Formic Acid → (1R,5R,6S)-6-[4-(4-Amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzo cyclohepten-6-yl)-phenyl]-tricyclo[3.2.1.0*2,4*]octane-3-carboxylic Acid Methyl Ester

HRID 2237636Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2237636
[NH2:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([C:13]3[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.[CH2:21]([O:23][C:24]([CH:26]([CH2:29][CH2:30][CH:31]=[CH:32][CH3:33])[CH2:27]C)=[O:25])C.N1CCCC[CH2:35]1.C(O)=O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C(Cl)(Cl)Cl.CO.CCOC(C)=O>[CH3:21][O:23][C:24]([CH:26]1[CH:27]2[CH:29]1[C@@H:30]1[CH2:31][C@H:32]2[C@@H:33]([C:16]2[CH:17]=[CH:18][C:13]([N:9]3[CH2:10][CH2:11][O:12][C:6]4[N:5]=[CH:4][N:3]=[C:2]([NH2:1])[C:7]=4[C:8]3=[O:20])=[CH:14][CH:15]=2)[CH2:35]1)=[O:25]

Komponenten

10

Edukt 4

HCID 284Formic AcidHCID 8082PiperidineHCID 593025304-Amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-oneHCID 131728124Oct-6-ene-3-carboxylic acid ethyl ester

Produkt 1

HCID 59302525(1R,5R,6S)-6-[4-(4-Amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzo cyclohepten-6-yl)-phenyl]-tricyclo[3.2.1.0*2,4*]octane-3-carboxylic Acid Methyl Ester

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

The named was prepared as follows. A slurry of 4-amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one (340 mg, 0.89 mmol), tricycle[3.2.1.0*2,4*]oct-6-ene-3-carboxylic acid ethyl ester (240 mg, 1.35 mmol), tetrabutylammonium iodide (67 mg, 0.18 mmol), piperidine (230 mg, 2.7 mmol), formic acid (170 mg, 0.14 mmol) and dichlorobis(acetonitrile) palladium(II) (23 mg, 0.09 mmol) in DMF (0.36 mL) was stirred at 125° C. for 16 hours. The reaction mixture was cooled, diluted into EtOAc, washed with water, saturated aqueous brine, dried over magnesium sulfate and concentrated in vacuo to afford an oil. Chromatography (20 g of silica gel, 1-5% methanol:chloroform) afforded a solid, 127 mg. IC50 78.3 nM.

Aufarbeitung

  1. customThe named was prepared
  2. temperatureThe reaction mixture was cooled
  3. washwashed with water, saturated aqueous brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford an oil

Quellen und Nachweise

ORD-Eintrag
ord-4c9057a628154627ba342972ca859969
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07718645B2

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