反应详情

The coupling reaction of 3-chloro-2-methylbenzenesulphonyl chloride (2 eq.) with 2-methylbenzimidazole (1 eq.) under the condition described above yielded a mixture of 3-chloro-N-[1-(3-chloro-2-methylbenzenesulphonyl)-2-methyl-1H-benzoimidazol-5-yl]-2-methyl-benzenesulphonamide and 3-chloro-N-[1-(3-chloro-2-methylbenzenesulphonyl)-2-methyl-1H-benzoimidazol-6-yl]-2-methyl-benzenesulphonamide in 1:1 ratio as judged by 1HNMR. 1H NMR (270 MHz, DMSO): δ 10.7 (2H, s, 2×NH), 7.86-7.96 (3H, m, ArH), 7.65-7.78 (5H, m, ArH), 7.52-7.58 (5H, m, ArH), 7.25-7.40 (3H, m, ArH), 7.07 (2H, t, J=8.2 Hz, ArH), 2.61 (3H, s, CH3), 2.58 (3H, s, CH3), 2.54 (6H, s, 2×CH3), 2.39 (3H, s, CH3), 2.33 (3H, s, CH3). The mixture (200 mg) was dissolved in THF (15 mL), N-hydroxybenzotriazole (200 mg) was added. After stirred at rt for 48 h, the mixture was partitioned between ethyl acetate and 5% sodium bicarbonate. The organic phase was washed with brine, dried over sodium sulphate and concentrate in vacuo to give a yellow residue, which was purified with flash chromatography (methanol/DCM gradient elution). Off white amorphous powder was obtained. TLC single spot at Rf 10.38 (10% methanol/DCM); HPLC purity 99% (tR 2.0 min in 10% water-methanol); 1H NMR (270 MHz, DMSO): δ 12.1 (1H, s, NH), 10.3 (1H, s, NH), 7.78 (1H, d, J=7.9 Hz, ArH), 7.68 (1H, d, J=7.9 Hz, ArH), 7.29-7.35 (2H, m, ArH), 7.12 (1H, s, ArH), 6.83 (1H, dd, J=8.4, 1.8 Hz, ArH), 2.63 (3H, s, CH3), 2.41 (3H, s, CH3); APCI-MS 334 (M−H+); FAB-HRMS calcd for C15H15ClN3O2S (MH+) 336.0573, found 336.0583.

1. customabove yielded
2. customthe mixture was partitioned between ethyl acetate and 5% sodium bicarbonate
3. washThe organic phase was washed with brine
4. dry with materialdried over sodium sulphate
5. concentrationconcentrate in vacuo
6. customto give a yellow residue, which
7. customwas purified with flash chromatography (methanol/DCM gradient elution)
8. customOff white amorphous powder was obtained