Cesium carbonate → HCID 131734955, compound

Participants

Reaction Conditions

Reaction Steps

A 5 ml microwave vial was loaded with 2-chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 10) (110 mg, 0.321 mmol), rac-3-((1r,2r)-2-((dimethylamino)methyl)cyclopropyl)-1H-indole-6-carbonitrile (50 mg, 0.209 mmol), Pd(OAc)2 (5 mg, 0.022 mmol), Brettphos (CAS 1070663-78-3) (35 mg, 0.065 mmol) and Cs2CO3 (powder, 80 mesh, 210 mg, 0.645 mmol). The vial was sealed, evacuated and flushed with nitrogen 4×. Dioxane (3 ml) was added and the vial evacuated and backfilled with nitrogen 4 times. The reaction was heated to 110° C. for 12 hours. LCMS shows m/e+=546, consistent with [M+H]+ of product. Only trace of indole starting material remaining. The reaction mixture was allowed to cool to room temperature, diluted with acetonitrile and filtered through Celite. The Celite was washed with acetonitrile. The combined solutions were evaporated to dryness. The crude was purified by column chromatography on silica. (40 g cartridge, load sample as solution in dichloromethane, elute with gradient from 100% DCM to 100% EtOAc (product doesn't elute), then a gradient from 100% dichloromethane to 80% DCM+20% (MeOH+1% aq, conc. NH4OH). Product containing fractions were combined and evaporated to dryness to give 92.8 mg pale yellow film (+/−)-2-(6-cyano-3-((1r,2r)-2-((dimethylamino)methyl)cyclopropyl)-1H-indol-1-yl)-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (92.8 mg, 0.163 mmol)

Provenance & Evidence