Sulfur, trifluoro(N-methylmethanaminato)- → 9-(1-fluoro-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

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Reaction Conditions

Reaction Steps

(Dimethylamino)sulfur trifluoride (0.010 mL, 0.18 mmol) was added to a stirred solution of 9-(1-hydroxy-2-morpholinoethyl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 83, 49 mg, 0.090 mmol) in ACN (1 mL). After 4 h, additional (dimethylamino)sulfur trifluoride (0.035 mL, 0.36 mmol) was added and the mixture was stirred at 60° C. for 20 h, and cooled to room temperature. The reaction mixture was diluted with aqueous sodium bicarbonate (3 mL) and extracted with DCM (2×3 mL). The combined organic layers were concentrated under a stream of nitrogen and the residue was taken up in methanol, and filtered. Purification (HPLC, 10-75% ACN in water) afforded the title compound but retained impurities. The product was diluted with aqueous sodium bicarbonate (3 mL) and extracted with DCM (2×3 mL). The combined organic layers were concentrated under a stream of nitrogen. Purification (FCC, SiO2, 0 to 40%, IPA/EtOAc) afforded the title compound (9 mg, 21%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 2.58-2.72 (m, 4H), 2.82 (ddd, J=27.98, 13.93, 3.39 Hz, 1H), 3.01 (ddd, J=18.85, 14.15, 7.53 Hz, 1H), 3.72-3.76 (m, 4H), 3.76 (s, 3H), 5.75 (s, 2H), 5.84 (d, J=47.93 Hz, 1H), 6.76-6.88 (m, 2H), 7.60 (d, J=8.66 Hz, 2H), 8.36 (s, 1H), 8.64 (d, J=1.88 Hz, 1H), 8.80 (s, 1H). [M+H]=439.1.

Provenance & Evidence