reaction mixtures were combined and the volatiles removed in vacuo. The resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) then triturated in MeOH/diethyl ether to afford 182 as an off-white solid (66 mg, 26%). LCMS (Method K): RT 2.94 min [M+H]+ 375.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.89 (1H, br s), 8.61 (1H, br s), 8.20-7.80 (4H, m), 7.79-7.67 (2H, m), 7.52-7.43 (1H, m), 7.20-7.08 (2H, m), 5.86 (1H, br s), 1.63 (3H, d, J=6.82 Hz)

1. customThe two crude reaction mixtures
2. customthe volatiles removed in vacuo
3. customThe resulting residue was partitioned between EtOAc
4. washThe organic layer was washed with water
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)
8. customthen triturated in MeOH/diethyl ether