反应详情

Heat a mixture of 5-chloro-2-(5-fluoro-3-methylpyridin-2-yl)-1,8-naphthyridine (81 mg, 0.3 mmol), 2-amino-5-trifluoromethylpyrimidine (96 mg, 0.6 mmol), xantphos (16.9 mg), Pd2(dba)3 (27.9 mg) and Cs2CO3 (193 mg) in dioxane (2.0 mL) at 100° C. for 4 hours. Cool the mixture, concentrate under vacuum, dilute with EtOAc/water (5.0 mL each), filter through celite, wash celite with EtOAc (2×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by preparative HPLC to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.92 (s, 1H), 9.0 (s, 2H), 8.92 (d, 1H, J=2.2 Hz), 8.58 (s, 1H), 8.17(d, 1H, J=1.1 Hz), 8.09 (m, 1H), 7.8 (d, 1H, J=2.4 Hz), 2.69 (s, 3H). MS=401.31 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.

1. temperatureHeat
2. temperatureCool the mixture
3. concentrationconcentrate under vacuum
4. additiondilute with EtOAc/water (5.0 mL each)
5. filtrationfilter through celite
6. washwash celite with EtOAc (2×5 mL)
7. customdry
8. filtrationFilter the dried
9. extractionextract
10. concentrationconcentrate under vacuum
11. customto afford crude product
12. customPurify by preparative HPLC