3,6-Dihydro-2H-pyran-4-boronic acid pinacol ester → 6-(3,6-dihydro-2H-pyran-4-yl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

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Reaction Conditions

Reaction Steps

A mixture of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 12, 1.0 g, 3.48 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.49 g, 6.96 mmol) and Pd(PPh3)2Cl2 (0.24 g, 0.35 mmol) in aqueous Na2CO3 solution (2 M, 5.2 ml) and 1,2-dimethoxyethane (40 ml) was heated for 1.5 h at 100° C. under an atmosphere of argon. The cooled reaction mixture was then partitioned between aqueous NaHCO3 solution and EtOAc, the organic layer washed with brine, dried over MgSO4 and evaporated. The residue was then purified by normal phase chromatography using a 40 g RediSep® column, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were then combined and evaporated to give the title compound as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 6.96 (s, 1H), 6.52 (s, br, 1H), 5.54 (s, br, 1H), 5.11 (s, 1H), 4.17-4.14 (m, 2H), 3.77 (t, 2H), 3.28-3.21 (m, 2H), 3.25 (s, 6H), 2.65 (t, 2H), 2.26-2.20 (m, 2H), 1.80-1.72 (m, 2H). (UPLC-MS 3) tR 0.55 min; ESI-MS 291.2 [M+H]+.

Provenance & Evidence