反应详情

Heat a mixture of 6-(5-chloro-1,8-naphthyridin-2-yl)-5-(trifluoromethyl)pyridin-3-amine (64.8 mg, 0.2 mmol) and 2-amino-5-trifluoromethylpyridine (64 mg, 0.4 mmol) at 180° C. for 2.0 hours. Cool the mixture, dilute with EtOAc/1.0 N aq. NaOH (5.0 mL each), and separate the organic layer. Extract the aqueous layer with EtOAc (3×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify the crude product by HPLC to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.15 (s, 1H), 8.96 (d, 1H, J=2.2 Hz), 8.89 (m, 1H), 8.67 (s, 1H), 8.41 (m, 1H), 8.29(s, 1H), 8.25 (d, 1H, J=0.7 Hz), 8.07 (dd, 1H), 7.94 (d, 1H, J=2.2 Hz), 7.41 (d, 1H, J=0.6 Hz), 6.17 (s, 2H). MS=451.36 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.

1. temperatureHeat
2. temperatureCool the mixture
3. customseparate the organic layer
4. extractionExtract the aqueous layer with EtOAc (3×5 mL)
5. customdry
6. filtrationFilter the dried
7. extractionextract
8. concentrationconcentrate under vacuum
9. customto afford crude product
10. customPurify the crude product by HPLC