3,4-Dichloroaniline → Ethyl 4-[(3,4-dichlorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]furo[2,3-d]pyrimidine-7(6H)carboxylate

HRID 38535Notes

Reaction equation

HRID 38535 reaction equation
[C:1]([C:3]1[C:11]2[CH2:10][CH2:9][N:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:7][C:6]=2[O:5][C:4]=1/[N:17]=[CH:18]/[N:19](C)C)#[N:2].[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[Cl:30])N>C(#N)C.C(O)(=O)C>[Cl:22][C:23]1[CH:24]=[C:25]([NH:2][C:1]2[C:3]3[C:11]4[CH2:10][CH2:9][N:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:7][C:6]=4[O:5][C:4]=3[N:17]=[CH:18][N:19]=2)[CH:27]=[CH:28][C:29]=1[Cl:30]

Participants

5

Reactant 2

HCID 72573,4-DichloroanilineHCID 58116902ethyl 3-cyano-2-[(E)-dimethylaminomethylideneamino]-5,7-dihydro-4H-furo[2,3-c]pyridine-6-carboxylate

Product 1

HCID 58116915Ethyl 4-[(3,4-dichlorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]furo[2,3-d]pyrimidine-7(6H)carboxylateYield 34%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

Ethyl 3-cyano-2-{[(1E)-(dimethylamino)methylidene]amino}-4,7-dihydrofuro[2,3-c]pyridine-6(5H)-carboxylate from Example 37A (1.00 g, 4.14 mmol) and 3,4-dichloroaniline (1.12 g, 6.89 mmol) were heated in a mixture of acetonitrile (20 mL) and acetic acid (2 mL) for 20 h under reflux. The mixture was then half-concentrated in vacuo and heated for further 20 h. Subsequently, it was diluted with water, basified with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated. The residue was triturated with methanol. The precipitate was collected by suction filtration to yield 542 mg (34%) of the title compound. A second batch of 50 mg (4%) was obtained from the mother liquor after purification by preparative HPLC.

Workup

  1. temperatureunder reflux
  2. concentrationThe mixture was then half-concentrated in vacuo
  3. temperatureheated for further 20 h
  4. additionSubsequently, it was diluted with water
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was triturated with methanol
  9. filtrationThe precipitate was collected by suction filtration

Sources & evidence

ORD record
ord-f007c0d757fc43bb98ada258730d6228
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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