Sodium Bicarbonate → 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [(cis)-2-(4-fluoro-phenyl)-cyclopropyl]-amide

HRID 1479152Notes

Reaction equation

HRID 1479152 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:11][C@H:10]2[NH2:12])=[CH:5][CH:4]=1.C([O-])(O)=O.[Na+].[F:18][CH:19]([F:29])[C:20]1[C:24]([C:25](Cl)=[O:26])=[CH:23][N:22]([CH3:28])[N:21]=1.CCOC(C)=O.CCCCCC>ClCCl>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[CH2:11][C@H:10]2[NH:12][C:25]([C:24]2[C:20]([CH:19]([F:29])[F:18])=[N:21][N:22]([CH3:28])[CH:23]=2)=[O:26])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 21226206Ethyl acetate hexaneHCID 89760855cis-2-(4-Fluoro-phenyl)-cyclopropylamine hydrochloride

Product 1

HCID 897693453-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [(cis)-2-(4-fluoro-phenyl)-cyclopropyl]-amideYield 85.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

cis-2-(4-Fluoro-phenyl)-cyclopropylamine hydrochloride (0.153 g, 0.815 mmol) was dissolved in dichloromethane (4.5 ml) and stirred with NaHCO3 (1 M, 4.5 ml). 3-(difluoromethyl)-1-methyl-1H-pyrazol-4-carbonyl chloride (0.190 g, 0.978 mmol) was added dropwise. After three hours rapid stirring tlc (50% EtOAc/hexane) showed the reaction to be finished. The mixture was separated between dichloromethane and water, washed with NaCl (sat), dried (MgSO4), and evaporated to yield 245 mg of nearly pure product, which was washed with cyclohexane to yield 215 mg (85%) of the product as a white solid m.p. 141-143° C.

Workup

  1. customthe reaction
  2. customThe mixture was separated between dichloromethane and water
  3. washwashed with NaCl (sat)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto yield 245 mg of nearly pure product, which
  7. washwas washed with cyclohexane

Sources & evidence

ORD record
ord-cc0f5096f63e4d2180640a0713242056
Source dataset
uspto-grants-2016_08
Patent number
US09408392B2

Reaction notes

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