Allyl chloroformate → 5-(N-[prop-1-en-3-yloxycarbonyl]amino)-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

HRID 610608Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 610608
[NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.Cl[C:25]([O:27][CH2:28][CH:29]=[CH2:30])=[O:26]>N1C=CC=CC=1>[CH2:30]=[CH:29][CH2:28][O:27][C:25]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)=[O:26]

Komponenten

4

Edukt 2

HCID 18052Allyl chloroformate2×HCID 117268345-Amino-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

Produkt 1

HCID 196015485-(N-[prop-1-en-3-yloxycarbonyl]amino)-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 4.0 gm (12.6 mMol) 5-amino-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 2.7 mL (25.2 mMol) allyl chloroformate in 200 mL pyridine was heated at 50° C. for 5 hours. At this point an additional 2 mL of allyl chloroformate were added and heating was continued for another 1.5 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue partitioned between 1N sodium hydroxide and chloroform. The phases were separated and the aqueous phase was extracted well with chloroform. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. This residue was dissolved in 2M ammonia in methanol for two hours. The reaction mixture was concentrated under reduced pressure and the residue subjected to flash silica gel chromatography, eluting with dichloromethane containing from 2-5% methanol and 1% ammonium hydroxide. Fractions containing produce were combined and concentrated under reduced pressure. The residue was crystallized from aqueous ethanol to provide 2.9 gm (60%) 5-(N-[prop-1-en-3-yloxycarbonyl]amino)-3-(1-tert-butoxycarbonylpiperidin-4-yl)pyrrolo[3,2-b]pyridine. MS(m/e): 400(M+) Calculated for C21H28N4O4 : Theory: C, 62.98; H, 7.05; N, 13.99. Found: C, 63.06; H, 7.20; N, 14.11.

Aufarbeitung

  1. temperatureheating
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe resulting residue partitioned between 1N sodium hydroxide and chloroform
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted well with chloroform
  6. washwashed with saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThis residue was dissolved in 2M ammonia in methanol for two hours
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. washeluting with dichloromethane containing from 2-5% methanol and 1% ammonium hydroxide
  12. additionFractions containing
  13. customproduce
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was crystallized from aqueous ethanol

Quellen und Nachweise

ORD-Eintrag
ord-13fbd78855a64f40a44320ae8a190782
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US05998622

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