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

HRID 2426044Notes

Reaction equation

HRID 2426044 reaction equation
COC1C=C2C(=CC=1)C(N)CCC2.FC1C=C(F)C=CC=1S(C)(=O)=O.C(N(C(C)C)CC)(C)C.F[C:36]1[CH:37]=[CH:38][C:39]([S:55]([CH3:58])(=[O:57])=[O:56])=[C:40]([NH:42][CH:43]2[C:52]3[C:47](=[CH:48][C:49]([O:53][CH3:54])=[CH:50][CH:51]=3)[CH2:46][CH2:45][CH2:44]2)[CH:41]=1.[NH:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1>CN(C)C=O.C(#N)C.O>[CH3:54][O:53][C:49]1[CH:48]=[C:47]2[C:52](=[CH:51][CH:50]=1)[CH:43]([NH:42][C:40]1[CH:41]=[C:36]([N:59]3[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]3)[CH:37]=[CH:38][C:39]=1[S:55]([CH3:58])(=[O:57])=[O:56])[CH2:44][CH2:45][CH2:46]2

Participants

9

Reactant 5

HCID 4837PiperazineHCID 382506-Methoxy-1,2,3,4-tetrahydro-1-naphthalenylamineHCID 81531Diisopropylethylamine2×HCID 27583362,4-Difluoro-1-(methylsulfonyl)benzeneHCID 67147323N-(5-Fluoro-2-(methylsulfonyl)phenyl)-1,2,3,4-tetrahydro-6-methoxynaphthalen-1-amine

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-(methylsulfonyl)phenyl)-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-bff0376735724fcb9fcb86c832ca677f
Source dataset
uspto-grants-2011_06
Patent number
US07968538B2

Reaction notes

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