Hydrochloric Acid → 1-methylethyl((cis)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

Participants

Reaction Conditions

Reaction Steps

1-Methylethyl[(cis)-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 12) (120 mg, 0.288 mmol), [2-(4-bromo-1H-pyrazol-1-yl)ethyl]dimethylamine (for a preparation see Intermediate 15) (85 mg, 0.390 mmol) and potassium carbonate (51.8 mg, 0.375 mmol) were stirred in ethanol (1.5 ml) and toluene (1.5 ml) and the mixture degassed. Tetrakis(triphenylphosphine)palladium(0) (16.65 mg, 0.014 mmol) was added, the mixture degassed again and heated to reflux (85° C.) overnight. The mixture was cooled to room temperature, partitioned between ethyl acetate (35 ml) and sat. sodium hydrogen carbonate:water (1:1, 10 ml). The aqueous layer was run off and the organic washed (sat. sodium hydrogen carbonate:water (1:1, 10 ml)), dried (magnesium sulfate) and evaporated to an orange residue. The residue was loaded on to a 12+M Biotage silica column and eluted with DCM:2M Methanolic ammonia (0 to 15%). The product containing fractions were evaporated to dryness then dissolved in MeOH (1 ml) and 1.25M HCl in MeOH (0.128 ml, 0.159 mmol) was added and the mixture evaporated to an off white solid (59 mg). LCMS (Method C): Rt=0.64, MH+=428

Provenance & Evidence