Hydrochloric Acid → 1-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (45 mg, 0.049 mmol) and PPh3 (38 mg, 0.15 mmol) in THF (4.0 mL) and water (0.4 mL) was added 1N aq. NaOH solution (0.2 mL, 0.20 mmol). The resulting reaction mixture was heated at 50° C. for 3 h and then acidified (pH=1) with 1N aq. HCl solution. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to give the title compound (33 mg, 72%) as a white solid. 1H NMR (CD3OD, mixture of amide rotamers) δ 9.16 (s, 1H), 8.29-7.88 (m, 4H), 7.83-7.58 (m, 3H), 7.40-7.08 (m, 4H), 6.99 (br s, 1H), 5.04 (br s, 0.5H), 4.76-4.41 (m, 4H), 4.27-2.66 (m, 18.5H), 2.42-2.20 (m, 3H), 1.64-0.72 (m, 13H), 0.60 (br s, 1H); MS(ESI+) m/z 898.1 (M+H)+.

Provenance & Evidence