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Formamide → Ethyl 4-oxo-3,4,5,7-tetrahydro-6H-pyrrolo[3',4':4,5]thieno[2,3-d]pyrimidine-6-carboxylate

HRID 38521
Notes
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Reaction equation

HRID 38521 reaction equation
[NH2:1][C:2]1[S:14][C:5]2[CH2:6][N:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:8][C:4]=2[C:3]=1[C:15]([O:17]CC)=O.C([O-])=O.[NH4+].[CH:24]([NH2:26])=O>O>[O:17]=[C:15]1[NH:26][CH:24]=[N:1][C:2]2[S:14][C:5]3[CH2:6][N:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:8][C:4]=3[C:3]1=2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 713FormamideHCID 2723923Ammonium formateHCID 22464559Diethyl 2-amino-4,6-dihydro-5H-thieno[2,3-c]pyrrole-3,5-dicarboxylate

Product 1

HCID 58116983Ethyl 4-oxo-3,4,5,7-tetrahydro-6H-pyrrolo[3',4':4,5]thieno[2,3-d]pyrimidine-6-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

Diethyl 2-amino-4,6-dihydro-5H-thieno[2,3-c]pyrrole-3,5-dicarboxylate from Example 19A (3.60 g, 12.7 mmol) was dissolved in formamide (72 mL), and ammonium formiate (2.11 g, 20.3 mmol) was added. The mixture was heated to 140° C. overnight, then diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The precipitate in the aqueous layer was collected by suction filtration and combined with the organic extracts. The product was purified by column chromatography on silica gel (eluent: DCM/MeOH 100:3) and subsequently triturated with tert-butyl methyl ether to yield 1.74 g (52%) of the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customthe solvent was removed in vacuo
  4. filtrationThe precipitate in the aqueous layer was collected by suction filtration
  5. customThe product was purified by column chromatography on silica gel (eluent: DCM/MeOH 100:3)
  6. customsubsequently triturated with tert-butyl methyl ether

Sources & evidence

ORD record
ord-8f196d1a7e684c90ac905bf95ac8b7f5
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08524722B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes