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

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Reaction Steps

Heat a mixture of 4-chloro-2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine (115 mg, 0.3 mmol), 2-amino-5-trifluoromethylpyridine hydrochloride (60 mg, 0.3 mmol), xantphos (17.5 mg, 0.03 mmol), Pd2(dba)3 (27.3 mg, 0.03 mmol)and Cs2CO3 (195 mg, 0.6 mmol) in dioxane (3.0 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 3.64 (3H, s), 4.63 (2H, s), 7.41 (1H, d, J=2.1), 7.52 (1H, m), 7.81 (1H, d, J=2.1), 7.92(1H, d J=2.0), 8.15 (1H, d, J=2.0), 8.68 (1H, s), 8.88(1H, d, J=1.2), 9.02 (1H, d, J=2.2). MS =481.2 (M+H). IC50 in standard assay of capsaicin receptor activity is less than 10 nanomolar.

Provenance & Evidence