Triethylamine → 3-((4-(4-Amino-2-chloro-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide

HRID 1878365Notes

Reaction equation

HRID 1878365 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([Cl:11])[C:3]=1[F:12].[C:13]([NH:17][C:18](=[O:32])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:20]=1)([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl.C(OCC)(=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:29]2[CH2:28][CH2:27][N:26]([CH2:25][C:21]3[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=3)[C:18]([NH:17][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:32])[CH2:31][CH2:30]2)=[O:8])=[C:4]([Cl:11])[C:3]=1[F:12]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 66877987N-tert-butyl-3-(piperazin-1-ylmethyl)benzamideHCID 668788144-Amino-2-chloro-3-fluorobenzoic acid

Product 1

HCID 579176283-((4-(4-Amino-2-chloro-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamideYield 28.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-amino-2-chloro-3-fluorobenzoic acid (2.64 mmol, 500 mg) and N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide (2.54 mmol, 700 mg) and triethylamine (10.76 mmol, 1.5 mL, 1089 mg) in dichloromethane (30 mL) was added 1-propanephosphonic acid cyclic anhydride (6.75 mmol, 4 mL, 4296 mg, 50% solution in ethyl acetate). After 2 hours stirring, ethyl acetate was added. The organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride. The organic mixture was dried sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane) to yield the title compound (325 mg). MS (ESI) m/z 447.1 [M+H]+

Workup

  1. washThe organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bffba28e8e7944c4bfd7c73aaaa0d0a4
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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