Hydrochloric Acid → (Pyrrolidine-1-carbonyl)sulfamic acid 3-[3-tert-butyl-5-(3-naphthalen-1-yl-ureido)-pyrazol-1-yl]phenyl ester

HRID 16950

Reaction equation

HRID 16950 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[NH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.[C:13]([C:17]1[CH:21]=[C:20]([NH:22][C:23]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)=[O:24])[N:19]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([OH:42])[CH:37]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].Cl.[Na+].[Cl-]>C(Cl)Cl>[C:13]([C:17]1[CH:21]=[C:20]([NH:22][C:23]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)=[O:24])[N:19]([C:36]2[CH:37]=[C:38]([O:42][S:2](=[O:4])(=[O:3])[NH:5][C:6]([N:8]3[CH2:12][CH2:11][CH2:10][CH2:9]3)=[O:7])[CH:39]=[CH:40][CH:41]=2)[N:18]=1)([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 31268PyrrolidineHCID 70918Chlorosulfonyl isocyanateHCID 218673141-[3-Tert-butyl-1-(3-hydroxyphenyl)-1h-pyrazol-5-yl]-3-(naphthalene-1-yl)urea

Product 1

HCID 25226698(Pyrrolidine-1-carbonyl)sulfamic acid 3-[3-tert-butyl-5-(3-naphthalen-1-yl-ureido)-pyrazol-1-yl]phenyl esterYield 1.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-4004865e153a4770b4e3660e1db5d903
Source dataset
uspto-grants-2010_06
Patent number
US07737283B2

Linked notes

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