Piperazine → PRX-07034 free base

HRID 1910576Notes

Reaction equation

HRID 1910576 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:22][CH3:23])=[C:6]([CH:8]([NH:10][C:11]2[CH:16]=[C:15](F)[CH:14]=[CH:13][C:12]=2[S:18]([CH3:21])(=[O:20])=[O:19])[CH3:9])[CH:7]=1.[NH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:22][CH3:23])=[C:6]([CH:8]([NH:10][C:11]2[CH:16]=[C:15]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[CH:14]=[CH:13][C:12]=2[S:18]([CH3:21])(=[O:20])=[O:19])[CH3:9])[CH:7]=1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 81531DiisopropylethylamineHCID 44240863N-(1-(5-Chloro-2,3-dimethoxyphenyl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine

Product 1

HCID 11532574PRX-07034 free baseYield 3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of [1-(5-chloro-2,3-dimethoxy-phenyl)-ethyl]-(5-fluoro-2-methanesulfonyl-phenyl)-amine (0.52 g, 1.34 mmol), piperazine (0.23 g, 2.68 mmol) and N,N-diisopropylethylamine (0.47 mL, 2.68 mmol) in acetonitrile was stirred at 80° C. for 24 h. The reaction mixture was cooled down and concentrated under reduced pressure. The residue was taken up in dichloromethane, washed with water, dried and concentrated in vacuo to yield the crude residue which was purified by preparative TLC (0.5% NH4OH/9.5% methanol/dichloromethane) to afford [1-(5-chloro-2,3-dimethoxy-phenyl)-ethyl]-(2-methanesulfonyl-5-piperazin-1-yl-phenyl)-amine (17 mg, 3%). 1H NMR (400 MHz, CD3OD): δ 7.42 (d, 1H), 6.87 (m, 2H), 6.25 (dd, 1H), 5.90 (s, 1H), 4.87 (m, 1H), 3.85 (s, 1H), 3.81 (s, 1H), 3.05-3.2 (m, 4 H), 3.78 (m, 4H), 1.49 (d, 3H). MS (ESI) m/z: Calculated: 453.98; Observed: 454.4 (M+H+); 476.4 (M+Na+); 930.8 (2M+Na+). Mol. Wt.: 453.98 (C21H28ClN3O4S).

Workup

  1. temperatureThe reaction mixture was cooled down
  2. concentrationconcentrated under reduced pressure
  3. washwashed with water
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customto yield the crude residue which
  7. customwas purified by preparative TLC (0.5% NH4OH/9.5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-65ab863937e74a558571b9a81c7b8273
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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