Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 241 mg) in acetonitrile (8 mL) with 7-bromo-4-methyl-2H-benzo[b][1,4]thiazin-3(4H)-one (Example 28, step (i), 120 mg) was treated with aqueous sodium carbonate solution (2M, 0.465 mL) and then nitrogen was bubbled through the mixture. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85° C. under nitrogen for 18 h. A further addition of sodium carbonate solution (2M, 0.2 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was made and the mixture was heated at 85° C. for a further 18 h. A further addition of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 20 mg) was made and the mixture was heated at 85° C. for 18 h. The mixture was purified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0) to afford the sub-titled compound (132 mg).

Provenance & Evidence