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

HRID 1804013Notes

Reaction equation

HRID 1804013 reaction equation
[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[Br:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][C:17]=1[F:25].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[Br:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([N:12]2[CH2:11][CH2:10][N:9]([C:3]3[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=3)[CH2:14][CH2:13]2)=[O:21])=[CH:18][C:17]=1[F:25]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27733414-Bromo-3-fluorobenzoic acidHCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazine

Product 1

HCID 58484572(4-Bromo-3-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(3,5-Dimethylpyridin-2-yl)piperazine (2.87 g) described in Preparation Example 47 was dissolved in N,N-dimethylformamide (38 ml), 4-bromo-3-fluorobenzoic acid (3.29 g), 1-hydroxybenzotriazole 1 hydrate (2.43 g) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (3.45 g) were added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was poured into water under cooling, and extracted with ethyl acetate. The organic layer was washed twice with water, washed with saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane). Then, ethyl acetate and hexane were added and the mixture was stirred at room temperature. The solid was collected by filtration and dried under reduced pressure to give the title compound (3.97 g).

Workup

  1. temperatureunder cooling
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed twice with water
  4. washwashed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by column chromatography (ethyl acetate:hexane)
  8. additionThen, ethyl acetate and hexane were added
  9. stirringthe mixture was stirred at room temperature
  10. filtrationThe solid was collected by filtration
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-568f000455b64c37b998cac25f091c65
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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