反应详情

To a solution of (5-amino-pyridin-3-yl)-[7-bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-methanone (Preparation 287) (50 mg, 0.11 mmol) in THF (5 mL) at room temperature was added 5-fluoro pyridine-2-yl acetic acid (27 mg, 0.17 mmol), TEA (0.08 mL, 0.56 mmol) and 1-propylphosphonic acid cyclic anhydride (50% solution in EtOAc, 0.20 mL, 0.34 mmol). The resulting mixture was before stirred for 18 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between saturated sodium bicarbonate solution (10 mL) and ethyl acetate (25 mL). The organic phase was dried over sodium sulphate and concentrated under reduced pressure. TFA (1.5 mL) was added and the resulting mixture stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure and the residue partitioned between saturated sodium bicarbonate (10 mL) and ethyl acetate (30 mL). The organic phase was dried over sodium sulphate, concentrated under reduced pressure purified by Preparative TLC (MeOH:DCM 5:95) to afford the title compound as off white solid in 31% yield, 16 mg. 1H NMR (400 MHz, DMSO-d6) δ: 2.32 (s, 6H), 2.66 (s, 1H), 3.94 (s, 2H), 6.57 (s, 2H), 7.49 (m, 1H), 7.69-7.73 (m, 2H), 8.38 (s, 1H), 8.50 (d, 1H), 8.65 (d, 1H), 8.92 (s, 1H), 8.96 (d, 1H), 10.67 (s, 1H); LCMS (System 10): Rt=2.85 min; m/z 458 [M+H]+.

1. concentrationThe mixture was concentrated under reduced pressure
2. customthe residue was partitioned between saturated sodium bicarbonate solution (10 mL) and ethyl acetate (25 mL)
3. dry with materialThe organic phase was dried over sodium sulphate
4. concentrationconcentrated under reduced pressure
5. additionTFA (1.5 mL) was added
6. stirringthe resulting mixture stirred at room temperature for 18 hours
7. concentrationThe mixture was concentrated under reduced pressure
8. customthe residue partitioned between saturated sodium bicarbonate (10 mL) and ethyl acetate (30 mL)
9. dry with materialThe organic phase was dried over sodium sulphate
10. concentrationconcentrated under reduced pressure
11. custompurified by Preparative TLC (MeOH:DCM 5:95)