Dimethylformamide → 1-(4-Chloro-2-cyclopropylphenyl)-N-(2-(2-fluorophenyl)-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide

HRID 1478806Notes

Reaction equation

HRID 1478806 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C=O)C.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]([CH3:24])=[C:22]([C:25]([OH:27])=O)[N:21]=[N:20]2)=[C:15]([CH:28]2[CH2:30][CH2:29]2)[CH:14]=1.[NH2:31][C:32]1[C:33](=[O:46])[N:34]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])[N:35]([CH3:38])[C:36]=1[CH3:37].C(N(CC)CC)C>C(Cl)Cl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]([CH3:24])=[C:22]([C:25]([NH:31][C:32]3[C:33](=[O:46])[N:34]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[F:45])[N:35]([CH3:38])[C:36]=3[CH3:37])=[O:27])[N:21]=[N:20]2)=[C:15]([CH:28]2[CH2:30][CH2:29]2)[CH:14]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 431636614-Amino-2-(2-fluorophenyl)-1,5-dimethyl-1H-pyrazol-3(2H)-one2×HCID 1185132721-(4-Chloro-2-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Product 1

HCID 1185132701-(4-Chloro-2-cyclopropylphenyl)-N-(2-(2-fluorophenyl)-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of oxalyl chloride (0.035 ml, 0.396 mmol) and DMF (0.056 ml, 0.720 mmol) in DCM (10 ml) was added 1-(4-chloro-2-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid (100 mg, 0.360 mmol) and the mixture was stirred for 30 mins. Further oxalyl chloride (0.035 ml, 0.396 mmol) was added to the reaction mixture and it was stirred for 1 hr. 4-Amino-2-(2-fluorophenyl)-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate B) (88 mg, 0.396 mmol) was added followed by triethylamine (0.151 ml, 1.080 mmol) and the mixture was stirred at RT for 1 hr. The resulting mixture was diluted with DCM, washed with 0.1 M HCl(aq) and sat. NaHCO3(aq). The organic extracts were passed through a phase separating cartridge and concentrated under reduced pressure to give an oil. The oil was absorbed onto silica and purified by chromatography eluting with 0-10% MeOH in TBME. The product fractions were combined and concentrated under reduced pressure to give a yellow glassy solid which was recrystallised from EtOH. The solid was collected by filtration and dried on the vacuum line to give the title compound as a white solid.

Workup

  1. stirringwas stirred for 1 hr
  2. stirringthe mixture was stirred at RT for 1 hr
  3. washwashed with 0.1 M HCl(aq) and sat. NaHCO3(aq)
  4. customseparating cartridge
  5. concentrationconcentrated under reduced pressure
  6. customto give an oil
  7. customThe oil was absorbed onto silica
  8. custompurified by chromatography
  9. washeluting with 0-10% MeOH in TBME
  10. concentrationconcentrated under reduced pressure
  11. customto give a yellow glassy solid which
  12. customwas recrystallised from EtOH
  13. filtrationThe solid was collected by filtration
  14. customdried on the vacuum line

Sources & evidence

ORD record
ord-e29fa6c200574697a9055c3e7b9574c1
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

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