反应详情

Methanesulfonamide (96 mg, 1.00 mmol) was added to a solution of 3-{2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-benzoic acid (Example 2)(409 mg, 0.80 mmol), EDC (207 mg, 1.08 mmol) and DMAP (122 mg, 1.00 mmol) in DCM (20 ml) at room temperature. After stirring for 17 h, the mixture was washed with 5% KHSO4 (50 ml), brine (50 ml) and dried (MgSO4). Filtration and evaporation of the solvent gave the crude product which was purified by flash column chromatography (MeOH-DCM (1:10) to afford the title compound as a white crystalline solid (392 mg, 83%). 1H NMR (DMSO-d6) 9.99 (1H, s), 8.02 (1H, s), 7.63-7.36 (5H, m), 7.23 (1H, t), 7.13 (1H, d), 4.73 (2H, dd), 4.29 and 4.25 (2H, d×2), 3.24 (3H, s), 2.87 (1H, m), 1.80-1.48 (6H, m), 1.30-1.09 (13H, m). The compound was further characterised as the N-methyl-D-glucamine salt. Found: C, 53.93; H, 7.07; N, 10.17%; C30H37N5O6S.C7H17NO5.2.0H2O requires: C, 53.74; H, 7.07; N, 10.16%.

1. washthe mixture was washed with 5% KHSO4 (50 ml), brine (50 ml)
2. dry with materialdried (MgSO4)
3. filtrationFiltration and evaporation of the solvent
4. customgave the crude product which
5. customwas purified by flash column chromatography (MeOH-DCM (1:10)