Hydrochloric Acid → HCID 52934333, compound

Participants

Reaction Steps

Sodium hydride (60% in mineral oil, 50 mg, 1.25 mmol) was added portionwise to a stirred solution of 1-methylethyl[(2S,4R)-1-acetyl-6-cyano-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 57) (350 mg, 1.1 mmol) in dry methanol (10 mL). The resulting mixture was stirred at room temperature for 48 h then was treated with aminoacetaldehyde dimethyl acetaldehyde (233 mg, 2.2 mmol) and acetic acid (1 mL, excess). The resulting mixture was refluxed for 2 h then was cooled to room temperature and treated with HCl (1M in water, 5 mL). The resulting mixture was refluxed for 1 h, cooled to room temperature and most of the methanol was removed in vacuo. The residue was diluted with water (10 mL) and basified by the addition of solid potassium carbonate (CARE: gas evolved). The resulting aqueous phase was extracted with AcOEt (3×10 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) followed by trituration of the adduct obtained with Et2O gave 1-methylethyl[(2S,4R)-1-acetyl-6-(1H-imidazol-2-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (14 mg, 0.039 mmol, 3.5%) as an off white solid.

Provenance & Evidence