Water → N-(4-Chlorobenzyl)-2-(((3R)-3-hydroxypyrrolidin-1-yl)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

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Reaction Conditions

Reaction Steps

N,N-Diisopropylethylamine (0.48 mL) and N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 2, 0.500 g) were added to a solution of (R)-3-hydroxypyrrolidine (0.22 mL) in DMF (30 mL). The reaction mixture was heated to 90° C. for 2 h. The mixture was allowed to cool to room temperature, poured into water (60 mL), and extracted with ethyl acetate (4×50 mL) then CH2Cl2 (2×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The resulting solid was purified by column chromatography (CH2Cl2/methanol; 98/2, 97/3, 95/5) followed by recrystallization from ethyl acetate to yield 0.360 g of the title compound as a pale yellow solid. Physical characteristics. M.p. 189-190° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.64, 8.54, 7.41-7.32, 6.85, 4.73, 4.55, 4.22-4.16, 3.93, 3.68, 2.78-2.74, 2.68-2.62, 2.52-2.47, 2.41-2.37, 2.02-1:94, 1.58-1.50; MS (ESI+) m/z 416 (M+H)+; [α]25D=−3 (CH2Cl2).

Provenance & Evidence