Hydrochloric Acid → 5-(4-chloro-2-(1-cyclopropylethylcarbamoyl)phenylcarbamoyl)-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl 4-methylbenzenesulfonate

HRID 1641443Notes

Reaction equation

HRID 1641443 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=[C:13]([OH:23])[CH2:12]2)=[O:10])=[C:4]([C:24](=[O:31])[NH:25][CH:26]([CH:28]2[CH2:30][CH2:29]2)[CH3:27])[CH:3]=1.[H-].[Na+].[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1.Cl>CN(C)C=O>[CH3:44][C:34]1[CH:39]=[CH:38][C:37]([S:40]([O:23][C:13]2[CH2:12][CH:11]([C:9](=[O:10])[NH:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[C:24](=[O:31])[NH:25][CH:26]([CH:28]3[CH2:29][CH2:30]3)[CH3:27])[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=2)(=[O:42])=[O:41])=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 178464833HCID 178464833, compound

Product 1

HCID 866399065-(4-chloro-2-(1-cyclopropylethylcarbamoyl)phenylcarbamoyl)-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl 4-methylbenzenesulfonateYield 91.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixed liquid comprising 2.0 g of N-(4-chloro-2-(1-cyclopropylethylcarbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-3-hydroxy-4,5-dihydro-1H-pyrazole-5-carboxamide and 41 ml of N,N-dimethylformamide was cooled to 0° C., and 0.2 g of sodium hydride (60% oil suspension) was added. After stirring for one hour, 1.2 g of p-toluenesulfonyl chloride was added at 0° C. After stirring for 1.5 hours, the reaction liquid was poured to 120 ml of a 1 M HCl aqueous solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 1/1) to obtain 2.45 g of the desired product in the form of a paste.

Workup

  1. stirringAfter stirring for 1.5 hours
  2. customthe reaction liquid
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 1/1)

Sources & evidence

ORD record
ord-8b3e0cb66c5644d1a6dc7218aa5469d7
Source dataset
uspto-grants-2012_02
Patent number
US08115006B2

Reaction notes

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