Hydrochloric Acid → Hydrochloric Acid

Participants

Reaction Steps

4N HCl in dioxane (2 mL, 8.00 mmol) was added to a stirred solution of a TFA salt of (1R,3S,5R)-tert-butyl 3-(5-(6-(4-(2-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.10 g, 0.12 mmol) in CH2Cl2 (20 mL) and the resulting yellow suspension was stirred at rt for 2 h. The reaction was concentrated under vacuum and the resulting residue was triturated with Et2O to yield an HCl salt of methyl (S)-1-((1R,3S,5R)-3-(5-(4-(6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate HCl (47 mg) as a yellow solid. LC-MS [M+H]+=656; Rt=1.73 min is product. Column Luna 3u C18 2×50 mm; start % B: 0, final % B: 100 Solvent A: 10% Acetonitrile/90% H2O+1% TFA; Solvent B: 90% Acetonitrile/10% H2O+1% TFA; flow rate 4 ml/min. Run time: 5 min. Purity=95%. 1H NMR (500 MHz, DMSO-d6) δ ppm 14.47-15.18 (2H, m), 9.77-10.61 (2H, m), 8.30-8.42 (2H, m), 8.17 (1H, s), 7.93-8.10 (10H, m), 7.27 (1H, d, J=8.55 Hz), 5.08 (1H, t, J=7.93 Hz), 4.71 (1H, t, J=8.39 Hz), 4.40-4.46 (1H, m), 3.77 (1H, br. s.), 3.52-3.58 (3H, m), 3.38-3.44 (1H, m), 2.52-2.61 (3H, m), 2.39 (1H, dt, J=13.58, 6.64 Hz), 2.14-2.21 (1H, m), 1.94 (2H, dd, J=8.24, 4.88 Hz), 1.15 (1H, d, J=5.80 Hz), 0.93 (4H, d, J=6.71 Hz), 0.75-0.89 (6H, m).

Provenance & Evidence