反应详情

温度

85 °C

Under an argon atmosphere, 2,4-dichloro-5-fluoropyrimidine (390 mg, 2.34 mmol) and 2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-ylboronic acid (1.01 g, 2.34 mmol) were dissolved in 1,2-dimethoxyethane (15.6 ml, 2.34 mmol) in a screw capped test tube. Sodium carbonate (4.67 ml, 9.34 mmol) was added followed by Pd(PPh3)4 (0.270 g, 0.234 mmol). The tube was purged with argon, sealed, and heated to 85° C. After 3 h, LCMS showed mostly product, a small amount of starting material left. 100 mg of Dichlorofluoropyrimidine was added, and the reaction was stirred overnight. After 22 h, LCMS showed complete conversion to product. Water was added. The product was extracted with DCM. The organic phase was dried over MgSO4, filtered, and concentrated. Hexane was added to the residue. A tan solid precipitated and was filtered off with an aid of hexane. The product was purified using an ISCO column chromatography on silica gel eluting with 80:20 DCM:(90:10:1 DCM:MeOH:NHOH) and was obtained as a yellow solid, N-(4-(3-(2-chloro-5-fluoropyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine (1.13 g, 93% yield). MS Calcd for C29H18ClFN6O: [M]+=520. Found: [M+1]+=521.

1. customcapped test tube
2. customThe tube was purged with argon
3. customsealed
4. waita small amount of starting material left
5. addition100 mg of Dichlorofluoropyrimidine was added
6. waitAfter 22 h
7. additionWater was added
8. extractionThe product was extracted with DCM
9. dry with materialThe organic phase was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. additionHexane was added to the residue
13. customA tan solid precipitated
14. filtrationwas filtered off with an aid of hexane
15. customThe product was purified