Dimethylformamide → (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde

HRID 2068727Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2068727
P(Cl)(Cl)(Cl)=O.CN(C)[CH:8]=[O:9].[OH:11][C@@H:12]([CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[CH2:13][N:14]1[CH2:19][CH2:18][C:17]2[NH:20][CH:21]=[C:22]([CH3:23])[C:16]=2[C:15]1=[O:24]>ClCCl>[OH:11][C@@H:12]([CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[CH2:13][N:14]1[CH2:19][CH2:18][C:17]2[NH:20][C:21]([CH:8]=[O:9])=[C:22]([CH3:23])[C:16]=2[C:15]1=[O:24]

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 59375984(S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one

Produkt 1

HCID 59375986(S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehydeAusbeute 78,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Phosphorus oxychloride (500 μL, 1.3 mmol) and N,N-dimethylformamide (704 μL, 9 mmol) were dissolved in 15 mL of anhydrous dichloromethane under stirring at room temperature, and the reaction solution was stirring for 15 minutes while maintaining the temperature at −10° C. in an ice-water bath. (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 5e (586 mg, 2 mmol) was dissolved in 8 mL of dichloromethane under stirring, and the solution was then added dropwise to the above reaction system. Upon completion of the addition, the ice-water bath was removed. The reaction system was allowed to warm up to room temperature and stirred for another 2 hours. The reaction was completed until TLC showed the disappearance of starting materials. The reaction mixture was quenched with iced water and stirred for 15 minutes. The mixture was adjusted to pH about 12 with 10N sodium hydroxide solution. The mixture was extracted with the solvent mixture of dichloromethane and methanol (V:V=20:1, 100 mL ×5). The combined organic extracts were washed with saturated brine (100 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde 5f (490 mg, yield 78.8%) as a white solid.

Aufarbeitung

  1. stirringthe reaction solution was stirring for 15 minutes
  2. temperaturewhile maintaining the temperature at −10° C. in an ice-water bath
  3. stirringunder stirring
  4. additionthe solution was then added dropwise to the above reaction system
  5. additionUpon completion of the addition
  6. customthe ice-water bath was removed
  7. temperatureto warm up to room temperature
  8. stirringstirred for another 2 hours
  9. customThe reaction mixture was quenched with iced water
  10. stirringstirred for 15 minutes
  11. extractionThe mixture was extracted with the solvent mixture of dichloromethane and methanol (V:V=20:1, 100 mL ×5)
  12. washThe combined organic extracts were washed with saturated brine (100 mL)
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. customto remove the drying agent
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c43dc134abda42a88e95dd2391de2280
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299069B2

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