Cyclobutanone → HCID 11842670, Verbindung

HRID 549233Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 549233
[CH3:1][C:2]1[N:3]([CH2:30][CH2:31][CH3:32])[N:4]=[C:5]2[C:14]=1[C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:7]=[C:6]2[N:15](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O.C([Li])(C)(C)C.[C:38]1(=[O:42])[CH2:41][CH2:40][CH2:39]1.[Cl-].[NH4+]>O1CCCC1.CCCCC>[NH2:15][C:6]1[C:5]2=[N:4][N:3]([CH2:30][CH2:31][CH3:32])[C:2]([CH2:1][C:38]3([OH:42])[CH2:41][CH2:40][CH2:39]3)=[C:14]2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1

Komponenten

7

Edukt 4

HCID 14496CyclobutanoneHCID 25517Ammonium ChlorideHCID 67157595HCID 67157595, VerbindungHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 11842670HCID 11842670, VerbindungAusbeute 31,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8003PentaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of di(tert-butyl) 1-methyl-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (1.32 g, 3.00 mmol) in anhydrous tetrahydrofuran (THF) (30 mL) was cooled to −78° C. under an argon atmosphere. tert-Butyllithium (7.06 mL of a 1.7 M solution in pentane) was added over a period of eight minutes, and the resulting dark-colored solution was stirred at −78° C. for 40 minutes. Cyclobutanone (1.05 g, 15 mmol) was added over a period of two minutes, and the −78° C. bath was replaced with a 0° C. bath. The reaction mixture was stirred for 10 minutes, and then saturated aqueous ammonium chloride (30 mL) was added. The aqueous layer was separated and extracted three times with tert-butyl methyl ether, and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.3 g) was purified by automated flash chromatography and then boiled in 2 M hydrochloric acid for 30 minutes. The solution was allowed to cool to room temperature overnight and then made basic with the addition of 2 M aqueous sodium carbonate. The resulting solution was extracted four times with chloroform, and the combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.2 g) was purified twice by automated flash chromatography and recrystallized from acetonitrile to provide 297 mg of 1-[(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)methyl]cyclobutanol as a white solid, mp 191-193° C.

Aufarbeitung

  1. customthe −78° C. bath
  2. customwas replaced with a 0° C.
  3. stirringThe reaction mixture was stirred for 10 minutes
  4. customThe aqueous layer was separated
  5. extractionextracted three times with tert-butyl methyl ether
  6. dry with materialthe combined organic fractions were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue (1.3 g) was purified by automated flash chromatography
  10. waitboiled in 2 M hydrochloric acid for 30 minutes
  11. temperatureto cool to room temperature overnight
  12. additionmade basic with the addition of 2 M aqueous sodium carbonate
  13. extractionThe resulting solution was extracted four times with chloroform
  14. dry with materialthe combined extracts were dried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure
  17. customThe residue (1.2 g) was purified twice by automated flash chromatography
  18. customrecrystallized from acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-b6c01dcecf0c4c02a21486136a1b7127
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07943636B2

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