Ethyl Acetate → 2,2-Dimethyl-propionic acid 8-(4-acetylamino-benzyl)-3-butyl-1-(2-fluoro-5-nitro-benzyl)-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester

HRID 720625Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720625
[C:1]([NH:4][C:5]1[CH:34]=[CH:33][C:8]([CH2:9][C:10]2[N:18]([CH2:19][O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:17]3[C:16](=[O:27])[NH:15][C:14](=[O:28])[N:13]([CH2:29][CH2:30][CH2:31][CH3:32])[C:12]=3[N:11]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].N12CCCN=C1CCCCC2.Br[CH2:47][C:48]1[CH:53]=[C:52]([N+:54]([O-:56])=[O:55])[CH:51]=[CH:50][C:49]=1[F:57].C(OCC)(=O)C>C(#N)C>[C:1]([NH:4][C:5]1[CH:34]=[CH:33][C:8]([CH2:9][C:10]2[N:18]([CH2:19][O:20][C:21](=[O:26])[C:22]([CH3:24])([CH3:25])[CH3:23])[C:17]3[C:16](=[O:27])[N:15]([CH2:47][C:48]4[CH:53]=[C:52]([N+:54]([O-:56])=[O:55])[CH:51]=[CH:50][C:49]=4[F:57])[C:14](=[O:28])[N:13]([CH2:29][CH2:30][CH2:31][CH3:32])[C:12]=3[N:11]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 103539672-(Bromomethyl)-1-fluoro-4-nitrobenzeneHCID 587392662,2-Dimethyl-propionic acid 8-(4-acetylamino-benzyl)-3-butyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester

Produkt 1

HCID 587392302,2-Dimethyl-propionic acid 8-(4-acetylamino-benzyl)-3-butyl-1-(2-fluoro-5-nitro-benzyl)-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl esterAusbeute 33,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of 2,2-dimethyl-propionic acid 8-(4-acetylamino-benzyl)-3-butyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester (104 mg, 0.22 mmol) in acetonitrile (2.0 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (0.03 mL, 0.24 mmol) and 2-bromomethyl-1-fluoro-4-nitro-benzene (56.6 mg, 0.24 mmol). The resulting solution was heated to 50° C. for 6 h. At this time, another portion of 1,8-diazabicyclo[5.4.0]undec-7-ene (0.03 mL, 0.24 mmol) was added. The reaction was stirred at 25° C. for 18 h. At this time, the reaction was poured into ethyl acetate (200 mL) and was washed with a 1N aqueous hydrochloric acid solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1:1 ethyl acetate/petroleum ether) afforded 2,2-dimethyl-propionic acid 8-(4-acetylamino-benzyl)-3-butyl-1-(2-fluoro-5-nitro-benzyl)-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester (45.3 mg, 33%) as a tan solid: FAB-HRMS m/e calcd for C31H35N6O7F (M+H)+ 623.2630, found 623.2631.

Aufarbeitung

  1. washwas washed with a 1N aqueous hydrochloric acid solution (1×50 mL)
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-74afe72b8b6f4727a3c920dbf8d75301
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135475B2

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