Triisopropyl phosphite → [4-(3,8-Dihydroimidazo[4,5-d]dipyrido[2,3-b:4',3'-f]azepin-2-yl)cyclohexyl]acetonitrile

関与物質

反応手順

A solution of [4-(3-hydroxy-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b:4′,3′-f]azepin-2-yl)cyclohexyl]acetonitrile (7.0 g, 0.019 mol) and triisopropyl phosphite (20 mL, 0.08 mol) in N,N-dimethylacetamide (20 mL) was heated at 160° C. for 2 hours and was then concentrated in vacuo. The residue was purified by column chromatography on silica gel (5% trimethylamine 7.5% methanol and 87.5% ethyl acetate) yielding 4.10 g of product as a 9:1 mixture of the two diastereomers. The pure cis and trans isomers could be obtained by preparative HPLC. 1H NMR (300, DMSO-d6): δ 12.73 and 12.01 (br s, 1H), 7.83-7.99 (m, 4H), 7.70 and 7.46 (m, 1H), 6.77 (m, 1H), 2.54-2.63 (m, 1H), 2.49 (m, 2H), 1.84-2.02 (m, 4H), 1.50-1.79 (m, 3H), 1.09-1.24 (m,2H).

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