Acetyl chloride → 2,5,6,7-Tetramethyl-3H,4H,5H-pyrrolo[3,2-d]pyrimidin-4-one

HRID 1772178Notes

Reaction equation

HRID 1772178 reaction equation
[C:1](Cl)(=O)C.[NH2:5][C:6]1[C:10]([CH3:11])=[C:9]([CH3:12])[NH:8][C:7]=1[C:13]([O:15]C)=O.[CH3:17][CH2:18][N:19](C(C)C)C(C)C.C([O-])(O)=O.[Na+].[OH-].[Na+].COS(OC)(=O)=O>[Br-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O.C(Cl)Cl>[CH3:17][C:18]1[NH:19][C:13](=[O:15])[C:7]2[N:8]([CH3:1])[C:9]([CH3:12])=[C:10]([CH3:11])[C:6]=2[N:5]=1

Participants

10

Reactant 6

HCID 6367Acetyl chlorideHCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 117903148Methyl 3-amino-4,5-dimethyl-1H-pyrrole-2-carboxylate

Product 1

HCID 1360300782,5,6,7-Tetramethyl-3H,4H,5H-pyrrolo[3,2-d]pyrimidin-4-one

Reagents, catalysts & solvents 3

HCID 165294Benzyltriethylammonium bromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Acetyl chloride (1 mol/l in DCM, 13 ml, 13 mmol) is added to a mixture of methyl 3-amino-4,5-dimethyl-1H-pyrrole-2-carboxylate N9a (2.2 g, 12.1 mmol), DIPEA (4.5 ml, 26.5 mmol) and DCM (40 ml) at 0° C. under stirring. The mixture is warmed to RT and stirring continued for 1 hour. Saturated aqueous solution of NaHCO3 is added and the precipitate collected. The aqueous phase is extracted with DCM. The combined organic layers are dried over MgSO4, concentrated in vacuo and pooled with the precipitate. DCM (35 ml) and benzyltriethylammonium bromide (645 mg, 2.37 mmol) is added and the mixture cooled to 0° C. Sodium hydroxide (50% in water, 15 ml) and dimethylsulfate (1.4 g, 11.2 mmol) is added and stirring continued at 0° C. for 1 hour. Water is added and the mixture extracted with DCM. The combined organic layers are dried over MgSO4 and concentrated in vacuo. Concentrated aqueous ammonia (20 ml) is added and the mixture heated to 100° C. in a microwave for 30 hours. The mixture is concentrated in vacuo and the crude product (0.59 g) used without further purification. HPLC-MS: M+H=192; tR=0.62 min (METHOD—1).

Workup

  1. stirringstirring
  2. customthe precipitate collected
  3. extractionThe aqueous phase is extracted with DCM
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. temperaturethe mixture cooled to 0° C
  7. stirringstirring
  8. waitcontinued at 0° C. for 1 hour
  9. extractionthe mixture extracted with DCM
  10. dry with materialThe combined organic layers are dried over MgSO4
  11. concentrationconcentrated in vacuo
  12. additionConcentrated aqueous ammonia (20 ml) is added
  13. temperaturethe mixture heated to 100° C. in a microwave for 30 hours
  14. concentrationThe mixture is concentrated in vacuo
  15. customthe crude product (0.59 g) used without further purification

Sources & evidence

ORD record
ord-5137a9c3d8c6401eaf03905f9f873268
Source dataset
uspto-grants-2016_02
Patent number
US09249151B2

Reaction notes

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