1,2-Dichloroethane → (S)-Methyl 2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of (S)-methyl 2-((S)-2-amino-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (966 mg, 2.02 mmol) and (S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid (Advanced ChemTech, 411 mg, 2.02 mmol) in DMF (20 mL) was added EDC (465 mg, 2.43 mmol), followed by HOAt (330 mg, 2.43 mmol). NMM (667 μl, 6.07 mmol) was then added, and the resulting reaction mixture was stirred at 0° C. for 30 min, then warmed to room temperature and stirred for 4 h. The reaction mixture was then poured into a separatory funnel containing EtOAc and sat. aq. NaHCO3 solution. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with 1N HCl (2×) and 10% LiCl, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (1.34 g, 2.02 mmol, 100%) as a light yellow foam, which was used without further purification. MS (ESI+) m/z 663.3 (M+H)+.

Provenance & Evidence