Methyl iodide → 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]-N-(cyclohexylmethyl)-N-methylazetidine-1-carboxamide

HRID 1402739Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1402739
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([CH:14]3[CH2:17][N:16]([C:18]([NH:20][CH2:21][CH:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[O:19])[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:30]I>CN(C=O)C>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([CH:14]3[CH2:15][N:16]([C:18]([N:20]([CH2:21][CH:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)[CH3:30])=[O:19])[CH2:17]3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 468522983-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]-N-(cyclohexylmethyl)azetidine-1-carboxamide

Produkt 1

HCID 468524463-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]-N-(cyclohexylmethyl)-N-methylazetidine-1-carboxamideAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]-N-(cyclohexylmethyl)azetidine-1-carboxamide (26 mg, 0.069 mmol) in dry DMF (1 ml) at 0° C. under a nitrogen atmosphere was added sodium hydride (4.1 mg of a 60% dispersion in mineral oil, 0.103 mmol). The resulting suspension was stirred at 0° C. for 30 min. Methyl iodide (4.3 μl, 0.069 mmol) was added and the reaction mixture allowed to warm to RT and was stirred for 16 hrs. The reaction mixture was poured onto ice-water, extracted with EtOAc (3×5 ml), the combined organics washed with brine (5 ml), dried (MgSO4), filtered and concentrated at reduced pressure. Purification by preparative HPLC provided the title compound (5.6 mg, 21% yield) as colourless oil.

Aufarbeitung

  1. temperatureto warm to RT
  2. stirringwas stirred for 16 hrs
  3. additionThe reaction mixture was poured onto ice-water
  4. extractionextracted with EtOAc (3×5 ml)
  5. washthe combined organics washed with brine (5 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customPurification by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9d7ed35375094bbbb01dd0ecb7bd6c74
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08912176B2

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