Toluene → 5-Methyl-4-oxo-3,4,5,7-tetrahydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester

HRID 45093Notes

Reaction equation

HRID 45093 reaction equation
[H-].[Na+].C(O[C:6](=O)[CH2:7][NH:8][C:9]([O:11]CC)=[O:10])C.C(O[C:18](=[O:22])[CH:19]=[CH:20][CH3:21])C.C(O)(=O)C.[CH:27]([NH2:29])=[NH:28].[O-]CC.[Na+].[C:34]1([CH3:40])[CH:39]=CC=C[CH:35]=1>C(O)C>[C:34]([O:11][C:9]([N:8]1[CH:20]([CH3:21])[C:19]2[C:18](=[O:22])[NH:29][CH:27]=[N:28][C:6]=2[CH2:7]1)=[O:10])([CH3:35])([CH3:39])[CH3:40]

Participants

8

Reactant 6

HCID 1140TolueneHCID 121912-Butenoic acid, ethyl esterHCID 24758Sodium hydrideHCID 160693Formamidine acetateHCID 226277Ethyl 2-(ethoxycarbonylamino)acetateHCID 2723922Sodium ethoxide

Product 1

HCID 1361587835-Methyl-4-oxo-3,4,5,7-tetrahydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of NaH (9.72 g, 243 mmol, 60% in mineral oil) in toluene (100 mL), ethoxycarbonylamino-acetic acid ethyl ester (38 g, 187 mmol) is added at 0° C. The reaction is left stirring for 5 h at the same temperature. At that point but-2-enoic acid ethyl ester (25.6 g, 224 mmol) is added and the reaction allowed to warm up to rt and stirred for further 2 h. Ethanol (30 mL) is added and the reaction is then evaporated. The crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL), then formamidine acetate (343 g, 1189 mmol) is added followed by sodium ethoxide (47.2 g, 694 mmol). The reaction is left stirring at 90° C. for 8 h. The solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL) is added followed by DCM (1 L). The water layer is extracted two times with DCM. The organics are dried and evaporate. The crude product is separated by FCC (DCM/MeOH 100:0 to 90:10) to give the title compound. MS (ESI) m/z 252.2 (M+1).

Workup

  1. additionis added at 0° C
  2. waitThe reaction is left
  3. stirringstirred for further 2 h
  4. customthe reaction is then evaporated
  5. dissolutionThe crude 1-tert-butyl 3-ethyl 2-methyl-4-oxopyrrolidine-1,3-dicarboxylate is dissolved in EtOH (1500 mL)
  6. waitThe reaction is left
  7. stirringstirring at 90° C. for 8 h
  8. customThe solvent is then removed and to the crude material a saturated solution of NH4Cl (200 mL)
  9. additionis added
  10. extractionThe water layer is extracted two times with DCM
  11. customThe organics are dried
  12. customevaporate
  13. customThe crude product is separated by FCC (DCM/MeOH 100:0 to 90:10)

Sources & evidence

ORD record
ord-bb0e059979604169a0d95b126f391311
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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