تفاعل #45228

معادلة التفاعل

chlorosulfonyl isocyanate

pyrrolidine

solution

1-[3-tert-butyl-1-(3-hydroxyphenyl)-1H-pyrazol-5-yl]-3-(naphthalene-1-yl)urea

HCl

NaCl

→

(pyrrolidine-1-carbonyl)sulfamic acid 3-[3-tert-butyl-5-(3-naphthalen-1-yl-ureido)-pyrazol-1-yl]phenyl ester

المردود 1.4%

المذيبات

CH2Cl2

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   أخرىdid not rise above 5° C
2. 2
   workup.ADDITIONWhen the addition
3. 3
   workup.STIRRINGstirred overnight
4. 4
   أخرىthe organic layer was separated
5. 5
   استخلاصthe aqueous layer extracted with ether (20 mL)
6. 6
   تجفيفThe combined organic layers were dried (Na2SO4)
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىpurified by preparative HPLC

الإجراء التجريبي

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+).

المصدر