2-Methoxypyridine-4-carbaldehyde → HCID 59276493, compound

Participants

Reaction Conditions

Reaction Steps

2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methanol. The reaction was performed in two batches of starting material (0.397 g and 0.310 g) according to the following procedure and recombined for work-up and purification. A suspension of 5-bromo-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-c]pyridin-2-amine (0.397 g, 1.111 mmol) in dry tetrahydrofuran (6.0 mL) was cooled to −78° C. The mixture was then reacted with n-butyl lithium (0.933 mL, 2.333 mmol, 2.5 M in hexanes). The reaction was stirred at low temperature for 1 h. A solution of 2-methoxyisonicotinaldehyde (0.32 g, 2.333 mmol) in dry tetrahydrofuran (3 mL) was then added dropwise. Low temperature was maintained for 2 h. Checked after 30 min, the reaction had progressed to a mixture of desired product contaminated with de-halogenated starting material. The reaction was quenched with water and the crude was extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and evaporated to dryness. The residue was purified by biotage column chromatography using the following gradient: 800 mL gradient 10-50% ethyl acetate in hexanes, then 1.100 L at 50% ethyl acetate in hexanes. Desired fractions were combined and evaporated to dryness. (2-Methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methanol (0.574 g, 1.382 mmol, 69.8% yield) was collected as a yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ (ppm) 8.04 (d, J=5.47 Hz, 1H), 7.63-7.70 (m, 3H), 7.54 (d, J=8.59 Hz, 2H), 7.47 (d, J=9.37 Hz, 1H), 7.32 (d, J=7.03 Hz, 1H), 7.04 (s, 1H), 7.01 (d, J=5.47 Hz, 1H), 6.32 (s, 1H), 3.86 (s, 3H); MS (ESI): m/z 416.2 [M+1]+.

Provenance & Evidence