反应详情

In a RBF, tert-butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate (1.46 g, 2.43 mmol) was dissolved in DCM (4.86 ml, 2.43 mmol). TFA (749 μl, 9.72 mmol) was added at RT. The reaction was stirred at RT. After 20 min, LCMS showed mainly starting material. 1 mL of TFA was added and the reaction was allowed to stir at RT overnight. After 16 h, the reaction was concentrated and the residue dissolved in DCM. The solution was cooled to 0° C. and neutralized with 2N NaOH. At pH=5-7, the product as a white solid precipitated out. At pH>7, the product dissolves in DCM. The precipitate was filtered with aid of DCM. The solid product was set aside, while the filtrate was concentrated. The residue was diluted with a bit of DCM. Water was added. Ether was added and the whole solution was triturated to precipitate out additional product. The solid was filtered off with an aid of Et2O. This crop was combined with the first crop of solid. The product was purified by column chromatography on 120 g silica gel using 70:30 DCM:(90:10:1 DCM:MeOH:NH4OH). Fractions containing the product were combined, and concentrated, to afford an off white solid, which was triturated in Et2O. The resulting yellow solid was filtered off with an aid of Et2O and air dried. The solids were purified further via RPLC on the acidic Gilson Only fractions containing the product were combined, diluted with DCM, and washed with sat. NaHCO3. The organic was dried over MgSO4, filtered, and concentrated to afford N-(4-(3-(2-amino-5-fluoropyrimidin-4-yl)pyridin-2-yloxy)phenyl)4-phenylphthalazin-1-amine. MS Calcd for C29H20FN7O: [M]+=501. Found: [M+1]+=502.

1. stirringto stir at RT overnight
2. waitAfter 16 h
3. concentrationthe reaction was concentrated
4. dissolutionthe residue dissolved in DCM
5. temperatureThe solution was cooled to 0° C. and neutralized with 2N NaOH
6. customAt pH=5-7, the product as a white solid precipitated out
7. dissolutionAt pH>7, the product dissolves in DCM
8. filtrationThe precipitate was filtered with aid of DCM
9. concentrationwas concentrated
10. additionThe residue was diluted with a bit of DCM
11. additionWater was added
12. additionEther was added
13. customthe whole solution was triturated
14. customto precipitate out additional product
15. filtrationThe solid was filtered off with an aid of Et2O
16. customThe product was purified by column chromatography on 120 g silica gel using 70:30 DCM
17. additionFractions containing the product
18. concentrationconcentrated
19. customto afford an off white solid, which
20. customwas triturated in Et2O
21. filtrationThe resulting yellow solid was filtered off with an aid of Et2O and air
22. customdried
23. customThe solids were purified further via RPLC on the acidic Gilson Only fractions
24. additioncontaining the product
25. additiondiluted with DCM
26. washwashed with sat. NaHCO3
27. dry with materialThe organic was dried over MgSO4
28. filtrationfiltered
29. concentrationconcentrated