Hydrochloric Acid → HCID 67540239, compound

Participants

Reaction Steps

The 4-piperazin-1-yl-quinazoline bis-hydrochloride (220 mg, 0.766 mmol), (S)-2-tert-butoxycarbonylamino-3-(4-chlorophenyl)-3-methyl-butyric acid (251 mg, 0.766 mmol, 1.0 equiv), 1-hydroxybenzotriazole (109 mg, 0.804 mmol, 1.05 equiv), and EDCI (154 mg, 0.804 mmol, 1.05 equiv) were dissolved/suspended in 6.0 mL of DMF. The mixture was treated with triethylamine (427 μL, 3.06 mmol) and allowed to stir overnight to completion. The reaction was partitioned between ethyl acetate and diluted NaHCO3 solution. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was eluted through a small plug of silica gel with ethyl acetate and concentrated in vacuo. The protected intermediate was immediately dissolved in 1 mL of dioxane and treated with 4M HCl in dioxane (1.92 mL, 7.66 mmol) at room temperature for four hours. The resulting precipitate was triturated with ether, then filtered to afford the (R)-2-amino-3-(4-chlorophenyl)-3-methyl-1-(4-quinazolin-4-yl-piperazin-1-yl)-butan-1-one bis-hydrochloride as a light-yellow solid (277 mg, 73%) upon drying under vacuum. 1H NMR (DMSO-d6, 400 MHz) δ 8.89 (s, 1H), 8.46 (brs, 3H), 8.17 (d, J=8.4 Hz, 1H), 8.06 (t, J=7.6 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 4.53 (brs, 1H), 4.09 (m, 3H), 3.90 (m, 3H), 3.32 (m, 1H), 3.04 (t, J=9.2 Hz, 1H), 1.51 (s, 3H), 1.43 (s, 3H). LCMS (APCI+) m/z 424 [M+H]+; Rt=1.90 min.

Provenance & Evidence