Water → HCID 67024346, compound

HRID 389148Notes

Reaction equation

HRID 389148 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]([CH3:30])([C:14]2[N:18]([CH3:19])[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])=[N:16][N:15]=2)[CH3:13])=[C:6]([CH:10]=1)[C:7](O)=[O:8].C1C=N[C:34]2[N:37](O)N=N[C:33]=2[CH:32]=1.C1(N)CC1.O>CN(C=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]([CH3:30])([C:14]2[N:18]([CH3:19])[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:27])([F:28])[F:29])=[N:16][N:15]=2)[CH3:13])=[C:6]([CH:10]=1)[C:7]([NH:37][CH:34]1[CH2:33][CH2:32]1)=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 69828CyclopropylamineHCID 181649HOAtHCID 58244031HCID 58244031, compound

Product 1

HCID 67024346HCID 67024346, compoundYield 124%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzoic acid (300 mg) was dissolved in DMF (9 ml), and WSC•monohydrochloride (200 mg), HOAt (140 mg) and cyclopropylamine (0.235 ml) were added thereto, followed by stiffing at room temperature for 2 hours. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and then saturated brine in this order, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting oily product was purified by silica gel column chromatography (chloroform:methanol=100:1). The resulting oily product was dissolved in ethyl acetate and 4M hydrogen chloride-ethyl acetate (1 ml) was added thereto, followed by concentrating under reduced pressure. The resulting solid was washed with ethyl acetate to obtain, as a white solid, 5-chloro-N-cyclopropyl-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzamide monohydrochloride (218 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialsaturated brine in this order, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting oily product was purified by silica gel column chromatography (chloroform:methanol=100:1)
  6. dissolutionThe resulting oily product was dissolved in ethyl acetate
  7. addition4M hydrogen chloride-ethyl acetate (1 ml) was added
  8. concentrationby concentrating under reduced pressure
  9. washThe resulting solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-d7492c1fc478473389e01371948d8dfd
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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