Carbon Tetrachloride → 1-{1-[9-Methyl-8-(5-methyl-1,3,4-oxadiazol-2-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

Participants

Reaction Steps

N′-acetyl-9-methyl-6-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-9H-purine-8-carbohydrazide (85 mg, 0.19 mmol, 1 equiv) and triphenylphosphine (90 mg, 0.34 mmol, 1.8 equiv) were weighed out into a 2 dram vial and suspended in acetonitrile (1 mL). Diisopropylethylamine (165 mL, 0.95 mmol, 5 equiv) and carbontetrachloride (36 μL, 0.38 mmol, 2 equiv) were added and the reaction stirred at room temperature overnight during which time a precipitate formed. Analysis by LCMS indicated about a 40% conversion to the desired product. Neither heating to 80° C. for several hours, nor the addition of additional carbontetrachloride, DIPEA, or TPP furthered the cyclization. The precipitate was collected, dissolved in DMF (3.5 mL) and purified by preparative reverse-phase HPLC (acetonitrile/water with 1% formic acid). Fraction containing pure 1-{1-[9-methyl-8-(5-methyl-1,3,4-oxadiazol-2-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one were combined. The desired material precipitated upon concentration of the fractions, was collected by filtration, washed with water, and dried under vacuum, which resulted in the isolation of 16 mg of material. 1H NMR (400 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.33 (s, 1H), 7.16-7.10 (m, 1H), 6.93-6.82 (m, 3H), 4.53 (t, 1H), 4.03 (s, 3H), 2.59 (s, 3H), 2.30 (d, 2H), 1.83 (d, 2H). MS (EI) for C21H21N9O2: 432 (MH+).

Provenance & Evidence