Boron Trichloride → HCID 86718903, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-1-(2-(3-((2-(benzyloxy)ethoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (Example 117, 35 mg, 0.039 mmol) in CH2Cl2 (1.0 mL) was cooled to −78° C., and boron trichloride (270 μL, 0.27 mmol) was added dropwise via syringe. The resulting solution was stirred at −78° C. for 1 h and then at room temperature overnight. Additional boron trichloride (270 μL, 0.27 mmol) was added, and the reaction mixture was stirred at room temperature for 5 h. After quenching with sat. aq. NH4Cl, the solution was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by preparative HPLC to give the title compound (10 mg, 31%). 1H NMR (1:1 CD3OD:CDCl3, mixture of amide rotamers) δ 8.65 (s, 1H), 8.40 (s, 0.5H), 8.19-8.11 (m, 1H), 8.09-7.83 (m, 4H), 7.63-7.52 (m, 2.5H), 7.47-7.30 (m, 1H), 7.26-6.98 (m, 3.5H), 6.88 (br s, 0.5H), 5.25 (d, J=18.3 Hz, 0.5H), 4.36-4.07 (m, 3H), 3.75-3.17 (m, 6.5H), 3.12-2.61 (m, 4H), 2.51 (d, J=16.4 Hz, 0.5H), 2.35-2.17 (m, 3.5H), 1.68-0.79 (m, 11.5H), 0.75-0.56 (m, 2.5H); MS(ESI+) m/z 814.2 (M+H)+.

Provenance & Evidence