1,2-Dichloroethane → HCID 178522414, compound

HRID 1012142Notes

Reaction equation

HRID 1012142 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:3]=1[CH2:4][NH:5][C:6]1[C:7]([C:11](O)=O)=[N:8][NH:9][CH:10]=1.[Br:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([NH2:30])[C:21]=1[NH2:31].C(Cl)CCl.C1C=CC2N([OH:45])N=NC=2C=1>CN(C=O)C>[Br:19][C:20]1[C:21]2[N:31]=[C:11]([C:7]3[C:6]([NH:5][C:4](=[O:45])[C:3]4[C:2]([F:1])=[CH:17][CH:16]=[CH:15][C:14]=4[F:18])=[CH:10][NH:9][N:8]=3)[NH:30][C:22]=2[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 7357853-Bromo-4,5-diaminobenzotrifluorideHCID 178524951HCID 178524951, compound

Product 1

HCID 178522414HCID 178522414, compoundYield 5.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(2,6-difluorobenzylamino)-1H-pyrazole-3-carboxylic acid (520 mg, 1.96 mmol) (Example 16D), 3-bromo-5-trifluoromethyl-1,2-benzenediamine (500 mg, 1.96 mmol), EDC (413 mg, 2.15 mmol) and HOBt (290 mg, 2.15 mmol) in DMF (20 ml) was stirred at ambient temperature for 16 h and then reduced in vacuo. The residue was partitioned between EtOAc and brine and the organic portion dried (MgSO4), filtered and evaporated. The amide intermediate was chromatographed using EtOAc-P.E. (1:4-1:0). The intermediate amide (271 mg), (LC/MS: Rt 3.31, [M+H]+ 505), was dissolved in AcOH (3 ml) then heated at reflux for 1 h. The reaction mixture was allowed to cool at which time a solid crystallised out, that was filtered, washed with P.E. and dried to give the title compound (50 mg). (LC/MS: Rt 3.42, [M+H]+ 486,488)

Workup

  1. customThe residue was partitioned between EtOAc and brine
  2. dry with materialthe organic portion dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe amide intermediate was chromatographed
  6. dissolutionThe intermediate amide (271 mg), (LC/MS: Rt 3.31, [M+H]+ 505), was dissolved in AcOH (3 ml)
  7. temperaturethen heated
  8. temperatureat reflux for 1 h
  9. temperatureto cool at which time a solid
  10. customcrystallised out,
  11. filtrationthat was filtered
  12. washwashed with P.E
  13. customand dried

Sources & evidence

ORD record
ord-7619eeb849ee4984bc3fcfc030159ed8
Source dataset
uspto-grants-2011_07
Patent number
US07977477B2

Reaction notes

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