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

HRID 1910597Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1910597
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

Komponenten

9

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-673c1c0b24b2413ba3b7b4fd4ba16154
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604021B2

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