Tetrahydrofuran → [9-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanol

HRID 1399099Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1399099
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:31]([O:33]C)=O)=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:20]3[C:21]([O:29][CH3:30])=[N:22][C:23]([CH3:28])=[N:24][C:25]=3[O:26][CH3:27])[CH2:17][CH2:18][CH2:19][N:12]21.O1[CH2:39][CH2:38][CH2:37]C1>>[Cl:6][C:7]1[C:15]2[N:14]=[C:13]3[N:16]([C:20]4[C:25]([O:26][CH3:27])=[N:24][C:23]([CH3:28])=[N:22][C:21]=4[O:29][CH3:30])[CH2:17][CH2:18][CH2:19][N:12]3[C:11]=2[C:10]([C:31]([CH:37]2[CH2:38][CH2:39]2)([CH:1]2[CH2:3][CH2:2]2)[OH:33])=[CH:9][CH:8]=1

Komponenten

4

Edukt 3

HCID 8028TetrahydrofuranHCID 57785929Methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateHCID 178418630HCID 178418630, Verbindung

Produkt 1

HCID 57786189[9-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanolAusbeute 55 %

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Cyclopropylmagnesium bromide (1.0 M solution in tetrahydrofuran, 1.9 mL, 1.9 mmol) was added to a stirred solution of methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (159 mg, 0.381 mmol) in tetrahydrofuran (3.8 mL), and the mixture was stirred at 50° C. for 11 hr. The reaction was quenched by aqueous saturated ammonium chloride, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 15-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethanol/ethyl acetate to give the title compound as a colorless crystal (98.6 mg, 0.210 mmol, 55%).

Aufarbeitung

  1. customThe reaction was quenched by aqueous saturated ammonium chloride
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a 15-50% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give the solid, which
  10. customwas recrystallized from ethanol/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-a68a29ee8fa74be79daebe70f4c673bd
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901141B2

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