反应详情

Heat a mixture of 4-chloro-2-isobutoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine (79.2 mg, 0.2 mmol), 2-amino-5-trifluoromethylpyridine hydrochloride (39.6 mg, 0.2 mmol), xantphos (11.6 mg, 0.1 mmol), Pd2(dba)3 (18.3 mg, 0.1 mmol) and Cs2CO3 (130 mg, 0.4 mmol) in dioxane (2.0 mL) at 100° C. for 20 hours. Cool the mixture, concentrate under vacuum, dilute with water (5.0 mL), extract with EtOAc (3×3 mL) and dry with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by flash column chromatography to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) d 0.88 (6H, d, J=1.7), 1.89 (1H, m), 3.37 (2H, d, J=1.6), 4.67 (2H, s), 7.79 (1H, m), 7.96(1H, d, J=2.1), 8.19 (1H, d, J=1.7), 8.42 (1H, d, J=2.0), 8.82(2H, m), 8.98(1H, d, J=1.1), 9.34 (1H, d, J=2.1). MS=523.2 (M+H). IC50 in standard assay of capsaicin receptor activity is less than 10 nanomolar.

1. temperatureHeat
2. temperatureCool the mixture
3. concentrationconcentrate under vacuum
4. additiondilute with water (5.0 mL)
5. extractionextract with EtOAc (3×3 mL)
6. dry with materialdry with MgSO4
7. filtrationFilter the dried
8. extractionextract
9. concentrationconcentrate under vacuum
10. customto afford crude product
11. customPurify by flash column chromatography