8-Hydroxyquinoline → 4-(Benzyloxy)-1-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yl)pyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 5-bromo-1-(2,2-dimethoxyethyl)-1H-indazole (4.0, 14 mmol), 4-(benzyloxy)pyridin-2(1H)-one (3.1 g, 16 mmol), K2CO3 (2.1 g, 16 mmol), 8-hydroxyquinoline (310 mg, 2.1 mmol) and CuI (3.1 g, 16 mmol) in DMSO (20 mL) was evacuated for 30 minutes under high vacuum then backfilled with nitrogen. The mixture was stirred under nitrogen at 130° C. for 20 h and then allowed to cool. The mixture was diluted with 20% MeOH/NH4OH (10:1) in CH2Cl2 (200 mL), stirred for 15 min, and then loaded onto a silica plug. The material was eluted through the plug with 20% MeOH/NH4OH (10:1) in CH2Cl2 (400 ml) and then concentrated. The residue was dissolved in CH2Cl2, washed with LiCl (4×100 mL) and brine (1×100 mL), dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (120 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 80% methylene chloride over 60 min at 40 mL/min) gave the title compound (4.96 g, 85%) as a light orange solid 1H NMR (300 MHz, CDCl3) δ 8.04 (s, 1H), 7.66 (d, J=1.6 Hz, 1H), 7.56 (d, J===8.9 Hz, 1H), 7.45-7.33 (m, 6H), 7.27 (d, J===2.9 Hz, 1H), 6.12-6.04 (m, 2H), 5.05 (s, 2H), 4.76 (t, J=5.3 Hz, 1H), 4.59 (d, J=5.3 Hz, 2H), 3.37 (s, 6H).

Provenance & Evidence