Dimethylformamide → HCID 59375987, compound

HRID 2068718Notes

Reaction equation

HRID 2068718 reaction equation
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]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 59375992HCID 59375992, compound

Product 1

HCID 59375987HCID 59375987, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus oxychloride (674 μL, 4.04 mmol) and N,N-dimethylformamide (963 μL, 12.32 mmol) were dissolved in 21.18 mL of dichloromethane under stirring at room temperature, and the reaction solution was stirred for 15 minutes while maintaining the temperature at −10° C. in an ice-water bath. (R)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 1e (790 mg, 2.7 mmol) was dissolved in 10 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, and 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, and the reaction system was quenched with iced water and stirred for 15 minutes. The mixture was adjusted to pH about 12 with 10N sodium hydroxide solution and extracted with the solvent mixture of dichloromethane and methanol (V:V=20:1, 100 mL ×8). The combined organic extracts were washed with saturated brine (150 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to give the crude product (800 mg). The crude product was purified by silica gel column chromatography to give the title compound (R)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde 1f (650 mg, yield 75%) as a white solid.

Workup

  1. stirringthe reaction solution was stirred 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 system was quenched with iced water
  10. stirringstirred for 15 minutes
  11. extractionextracted with the solvent mixture of dichloromethane and methanol (V:V=20:1, 100 mL ×8)
  12. washThe combined organic extracts were washed with saturated brine (150 mL)
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. customto remove the drying agent
  16. concentrationconcentrated under reduced pressure
  17. customto give the crude product (800 mg)
  18. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3d22a7eb65d140cfa3040f0f20099c4f
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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