Dimethylformamide → HCID 67024496, compound

HRID 389123Notes

Reaction equation

HRID 389123 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[N:15]([CH3:16])[C:14]([C:17]([CH3:29])([O:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])[CH3:18])=[N:13][N:12]=1)[C:5]([OH:7])=O.C1C=CC2N(O)N=[N:36][C:34]=2C=1.CN(C=O)C.CN.C1COCC1>O>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[N:15]([CH3:16])[C:14]([C:17]([CH3:18])([O:19][C:20]2[C:21]([F:28])=[CH:22][C:23]([F:27])=[CH:24][C:25]=2[F:26])[CH3:29])=[N:13][N:12]=1)[C:5]([NH:36][CH3:34])=[O:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 58244041HCID 58244041, compoundHCID 66615946Methylamine tetrahydrofuran

Product 1

HCID 67024496HCID 67024496, compoundYield 110.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-chloro-4-{4-methyl-5-[1-methyl-1-(2,4,6-trifluorophenoxy)ethyl]-4H-1,2,4-triazol-3-yl}benzoic acid (204 mg), WSC•monohydrochloride (138 mg), HOBt (98 mg) and DMF (4 ml) were mixed and stirred for 30 minutes. A 2M methylamine-THF solution (0.72 ml) was added thereto, followed by stirring for 30 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, a 1M aqueous sodium hydroxide solution and then saturated brine in this order, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1 to 30:1). The residue was dissolved in ethyl acetate, 4M hydrogen chloride-ethyl acetate (1 ml) was added thereto, and the solvent was evaporated under reduced pressure. The resulting solid was washed with hexane to obtain 3-chloro-N-methyl-4-{4-methyl-5-[1-methyl-1-(2,4,6-trifluorophenoxy)ethyl]-4H-1,2,4-triazol-3-yl}benzamide monohydrochloride (126 mg), as a white solid.

Workup

  1. stirringby stirring for 30 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materiala 1M aqueous sodium hydroxide solution and then saturated brine in this order, and dried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1 to 30:1)
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. addition4M hydrogen chloride-ethyl acetate (1 ml) was added
  9. customthe solvent was evaporated under reduced pressure
  10. washThe resulting solid was washed with hexane

Sources & evidence

ORD record
ord-1a40ddba02f3427888ea43505a4e567f
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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