Potassium Carbonate → 1,1-dimethylethyl 4-({4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)-3-oxo-1-piperazinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 1,1-dimethylethyl 4-[(4-bromophenyl)methyl]-3-oxo-1-piperazinecarboxylate (for a preparation, see Intermediate 72) (111 mg, 0.3 mmol), 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 52) (250 mg, 0.600 mmol), potassium carbonate (124 mg, 0.900 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (21.95 mg, 0.030 mmol) then filled with 1,4-dioxane (3 mL) and water (1 mL) and flushed with nitrogen. The resulting mixture was stirred under microwave irradiation at 120° C. for 30 min then cooled to room temperature. Most of the 1,4-dioxane was removed in vacuo and the residue was partitioned between AcOEt and water. The layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge (gradient: 5 to 25% (10% MeOH in DCM) in DCM) gave 1,1-dimethylethyl 4-({4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)-3-oxo-1-piperazinecarboxylate (180 mg, 0.311 mmol, 104% yield) which was used in the next step without further purification.

Provenance & Evidence