Dimethylformamide → 1-(2-Chloro-4-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 1478801Notes

Reaction equation

HRID 1478801 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15]([CH3:16])=[C:14]([C:17]([OH:19])=O)[N:13]=[N:12]1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[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.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10]2)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15]([CH3:16])=[C:14]([C:17]([NH:31][C:32]2[C:33](=[O:46])[N:34]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[F:45])[N:35]([CH3:38])[C:36]=2[CH3:37])=[O:19])[N:13]=[N:12]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 431636614-Amino-2-(2-fluorophenyl)-1,5-dimethyl-1H-pyrazol-3(2H)-one2×HCID 1185132751-(2-chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Product 1

HCID 1185132691-(2-Chloro-4-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 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(2-chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid (Example 10, step 3) (95 mg, 0.342 mmol), oxalyl chloride (0.045 ml, 0.513 mmol) and DMF (0.053 ml, 0.684 mmol) in DCM (5 ml) was stirred at RT for 15 mins. 4-Amino-2-(2-fluorophenyl)-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate B) (83 mg, 0.376 mmol) was added to the mixture followed by triethylamine (0.143 ml, 1.026 mmol) and this was stirred at RT for 30 mins. 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 a brown 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. The solid was dissolved in 1:1 EtOAc:Et2O, washed with water (2×), brine, dried over MgSO4, filtered and concentrated under reduced pressure to give the title compound as a yellow glassy solid.

Workup

  1. washwashed with 0.1 M HCl(aq) and sat. NaHCO3(aq)
  2. customseparating cartridge
  3. concentrationconcentrated under reduced pressure
  4. customto give a brown oil
  5. customThe oil was absorbed onto silica
  6. custompurified by chromatography
  7. washeluting with 0-10% MeOH in TBME
  8. concentrationconcentrated under reduced pressure
  9. customto give a yellow glassy solid
  10. washEt2O, washed with water (2×), brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4616cbca8ea54b1f97bc84b8bed66af4
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

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