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

HRID 905866Notes

Reaction equation

HRID 905866 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]([CH3:21])[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][C:13]2[NH:16][CH:17]=[C:18]([CH3:19])[C:12]=2[C:11]1=[O:20].O.[OH-].[Na+].CN(C)[CH:27]=[O:28]>>[CH3:21][N:7]([CH3:6])[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][C:13]2[NH:16][C:17]([CH:27]=[O:28])=[C:18]([CH3:19])[C:12]=2[C:11]1=[O:20]

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 666085465-(2-Dimethylamino-ethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one

Product 1

HCID 866376895-(2-dimethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehydeYield 38%

Conditions

Temperature
0 °C

Procedure

A stirred solution of N,N-dimethylformamide (2 ml) was added dropwise slowly with phosphorus oxychloride (104 μl, 1.1 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 5-(2-dimethylamino-ethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (221 mg, 1 mmol) in 1.2 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 (15 ml), 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 triethylamine:methanol:dichloromethane (1:20:500) as eluents to give 5-(2-dimethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde (105 mg, 38%) as a pink oil which was used as such.

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 triethylamine:methanol:dichloromethane (1:20:500) as eluents

Sources & evidence

ORD record
ord-6d8a4ca8724a4dfcb2104bf5b0d51872
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Reaction notes

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