Dimethylformamide dimethyl acetal → 5-Bromo-3-(dimethylaminomethyleneamino)thiophene-2-carboxylic acid methyl ester

HRID 1916357Notes

Reaction equation

HRID 1916357 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH2:10]C)=[O:8])=[C:4]([NH2:12])[CH:3]=1.CO[CH:15](OC)[N:16]([CH3:18])[CH3:17]>CCO>[Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([N:12]=[CH:15][N:16]([CH3:18])[CH3:17])[CH:3]=1

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 67066667Ethyl 3-amino-5-bromothiophene-2-carboxylate

Product 1

HCID 600270405-Bromo-3-(dimethylaminomethyleneamino)thiophene-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of ethyl 5-bromo-3-amino-2-thiophenecarboxylate (1.0 g, 4.2 mmol) and dimethylformamide dimethylacetal (1.1 mL, 8.5 mmol) in EtOH (30 mL). was heated to reflux for 50 min. After cooling, the solvent was removed in vacuo. The residue was coevaporated with toluene (2×20 mL) to yield methyl 5-bromo-3-(((dimethylamino)methylene)amino)-2-thiophenecarboxylate. The residue and 1-((4-amino-2-methoxy)phenoxy)-2-methyl-2-propanol (0.90 mg, 4.2 mmol) (described in Part B of Example 82) were mixed with phenol (4 g) prior to heating at 130° C. for 40 min. After cooling, the mixture was chromatographed (120 g silica, CH2Cl2 to 50% EtOAc-CH2Cl2) to provide 1-(4-(6-bromo-4-oxo-thieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methyl-2-propanol as a tan solid (1.2 g, 67%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 50 min
  3. temperatureAfter cooling
  4. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-88411902217d4d4281a07e1808e31c45
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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