3,4-Dichlorophenyl isocyanate → (3R)-N-(3,4-dichlorophenyl)-4-[(1-ethylpiperidin-3-yl)methyl]-3-methylpiperazine-1-carboxamide

HRID 2371145Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2371145
[CH3:1][C@H:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10]C(C)(C)C)=O)[CH2:3]1.CC1C=CC(S(O[CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][CH3:34])[CH2:28]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C.[Cl:50][C:51]1[CH:52]=[C:53]([N:58]=C=O)[CH:54]=[CH:55][C:56]=1[Cl:57]>C(#N)C.ClCCl>[Cl:50][C:51]1[CH:52]=[C:53]([NH:58][C:8]([N:4]2[CH2:5][CH2:6][N:7]([CH2:26][CH:27]3[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][CH3:34])[CH2:28]3)[C@H:2]([CH3:1])[CH2:3]2)=[O:10])[CH:54]=[CH:55][C:56]=1[Cl:57]

Komponenten

8

Edukt 5

HCID 76073,4-Dichlorophenyl isocyanateHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2756811(R)-1-Boc-3-methylpiperazineHCID 57656762(1-Ethylpiperidin-3-yl)methyl 4-methylbenzenesulfonate

Produkt 1

HCID 11531706(3R)-N-(3,4-dichlorophenyl)-4-[(1-ethylpiperidin-3-yl)methyl]-3-methylpiperazine-1-carboxamideAusbeute 67,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of tert-butyl (3R)-3-methylpiperazine-1-carboxylate (84 mg) and (1-ethylpiperidin-3-yl)methyl 4-methylbenzenesulfonate (150 mg) in acetonitrile (3 mL) was added potassium carbonate (233 mg). The mixture was heated to 100° C. in the microwave for 2 hours and then evaporated. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane. To a solution of the isolated material (50 mg) in methanol (5 mL) was added 4M HCl in dioxane (0.5 mL). The mixture was stirred overnight at room temperature and then evaporated to give a colourless oil. To a mixture of this oil in dichloromethane (10 mL) was added di-iso-propylethylamine (0.11 mL) and 3,4-dichlorophenylisocyanate (35 mg). The mixture was stirred for 15 minutes and then evaporated. The residue was purified using reverse phase HPLC eluting with a mixture of 5-95% acetonitrile in water to give the title compound as a white foam (52 mg, 30%).

Aufarbeitung

  1. customevaporated
  2. customThe residue was purified by silica column chromatography
  3. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane
  4. additionTo a solution of the isolated material (50 mg) in methanol (5 mL) was added 4M HCl in dioxane (0.5 mL)
  5. customevaporated
  6. customto give a colourless oil
  7. stirringThe mixture was stirred for 15 minutes
  8. customevaporated
  9. customThe residue was purified
  10. washeluting with a mixture of 5-95% acetonitrile in water

Quellen und Nachweise

ORD-Eintrag
ord-4ccaba3f6b124620ab1d0c550ad9db64
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08710224B2

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