Methyl iodide → {1-[4-(8-Methyl-4-oxo-2-phenyl-4,8-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037301Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1037301
[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19](=[O:37])[C:20]4[C:21]([O:29][C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:22]3[C:26](=[CH:27][CH:28]=4)[NH:25][N:24]=[CH:23]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:41]I>CN(C=O)C>[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19](=[O:37])[C:20]4[CH:28]=[CH:27][C:26]5[C:22](=[CH:23][N:24]([CH3:41])[N:25]=5)[C:21]=4[O:29][C:30]=3[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67067723{1-[4-(4-Oxo-2-phenyl-4,7-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Produkt 1

HCID 67067704{1-[4-(8-Methyl-4-oxo-2-phenyl-4,8-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterAusbeute 32,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of {1-[4-(4-oxo-2-phenyl-4,7-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (65 mg, 0.13 mmol) in DMF (3 mL) at 0° C. under an atmosphere of N2 was added sodium hydride (60% in mineral oil, 6 mg, 0.15 mmol). After 5 min, methyl iodide (10 μL, 0.16 mmol) was added. After a further 2 hours, the reaction was quenched with H2O, partitioned between EtOAc and H2O and the phases were separated. The organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 70% ethyl acetate in cyclohexane) to afford the title compound as a white solid (22 mg, 32%). LCMS (Method B): RT=4.26 min, [M+H]+=522. Also obtained was {1-[4-(7-methyl-4-oxo-2-phenyl-4,7-dihydro-pyrano[2,3-e]indazol-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester as an oil (41 mg, 60%). LCMS (Method B): RT=4.42 min, [M+H]+=522.

Aufarbeitung

  1. waitAfter a further 2 hours
  2. customthe reaction was quenched with H2O
  3. custompartitioned between EtOAc and H2O
  4. customthe phases were separated
  5. washThe organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6933d4b6f375446aada4d3d5c6f1fc75
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08546376B2

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