Potassium Hydroxide → 1-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

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Reaction Steps

1-Methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Example 4) (0.24 g, 0.650 mmol), potassium hydroxide (1.300 mL, 1.300 mmol), N,N-dimethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethanamine (for a preparation see Intermediate 115) (0.190 g, 0.715 mmol) and (1,3-bis(2,6-diisopropylphenyl)imidazolidene)(3-chloropyridyl)palladium(II) dichloride (0.03 g, 0.044 mmol) were dissolved in ethanol (10 mL) and 1,2-dimethoxyethane (DME) (10.00 mL) and the resulting mixture was degassed under house vacuum with several quenches with nitrogen then refluxed for three hours, cooled to room temperature, allowed to stand for 16 h then concentrated in vacuo. The residue was partitioned between water (30 mL) and EtOAc (30 mL) and the layer were separated. The organic phase was dried over MgSO4 and concentrated in vacuo. Purification of this residue by SP4 using a 25 G silica cartridge (gradient: 0 to 10% (2M NH3 in MeOH) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (137 mg, 0.320 mmol, 49.3% yield) as an amber oil.

Provenance & Evidence