Trifluoroacetic acid → HCID 71053028, compound

Participants

Reaction Conditions

Reaction Steps

N-(6-Chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (325 mg, 0.886 mmol), tetrakis(triphenylphosphine)palladium (0) (51.20 mg, 0.044 mmol), potassium carbonate (1.1 mL of 2 M, 2.21 mmol), and 1-(2-(methylsulfonyl)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (377 mg, 1.15 mmol) were combined in a scintillation vial containing 1,2-dimethoxyethane (8 mL). The reaction mixture was then stirred and heated to 80 degrees C. for 16 hours. The reaction was then allowed to cool to room temperature. The layers were then separated and the organic layer was evaporated to dryness, re-dissolved in 1 mL of N,N-dimethylformamide, and purified by reverse-phase preparative liquid chromatography utilizing a gradient of 0-99% acetonitrile (containing 0.035% trifluoroacetic acid (v/v)) in water (containing 0.05% trifluoroacetic acid (v/v)) to yield the product. The resulting trifluoroacetic acid salt was then dissolved in a minimum of dichloromethane (5 mL). This solution was then washed two times with a saturated aqueous solution of sodium bicarbonate, followed by two washes of a saturated aqueous solution of sodium chloride, followed by two washes of water. The organic layer was dried over sodium sulfate and then evaporated to dryness. The product was then further purified on 4 g of silica utilizing a gradient of 0-10% methanol in dichloromethane to yield the pure product (16.7 mg, 3.5%). ESI-MS m/z calc. 531.1. found 532.1 (M+1)+. Retention time 1.52 minutes. 1H NMR (400 MHz, CD3CN) δ 7.94 (d, J=8.4 Hz, 1H), 7.77 (s, 1H), 7.65 (d, J=2.3 Hz, 1H), 7.62-7.55 (m, 2H), 7.36-7.32 (m, 2H), 7.22 (d, J=8.2 Hz, 1H), 6.42 (d, J=9.4 Hz, 1H), 4.29 (t, J=6.7 Hz, 2H), 3.49 (t, J=6.7 Hz, 2H), 2.90 (s, 3H), 2.32 (s, 3H), 1.62-1.58 (m, 2H), 1.19-1.15 (m, 2H).

Provenance & Evidence