Cesium carbonate → [2-Isobutoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine

Participants

Reaction Steps

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.

Provenance & Evidence