Piperazine → 1,2,3,4-Tetrahydro-6-methoxy-N-(2-(methylsulfonyl)-5-(piperazin-1-yl)phenyl)naphthalen-1-amine

HRID 1910602Notes

Reaction equation

HRID 1910602 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([NH2:13])[CH2:8][CH2:7][CH2:6]2.F[C:15]1[CH:20]=[C:19](F)[CH:18]=[CH:17][C:16]=1[S:22]([CH3:25])(=[O:24])=[O:23].C(N(C(C)C)CC)(C)C.[NH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>CN(C)C=O.C(#N)C.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([NH:13][C:15]1[CH:20]=[C:19]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[CH:18]=[CH:17][C:16]=1[S:22]([CH3:25])(=[O:24])=[O:23])[CH2:8][CH2:7][CH2:6]2

Participants

8

Reactant 4

HCID 4837PiperazineHCID 382506-Methoxy-1,2,3,4-tetrahydro-1-naphthalenylamineHCID 81531Diisopropylethylamine2×HCID 27583362,4-Difluoro-1-(methylsulfonyl)benzene

Product 1

HCID 587073331,2,3,4-Tetrahydro-6-methoxy-N-(2-(methylsulfonyl)-5-(piperazin-1-yl)phenyl)naphthalen-1-amineYield 21%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1,2,3,4-tetrahydro-6-methoxynaphthalen-1-amine (1.0 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (1.0 mmol) and diisopropylethylamine (4.0 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-(methylsulfonyephenyl)-1,2,3,4-tetrahydro-6-methoxynaphthalen-1-amine (0.5 mmol), piperazine (8.0 mmol), N,N-diisopropylethylamine (4.0 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 (21% yield). 1H NMR (400 MHz, CDCl3): δ 7.61 (d, 1H), 7.21 (d, 1H), 6.72 (dd, 1H), 6.64 (d, 1H), 6.28 (dd, 1H), 6.23 (d, 1H), 4.62 (m, 1H), 3.79 (s, 3H), 3.28 (t, 4H), 3.00 (t, 4H), 2.93 (s, 3H), 2.81 (m, 2H), 1.94 (m, 4H); MS (ESI) m/z: 415.55 (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-4d54f9c039204dbdab7f82150e758377
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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