Piperazine → 1,2,3,4-tetrahydro-6,7-dimethoxy-N-(2-(methylsulfonyl)-5-(piperazin-1-yl)phenyl)naphthalen-1-amine

HRID 2426039Notes

Reaction equation

HRID 2426039 reaction equation
COC1C=C2C(=CC=1OC)C(N)CCC2.FC1C=C(F)C=CC=1S(C)(=O)=O.C(N(C(C)C)CC)(C)C.F[C:38]1[CH:39]=[CH:40][C:41]([S:59]([CH3:62])(=[O:61])=[O:60])=[C:42]([NH:44][CH:45]2[C:54]3[C:49](=[CH:50][C:51]([O:57][CH3:58])=[C:52]([O:55][CH3:56])[CH:53]=3)[CH2:48][CH2:47][CH2:46]2)[CH:43]=1.[NH:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1>CN(C)C=O.C(#N)C.O>[CH3:58][O:57][C:51]1[CH:50]=[C:49]2[C:54](=[CH:53][C:52]=1[O:55][CH3:56])[CH:45]([NH:44][C:42]1[CH:43]=[C:38]([N:63]3[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]3)[CH:39]=[CH:40][C:41]=1[S:59]([CH3:62])(=[O:61])=[O:60])[CH2:46][CH2:47][CH2:48]2

Participants

9

Reactant 5

HCID 4837PiperazineHCID 81531Diisopropylethylamine2×HCID 4290936,7-Dimethoxy-1,2,3,4-tetrahydronaphthalen-1-amine hydrochlorideHCID 27583362,4-Difluoro-1-(methylsulfonyl)benzeneHCID 67147543N-(5-Fluoro-2-(methylsulfonyl)phenyl)-1,2,3,4-tetrahydro-6,7-dimethoxynaphthalen-1-amine

Product 1

HCID 587073311,2,3,4-tetrahydro-6,7-dimethoxy-N-(2-(methylsulfonyl)-5-(piperazin-1-yl)phenyl)naphthalen-1-amineYield 17%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1,2,3,4-tetrahydro-6,7-dimethoxynaphthalen-1-amine (200.0 mg, 0.96 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (185.0 mg, 0.96 mmol) and diisopropylethylamine (496.0 mg, 3.84 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-6,7-dimethoxynaphthalen-1-amine (150 mg, 0.40 mmol), piperazine (683 mg, 7.90 mmol), N,N-diisopropylethylamine (510 mg, 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 (30 mg, 17% yield). 1H NMR (400 MHz, CDCl3): δ 7.63 (d, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 6.31 (m, 2H), 6.25 (d, 1H), 4.62 (m, 1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.30 (m, 4H), 3.02 (m, 4H), 2.94 (s, 3H), 2.72 (m, 2H), 1.84 (m, 4H); MS (ESI) m/z: 446.3 (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-b59f5ecb85a74f37a8a75a2d4b01d3a8
Source dataset
uspto-grants-2011_06
Patent number
US07968538B2

Reaction notes

Loading…