1,4-Dioxane → N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-iodo-1H-pyrazole-5-carboxamide

HRID 1843059Notes

Reaction equation

HRID 1843059 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9](=[O:14])[NH:10][CH:11]1[CH2:13][CH2:12]1.[I:15][C:16]1[C:17]([C:25]([F:31])([F:30])[C:26]([F:29])([F:28])[F:27])(C(O)=O)[NH:18][N:19]([CH3:21])[CH:20]=1.Cl.C(N=C=NCCCN(C)C)C.[O:44]1CCOC[CH2:45]1>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:45]([C:20]2[N:19]([CH3:21])[N:18]=[C:17]([C:25]([F:30])([F:31])[C:26]([F:27])([F:28])[F:29])[C:16]=2[I:15])=[O:44])=[CH:4][C:3]=1[C:9](=[O:14])[NH:10][CH:11]1[CH2:13][CH2:12]1

Participants

5

Reactant 4

HCID 312751,4-Dioxane2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167752405-amino-2-chloro-N-cyclopropylbenzamideHCID 866600834-iodo-1-methyl-3-pentafluoroethyl-1H-pyrazolecarboxylic acid

Product 1

HCID 46219667N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-iodo-1H-pyrazole-5-carboxamide

Procedure

0.49 g (2.34 mmol) of 4-chloro-3-(cyclopropylcarbamoyl)aniline dissolved in 0.5 ml of dioxane are added dropwise to a solution of 1.28 g (2.34 mmol) of 4-iodo-1-methyl-3-pentafluoroethyl-1H-pyrazolecarboxylic acid and 0.54 g (2.81 mmol) of 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride in 20 ml of dioxane and the reaction mixture is stirred for three days at room temperature. The majority of the dioxane is distilled off at reduced pressure on a rotary evaporator and the residue is admixed with 20 ml of water. The aqueous phase is extracted three times with ethyl acetate and the organic phase is then washed three times with saturated sodium chloride solution. After drying over sodium sulphate, the solvent is distilled off at reduced pressure on a rotary evaporator and the residue is purified by means of flash chromatography on silica gel (eluent: cyclohexane/ethyl acetate). This gives 0.70 g of N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-1-methyl-3-(pentafluoroethyl)-4-iodo-1H-pyrazole-5-carboxamide (53%) as an oil.

Workup

  1. distillationThe majority of the dioxane is distilled off at reduced pressure on a rotary evaporator
  2. extractionThe aqueous phase is extracted three times with ethyl acetate
  3. washthe organic phase is then washed three times with saturated sodium chloride solution
  4. dry with materialAfter drying over sodium sulphate
  5. distillationthe solvent is distilled off at reduced pressure on a rotary evaporator
  6. customthe residue is purified by means of flash chromatography on silica gel (eluent: cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-8e1cd3f73fae409891f031f295b06659
Source dataset
uspto-grants-2015_02
Patent number
US08946234B2

Reaction notes

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