反应详情

To a stirring solution of chlorosulfonyl isocyanate (0.35 g, 5 mmol) in CH2Cl2 (20 mL) at 0° C. was added pyrrolidine (0.18 g, 5 mmol) at such a rate that the reaction temperature did not rise above 5° C. After stirring for 2 h, a solution of Example 41 (1.10 g, 6.5 mmol) and triethylmine (0.46 g, 9 mmol) in CH2Cl2 (20 mL) was added. When the addition was complete, the mixture was allowed to warm to RT and stirred overnight. The reaction mixture was poured into 10% HCl (10 mL) saturated with NaCl , the organic layer was separated and the aqueous layer extracted with ether (20 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo, purified by preparative HPLC to yield (pyrrolidine-1-carbonyl)sulfamic acid 3-[3-tert-butyl-5-(3-naphthalen-1-yl-ureido)-pyrazol-1-yl]phenyl ester (40 mg). 1H NMR (CDCl3): δ 9.12 (brs, 1H), 8.61 (brs, 1H), 7.85–7.80 (m, 3H), 7.65 (d, J=8.0 Hz, 2H), 7.53–7.51 (m, 1H), 7.45–7.25 (m, 5H), 6.89 (s, 4H), 3.36–3.34 (brs, 1H), 3.14–3.13 (brs, 2H), 1.69 (brs, 2H), 1.62 (brs, 2H), 1.39 (s, 9H); MS (ESI) m/z: 577 (M+H+).

1. customdid not rise above 5° C
2. additionWhen the addition
3. stirringstirred overnight
4. customthe organic layer was separated
5. extractionthe aqueous layer extracted with ether (20 mL)
6. dry with materialThe combined organic layers were dried (Na2SO4)
7. concentrationconcentrated in vacuo
8. custompurified by preparative HPLC