Potassium Carbonate → HCID 57785964, Verbindung

HRID 1398988Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398988
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:16]([CH2:17][CH2:18][CH2:19][C:20](OCC)=O)[C:15]2[C:25]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:26][CH:27]=[CH:28][C:14]=2[N:13]=1.[BH4-].[Li+].CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.N1C=CC=CC=1.CN(C)C=O.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[N:11]1[C:12]2=[N:13][C:14]3[CH:28]=[CH:27][CH:26]=[C:25]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])[C:15]=3[N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]1

Komponenten

9

Edukt 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 4148881Lithium borohydrideHCID 68763470Ethyl 4-[2-[(2,4-dimethoxyphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Produkt 1

HCID 57785964HCID 57785964, VerbindungAusbeute 29,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of ethyl 4-[2-[(2,4-dimethoxyphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 56; 569.3 mg, 1.26 mmol) in tetrahydrofuran (5.0 mL) was added lithium borohydride (82.0 mg, 3.77 mmol) at 0° C. The reaction mixture was stirred at 60° C. for 1.5 hr. After cooling, the reaction mixture was quenched with water at 0° C. and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting crude butanol (MS Calcd.: 411; Found: 412 (M+H)) was subjected for the next step without further purification. To a solution of the crude material in pyridine (1.0 mL) was added methanesulfonyl chloride (490 μL, 6.28 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hr. The reaction mixture was quenched with aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude mesylate was subjected for the next step without further purification. To the crude material (MS Calcd.: 489; Found: 490 (M+H)) in N,N-dimethylformamide (1.0 mL) was added potassium carbonate (346.9 mg, 2.51 mmol). The reaction mixture was stirred at 60° C. for 19 hr. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-40% ethyl acetate/n-hexane gradient mixture. The resulting solid was washed with n-hexane to give the title compound as a colorless powder (144.5 mg, 0.367 mmol, 29%).

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe reaction mixture was quenched with water at 0° C.
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude butanol (MS Calcd.: 411; Found: 412 (M+H)) was subjected for the next step without further purification
  9. stirringThe reaction mixture was stirred at room temperature for 2 hr
  10. customThe reaction mixture was quenched with aqueous sodium hydrogen carbonate
  11. extractionextracted with ethyl acetate (×3)
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe crude mesylate was subjected for the next step without further purification
  17. stirringThe reaction mixture was stirred at 60° C. for 19 hr
  18. temperatureAfter cooling
  19. extractionextracted with ethyl acetate (×3)
  20. washThe combined organic layer was washed with water (×2) and brine
  21. dry with materialdried over anhydrous magnesium sulfate
  22. filtrationfiltered
  23. concentrationconcentrated in vacuo
  24. customThe residue was purified by silica gel column chromatography
  25. washeluting with a 10-40% ethyl acetate/n-hexane gradient mixture
  26. washThe resulting solid was washed with n-hexane

Quellen und Nachweise

ORD-Eintrag
ord-0bd625ef0ee1456a8ec0a6224496df95
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901141B2

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