Hydrochloric Acid → 1-(4-chlorophenyl)-N-methyl-5-phenyl-N''-(piperidin-1-ylsulfonyl)-4,5-dihydro-1H-pyrazole-3-carboximidamide

HRID 19762Notes

Reaction equation

HRID 19762 reaction equation
[N:1]1([S:7]([NH:10][C:11]([C:13]2[CH2:17][CH:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:15]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:14]=2)=O)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)(Cl)Cl.Cl.C[CH2:39][N:40](C(C)C)C(C)C>ClC1C=CC=CC=1>[N:1]1([S:7]([NH:10][C:11]([C:13]2[CH2:17][CH:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:15]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:14]=2)=[N:40][CH3:39])(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24819Phosphorus pentachlorideHCID 81531DiisopropylethylamineHCID 68692403N-[(piperidin-1-yl)sulfonyl]-1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxamide

Product 1

HCID 117122961-(4-chlorophenyl)-N-methyl-5-phenyl-N''-(piperidin-1-ylsulfonyl)-4,5-dihydro-1H-pyrazole-3-carboximidamideYield 49%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
140 °C

Procedure

Part B: A stirred mixture of N-[(piperidin-1-yl)sulfonyl]-1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxamide (2.23 gram, 5 mmol), PCl5 (1.15 g, 5.5 mmol) and chlorobenzene (50 ml) is heated for 90 minutes at 140° C. After cooling the mixture to room temperature, followed by concentration in vacuo, the residue is dissolved in dichloromethane and methylamine.HCl (0.34 g, 5 mmol) and DIPEA (1.74 ml, 10 mmol) are successively added. The resulting mixture is stirred for 1 hour at room temperature, twice washed with water, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue is further purified by flash chromatography (silica gel, dichloromethane), followed by crystallization from diisopropyl ether to give N-[(piperidin-1-yl)sulfonyl]-N′-methyl-1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxamidine (1.12 gram, 49% yield). Melting point: 141-144° C. Rf (silica gel, diethyl ether=0.2).

Workup

  1. temperatureAfter cooling the mixture to room temperature
  2. concentrationfollowed by concentration in vacuo
  3. dissolutionthe residue is dissolved in dichloromethane
  4. stirringThe resulting mixture is stirred for 1 hour at room temperature
  5. washtwice washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue is further purified by flash chromatography (silica gel, dichloromethane)
  10. customfollowed by crystallization from diisopropyl ether

Sources & evidence

ORD record
ord-485028f1bd454ea9b7e27e459b6630d6
Source dataset
uspto-grants-2010_06
Patent number
US07745476B2

Reaction notes

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