Barium hydroxide → 3-(1,3-Dimethyl-10-(4-methylthiazol-2-yl)-2,4-dioxo-1,2,3,4,7,8-hexahydropyrimido[4,5-a]indolizin-5-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(1,3-dimethyl-2,4-dioxo-10-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4,7,8-hexahydropyrimido[4,5-a]indolizin-5-yl)benzonitrile (step 9) (202 mg, 0.44 mmol), 2-iodo-4-methylthiazole (Intermediate O) (90 mg, 0.40 mmol), dichloro[1,1′ bis(di-tert-butylphosphino)]ferrocene palladium (11) (13 mg, 0.02 mmol) and barium hydroxide (137 mg, 0.80 mmol) in acetonitrile/water (1:1, 2 mL) was stirred at room temperature for 45 minutes and at 80° C. for 1 hour. The reaction mixture was diluted with 1M HCl (10 mL) and was extracted with DCM (3×10 mL). The combined organic layers were filtered through a hydrophobic frit and the solvent removed under vacuum. Purified by chromatography on silica, eluting with 0.5% MeOH/DCM, 1% MeOH/DCM, 1.5-2.0% MeOH afforded the title product:

Provenance & Evidence