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

HRID 2411242Notes

Reaction equation

HRID 2411242 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 (2.88 g), 1-(3,5-dimethylpyridin-2-yl)piperazine (2.32 g) described in Preparation Example 79 and 1-hydroxybenzotriazole 1 hydrate (1.64 g) were dissolved 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 obtained 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 obtained residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-f6576658e1fe49e2812e86ef1e29586f
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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