Piperazine → HCID 58707256, compound

HRID 1910595Notes

Reaction equation

HRID 1910595 reaction equation
S1C=C(N)C2C=CC=CC1=2.FC1C=C(F)C=CC=1S(C)(=O)=O.C(N(CC)C(C)C)(C)C.F[C:33]1[CH:34]=[CH:35][C:36]([S:49]([CH3:52])(=[O:51])=[O:50])=[C:37]([NH:39][C:40]2[C:41]3[CH:48]=[CH:47][CH:46]=[CH:45][C:42]=3[S:43][CH:44]=2)[CH:38]=1.[NH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1>CN(C)C=O.C(#N)C.O>[CH3:52][S:49]([C:36]1[CH:35]=[CH:34][C:33]([N:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)=[CH:38][C:37]=1[NH:39][C:40]1[C:41]2[CH:48]=[CH:47][CH:46]=[CH:45][C:42]=2[S:43][CH:44]=1)(=[O:51])=[O:50]

Participants

9

Reactant 5

HCID 4837PiperazineHCID 81531Diisopropylethylamine2×HCID 27583362,4-Difluoro-1-(methylsulfonyl)benzeneHCID 111944231-Benzothiophen-3-amineHCID 67147307HCID 67147307, compound

Product 1

HCID 58707256HCID 58707256, compoundYield 16%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of benzo[b]thiophen-3-amine (1.1 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (1.1 mmol) and N,N-diisopropylethylamine (4.00 mmol) in N,N-dimethylformamide (2 mL) was stirred at 110° C. for 16 h. The reaction was cooled to room temperature, poured over water and extracted with diethyl ether. The solvent was concentrated in vacuo and the residue was used without further purification for the following reaction. N-(5-fluoro-2-(methylsulfonyl)phenyl)benzo[b]thiophen-3-amine (0.3 mmol), piperazine (8.0 mmol), N,N-diisopropylethylamine (4.00 mmol) were stirred at 80° C. in dry acetonitrile (3 mL) for 16 h. The solvent was evaporated and the residue was dissolved in dichloromethane and washed with water. The dichloromethane was evaporated and the crude compound was purified by silica chromatography using 10% methanol in dichloromethane to afford the title compound (16% yield). 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.88 (m, 1H), 7.71 (d, 1H), 7.71 (m, 1H), 7.66 (m, 1H), 7.14 (s, 1H), 6.46 (d, 1H), 6.41 (dd. 1H), 3.13 (s, 3H), 3.11 (m, 4H), 2.91 (m, 4H); MS (ESI) m/z: 388.2 (M++1).

Workup

  1. extractionextracted with diethyl ether
  2. concentrationThe solvent was concentrated in vacuo
  3. customthe residue was used without further purification for the following reaction
  4. customThe solvent was evaporated
  5. dissolutionthe residue was dissolved in dichloromethane
  6. washwashed with water
  7. customThe dichloromethane was evaporated
  8. customthe crude compound was purified by silica chromatography

Sources & evidence

ORD record
ord-f67c26dcaa0a4c4bbaac865b66b5bca0
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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