Formaldehyde → 6-(Ethoxymethyl-amino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

HRID 2080216Notes

Reaction equation

HRID 2080216 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([NH:8][CH2:9][C:10]2[S:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[O:7])=[CH:4][N:3]=1.C=O.O.[C:27]([O:30][CH2:31]C)(=O)[CH3:28]>C(O)C>[CH2:27]([O:30][CH2:31][NH:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([NH:8][CH2:9][C:10]2[S:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[O:7])=[CH:4][N:3]=1)[CH3:28]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 8857Ethyl AcetateHCID 231305396-Amino-N-(5-phenoxy thiophen-2-ylmethyl)-nicotinamide

Product 1

HCID 231303456-(Ethoxymethyl-amino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamideYield 66.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 6-amino-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-138 (600 mg, 1.8 mmol) in ethanol (40 mL) were added 5,5-dimethylimidazo phospho-2,4-dione (260 mg, 2.0 mmol) and 37% formaldehyde aqueous solution (3 mL), and the solution was stirred under reflux for 30 minutes. Water and ethyl acetate were added to the reaction solution, which was then partitioned, and the organic layer was washed with water twice. NH silica gel was added to the organic layer, the solvent was evaporated in vacuo for adsorption, purification was carried out by NH silica gel column chromatography (ethyl acetate), and the title compound (457 mg, 1.19 mmol, 66.1%) was obtained as a white solid.

Workup

  1. temperatureunder reflux for 30 minutes
  2. customwas then partitioned
  3. washthe organic layer was washed with water twice
  4. additionNH silica gel was added to the organic layer
  5. customthe solvent was evaporated in vacuo for adsorption, purification

Sources & evidence

ORD record
ord-11150e20e3e34ac6920922d18ceb38d8
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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