Triethylamine → 3-((4-(4-amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide

HRID 1878330Notes

Reaction equation

HRID 1878330 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].[C:12]([NH:16][C:17](=[O:31])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:19]=1)([CH3:15])([CH3:14])[CH3:13].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(#N)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:28]2[CH2:27][CH2:26][N:25]([CH2:24][C:20]3[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=3)[C:17]([NH:16][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:31])[CH2:30][CH2:29]2)=[O:8])=[CH:4][C:3]=1[F:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 99714-Amino-3-fluorobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66877987N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide

Product 1

HCID 668785283-((4-(4-amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamideYield 26.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Amino-3-fluorobenzoic acid (500 mg, 3.22 mmol), N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide (888 mg, 3.22 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (926 mg, 4.83 mmol, EDCl) and triethylamine (984 mg, 898 μl, 6.44 mmol) were combined and stirred in acetonitrile (10 mL) at room temperature overnight (under nitrogen). The reaction was concentrated under reduced pressure. The residue was taken up in dichloromethane (30 mL) and washed with water. The organic phase was dried over sodium sulfate and concentrated under vacuum. The residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 4% methanol/dichloromethane) to give the title compound (355 mg).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. washwashed with water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by silica chromatography (
  6. washeluting with a solvent gradient from dichloromethane to 4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-368dd9e57d79411d8fe928b3fd154b5d
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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