Diisopropylethylamine → N,N-Dibutyl-4-chloro-1-(2-(3-(dimethylamino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide

Participants

Reaction Steps

To a solution of 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 91F, 36 mg, 0.058 mmol) in DCE (1.0 mL) was added 1-chloro-N,N-2-trimethylprop-1-en-1-amine (15 μL, 0.12 mmol). The resulting reaction mixture was stirred at room temperature for 1.5 h. A solution of N,N-dimethyl-2,5-dihydro-1H-benzo[e][1,3]diazepin-3-amine (Rodriguez, H. R. et al., J. Org. Chem., 33:670-676 (1968)) (11 mg, 0.058 mmol) in THF (1.0 mL) was then added, followed by DMAP (7 mg, 0.058 mmol) and i-Pr2EtN (50 μL, 0.29 mmol). The resulting reaction mixture was stirred at room temperature for 12 h, then concentrated in vacuo and purified by preparative HPLC to give the title compound (11 mg, 24%). 1H NMR (DMSO-d6, mixture of amide rotamers) δ 10.31 (br s, 1H), 8.56 (br s, 1H), 8.32-7.87 (m, 7H), 7.77-7.57 (m, 2.5H), 7.33-7.05 (m, 3H), 6.98 (br s, 0.5H), 5.09-4.53 (m, 3H), 4.08 (br s, 2H), 3.86-2.85 (m, 9H), 2.14 (s, 3H), 1.71-1.41 (m, 3H), 1.36-1.07 (m, 3H), 0.99-0.80 (m, 4.5H), 0.54 (br s, 3.5H); MS(ESI+) m/z 796.8 (M+H)+.

Provenance & Evidence