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

HRID 2365006Notes

Reaction equation

HRID 2365006 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[C:11]2[C:12](=[O:24])[N:13]([CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH2:14][CH2:15][C:10]=2[NH:9][CH:8]=1.O.[OH-].[Na+].CN(C)[CH:30]=[O:31]>>[CH3:6][C:7]1[C:11]2[C:12](=[O:24])[N:13]([CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[CH2:14][CH2:15][C:10]=2[NH:9][C:8]=1[CH:30]=[O:31]

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 666073783-methyl-5-(2-morpholin-4-yl-ethyl)-1,5,6,7-tetrahydro-Pyrrolo[3,2-c]pyridin-4-one

Product 1

HCID 866376763-methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehydeYield 17.5%

Conditions

Temperature
0 °C

Procedure

N,N-dimethylformamide (1.68 ml) was added dropwise slowly with phosphorus oxychloride (0.9 ml, 9.65 mmol) under an argon atmosphere while maintaining the temperature at 0° C. Upon completion of the addition, the mixture was stirred for 15 minutes at room temperature and cooled down to 0˜5° C. in an ice-water bath. A mixture of 3-methyl-5-(2-morpholin-4-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (2.31 g, 8.77 mmol) in 10.5 ml of N,N-dimethylformamide was added dropwise to the above solution. Upon completion of the addition, the mixture was stirred for 2 hours at 0° C., added with cold water (5 ml) and stirred for 5 minutes. The resulting mixture was adjusted to pH 12 with 10% aqueous sodium hydroxide solution and extracted with dichloromethane (15 ml×6). The combined organic extracts were washed with brine (15 ml), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane:methanol (10:1) as eluents to give 3-methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde (550 mg, 17.5%) as a red oil.

Workup

  1. additionUpon completion of the addition
  2. temperaturecooled down to 0˜5° C. in an ice-water bath
  3. additionwas added dropwise to the above solution
  4. additionUpon completion of the addition
  5. stirringthe mixture was stirred for 2 hours at 0° C.
  6. stirringstirred for 5 minutes
  7. extractionextracted with dichloromethane (15 ml×6)
  8. washThe combined organic extracts were washed with brine (15 ml)
  9. dry with materialdried with anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography with dichloromethane:methanol (10:1) as eluents

Sources & evidence

ORD record
ord-9cd6f4dbe2404361a79c80119d441f0e
Source dataset
uspto-grants-2014_04
Patent number
US08697692B2

Reaction notes

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