1-Hydroxybenzotriazole → (4-Bromo-2,6-difluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

HRID 1804006Notes

Reaction equation

HRID 1804006 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:5]([C:6]([OH:8])=O)=[C:4]([F:12])[CH:3]=1.[CH3:13][C:14]1[C:15]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[N:16][CH:17]=[C:18]([CH3:20])[CH:19]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]([F:12])[C:5]([C:6]([N:24]2[CH2:25][CH2:26][N:21]([C:15]3[C:14]([CH3:13])=[CH:19][C:18]([CH3:20])=[CH:17][N:16]=3)[CH2:22][CH2:23]2)=[O:8])=[C:9]([F:11])[CH:10]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27732984-Bromo-2,6-difluorobenzoic acidHCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazine

Product 1

HCID 58484761(4-Bromo-2,6-difluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

4-Bromo-2,6-difluorobenzoic acid (2.875 g) and 1-(3,5-dimethylpyridin-2-yl)piperazine (2.32 g) described in Preparation Example 47 and 1-hydroxybenzotriazole 1hydrate (1.64 g) were dissolve in N,N-dimethylformamide (50 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (2.32 g) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol) to give the title compound (4.33 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customthe solvent was evaporated
  4. customThe residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-95d5f25be16044f08fa9f57c992621b7
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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