反应详情

温度

150 °C

4-Chloro-6-(2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethoxy)pyrimidin-2-amine (0.75 g, 1.89 mmol), L-p-boronophenylalanine (0.47 g, 2.26 mmol), Pd(PPh3)2Cl2 (79 mgs, 0.113 mmol), Na2CO3 (0.44 g, 4.15 mmol), acetonitrile (10 mls), and H2O (10 mls) were combined in a 20 ml microwave reactor and heated in the microwave at 150° C. for 7 minutes. The reaction was complete by LCMS (Sunfire, neutral). The mixture was concentrated, dissolved in NaOH (20 mls 0.5 N), filtered, extracted with ether three times, and cooled to 0° C. At 0° C., 1.0 N HCl was added slowly until a pH of 6.5 was attained. The mixture was stirred at 0° C. for 30 minutes and the product was filtered, dried in air, treated with excess 2.0 N HCl in ether, concentrated, then triturated with CH2Cl2 to give 1.12 g, 99% (95.5% purity). 385 mgs were purified via prep HPLC (Sunfire, TFA), concentrated, treated with excess 1.0 N HCl (aq.), concentrated to a small volume and lyophilized to afford 240 mgs of the captioned compound. M+1=527; 1H NMR δ (CD3OD) 7.86 (d, 2H), 7.64 (s, 4H), 7.49 (d, 2H), 7.36 (m, 2H), 7.28 (m, 1H), 7.02 (m, 1H), 6.95 (s, 1H), 6.75 (q, 1H), 4.26 (t, 1H), 3.32 (m, 1H), 3.21 (m, 1H).

1. concentrationThe mixture was concentrated
2. dissolutiondissolved in NaOH (20 mls 0.5 N)
3. filtrationfiltered
4. extractionextracted with ether three times
5. temperaturecooled to 0° C
6. additionAt 0° C., 1.0 N HCl was added slowly until a pH of 6.5
7. filtrationthe product was filtered
8. customdried in air
9. additiontreated with excess 2.0 N HCl in ether
10. concentrationconcentrated
11. customtriturated with CH2Cl2
12. customto give 1.12 g, 99% (95.5% purity)
13. custom385 mgs were purified via prep HPLC (Sunfire, TFA)
14. concentrationconcentrated
15. additiontreated with excess 1.0 N HCl (aq.)
16. concentrationconcentrated to a small volume