Benzaldehyde → 2-phenyl-6-(pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2363925Notes

Reaction equation

HRID 2363925 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([NH2:15])=[O:14].O.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20](S(O)(=O)=O)=[CH:19][CH:18]=1.C(=O)C1C=CC=CC=1.C1(C)C=CC=CC=1>CC(O)=O>[C:17]1([CH:27]2[NH:1][C:2]3[CH:6]=[C:5]([C:7]4[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=4)[S:4][C:3]=3[C:13](=[O:14])[NH:15]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 99208523-Amino-5-(pyridin-4-yl)thiophene-2-carboxamide

Product 1

HCID 667432022-phenyl-6-(pyridin-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 28.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3-amino-5-(pyridin-4-yl)thiophene-2-carboxamide (99.9 mg, 0.456 mmol), p-toluenesulfonic acid monohydrate (8.67 mg, 0.046 mmol), benzaldehyde (0.056 mL, 0.547 mmol) and toluene (5 mL) was refluxed for 2 h. The reaction didn't occur. After cooling, AcOH (3 mL) was added, and the mixture was refluxed for 3 h. The reaction mixture was concentrated in vacuo. The residue was suspended in DMSO (3 mL) and the insoluble materials were filtered off. The filtrate was purified by preparative HPLC (ODS column, 0.1% TFA, water-MeCN=95:5-0:100). The fractions containing the object were basified by sat. aqueous sodium hydrogen carbonate, and the organic materials were extracted with EtOAc. The organic layer was dried over magnesium sulfate and concentrated in vacuo to afford the title compound (4.0 mg, yield 2.86%) as a yellow solid:

Workup

  1. temperaturewas refluxed for 2 h
  2. customThe reaction
  3. temperatureAfter cooling
  4. temperaturethe mixture was refluxed for 3 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. filtrationthe insoluble materials were filtered off
  7. customThe filtrate was purified by preparative HPLC (ODS column, 0.1% TFA, water-MeCN=95:5-0:100)
  8. additionThe fractions containing the object
  9. extractionthe organic materials were extracted with EtOAc
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0c66a374bf1640fd8a091294cea40fd9
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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