反应详情

To a solution of 2-amino-4-difluoromethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (200 mg, 0.71 mmol) in DCM (15 mL), was added (CCl3O)2CO (151 mg, 0.7 equiv). The resulting mixture was stirred at r.t. for 1 h. The solvent was removed in vacuo and the residue was solubilized in THF. CH3SO2NHNH2 (86 mg, 1.1 equiv) was added and, after stirring at r.t. for 1 h, the mixture was treated with aq NaOH (1N, 0.78 mL) for 30 min. The solvent was removed in vacuo and water was added. The pH was adjusted to 3-4 by addition of 1N aq HCl. The aqueous phase was extracted with AcOEt (2×). The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. This solid was triturated in 15 mL of DCM/hexanes (1/1). The resulting solid was filtered off, washed with hexanes and dried to afford the title compound as an off-white solid (150 mg, 55%). ES-MS: m/z 386.3 [M+H]+, rt 4.16 min. 1H-NMR (DMSO-d6, 400 MHz) 12.04 (s, 1H), 10.34 (s, 1H); 7.93 (s, 1H); 7.55 (s, 1H); 7.52 (s, 1H); 6.83 (t, 1H, J=54 Hz), 6.34 (s, 1H). 3.62 (s, 3H); 3.17 (s, 1H)

1. customThe solvent was removed in vacuo
2. stirringafter stirring at r.t. for 1 h
3. customThe solvent was removed in vacuo and water
4. additionwas added
5. additionThe pH was adjusted to 3-4 by addition of 1N aq HCl
6. extractionThe aqueous phase was extracted with AcOEt (2×)
7. washwashed with brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated in vacuo
10. customto afford a crude solid
11. customThis solid was triturated in 15 mL of DCM/hexanes (1/1)
12. filtrationThe resulting solid was filtered off
13. washwashed with hexanes
14. customdried