N,N-Diethylaniline → 4-Chloro-5-mesityl-7-methyl-N,N-dipropyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 598130Notes

Reaction equation

HRID 598130 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=O)[C:5]2[C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[CH3:19])=[CH:9][N:8]([CH3:20])[C:6]=2[N:7]=1.C(N(CC)[C:25]1[CH:30]=[CH:29]C=CC=1)C.P(Cl)(Cl)([Cl:35])=O.[H-].[Na+].[CH2:40](I)[CH2:41][CH3:42]>O.CN(C)C=O>[Cl:35][C:4]1[C:5]2[C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[CH3:19])=[CH:9][N:8]([CH3:20])[C:6]=2[N:7]=[C:2]([N:1]([CH2:25][CH2:30][CH3:29])[CH2:40][CH2:41][CH3:42])[N:3]=1

Participants

8

Reactant 5

HCID 7061N,N-DiethylanilineHCID 24758Sodium hydrideHCID 24813Phosphorus oxychlorideHCID 336431-IodopropaneHCID 1364007122-Amino-5-mesityl-7-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

Product 1

HCID 545799764-Chloro-5-mesityl-7-methyl-N,N-dipropyl-7H-pyrrolo[2,3-d]pyrimidin-2-amineYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-5-mesityl-7-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (142 mg, 0.50 mmol), N,N-diethylaniline (68 mg, 0.50 mmol), and phosphorus oxychloride (10 ml) was heated at 80° C. with stirring for 4 hours. The dark orange solution was allowed to cool to room temperature and concentrated in vacuo. Water (10 ml) was then added to the residue at 0° C. with vigorous stirring. Concentrated aqueous ammonium hydroxide was added and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. To a mixture of the residue and dimethylformamide (5 ml) was added sodium hydride (60% in oil, 50 mg, 1.25 mmol) at 0° C. and stirred for 0.5 hour. After stirring at room temperature for 0.5 hour, to the mixture was added a solution of n-PrI (213 mg, 1.25 mmol) and dimethylformamide (2 ml) at 0° C. and stirred for 0.5 hour. After stirring at room temperature for 1 hour, the mixture was diluted with water (20 ml) and extracted with ethyl acetate (50 ml×2). The extracts were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (20:1) to give 59 mg (31%) of the title compound.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated in vacuo
  3. additionWater (10 ml) was then added to the residue at 0° C. with vigorous stirring
  4. additionConcentrated aqueous ammonium hydroxide was added
  5. extractionextracted with ethyl acetate (100 ml×2)
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. additionTo a mixture of the residue and dimethylformamide (5 ml)
  10. stirringstirred for 0.5 hour
  11. stirringAfter stirring at room temperature for 0.5 hour, to the mixture
  12. stirringstirred for 0.5 hour
  13. stirringAfter stirring at room temperature for 1 hour
  14. extractionextracted with ethyl acetate (50 ml×2)
  15. washwashed with brine
  16. dry with materialdried over sodium sulfate
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by silica gel chromatography
  19. washeluting with hexane/ethyl acetate (20:1)

Sources & evidence

ORD record
ord-857e3a34823648dc9ddbdf5c5b0f2cf9
Source dataset
uspto-grants-2011_03
Patent number
US07897607B2

Reaction notes

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