Triethylamine → 1-(2,4-difluoro-phenyl)-5-[3-(4-methanesulfonyl-piperazin-1-yl)-pyridin-5-yl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole

HRID 2208014Notes

Reaction equation

HRID 2208014 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[CH:14]([C:15]2[CH:16]=[C:17]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:18]=[N:19][CH:20]=2)[CH2:13][C:12]([C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])=[N:11]1.C(N(CC)CC)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>ClCCl>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[CH:14]([C:15]2[CH:16]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([S:42]([CH3:41])(=[O:44])=[O:43])[CH2:23][CH2:22]3)[CH:18]=[N:19][CH:20]=2)[CH2:13][C:12]([C:27]([F:33])([F:32])[C:28]([F:29])([F:30])[F:31])=[N:11]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1184317551-(2,4-difluoro-phenyl)-5-[3-(piperazin-1-yl)-pyridin-5-yl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole hydrochloride

Product 1

HCID 1184320011-(2,4-difluoro-phenyl)-5-[3-(4-methanesulfonyl-piperazin-1-yl)-pyridin-5-yl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazoleYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(2,4-Difluoro-phenyl)-5-[3-(piperazin-1-yl)-pyridin-5-yl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole hydrochloride (30.0 mg, 0.06 mmol) prepared in Example 170, triethylamine (42.3 uL, 0.30 mmol) and methanesulfonyl chloride (10.4 mg, 0.09 mmol) were added to dichloromethane (1.0 mL). The reaction mixture was stirred at room temperature for 1 hour, washed with distilled water, 1N hydrochloride, a saturated solution of sodium hydrogen carbonate, and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=2/1) to give 15.0 mg of the titled compound as a yellow liquid.

Workup

  1. washwashed with distilled water, 1N hydrochloride
  2. dry with materiala saturated solution of sodium hydrogen carbonate, and brine, dried on anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give a yellow liquid residue
  5. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=2/1)

Sources & evidence

ORD record
ord-0b3a995ef27c426492184cf28a1c6973
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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