Phosphate → N-methoxy-N-methyl-2-bromoimidazo[5,1-b]thiazole-7-carboxamide

HRID 1444197Notes

Reaction equation

HRID 1444197 reaction equation
[Cl-].C([Al+]CC)C.Cl.[CH3:8][NH:9][O:10][CH3:11].[Br:12][C:13]1[S:17][C:16]2=[C:18]([C:21]([O:23]CC)=O)[N:19]=[CH:20][N:15]2[CH:14]=1.P([O-])([O-])([O-])=O>ClCCl>[CH3:11][O:10][N:9]([CH3:8])[C:21]([C:18]1[N:19]=[CH:20][N:15]2[CH:14]=[C:13]([Br:12])[S:17][C:16]=12)=[O:23]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 16686102Diethyl aluminum chlorideHCID 59168405Ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate

Product 1

HCID 59168398N-methoxy-N-methyl-2-bromoimidazo[5,1-b]thiazole-7-carboxamideYield 92.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diethylaluminum chloride (0.9 M hexane solution; 2.3 ml, 2.11 mmol) was added to an ice cooled solution of N,O-dimethylhydroxylamine hydrochloride (206 mg, 2.11 mmol) in dichloromethane (8 ml), and, while gradually raising the temperature, the mixture was stirred for one hr. A solution of ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate (116 mg, 0.42 mmol) in dichloromethane (4 ml) was added and stirred at room temperature for 15 hr. A phosphate buffer solution (10 ml) was added to the reaction solution, and the mixture was stirred at room temperature for 10 min and was filtered through Celite. The filtrate was washed with saturated brine and was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=30:1→10:1) to give N-methoxy-N-methyl-2-bromoimidazo[5,1-b]thiazole-7-carboxamide (113 mg, 92%) as a white solid.

Workup

  1. temperaturewhile gradually raising the temperature
  2. stirringstirred at room temperature for 15 hr
  3. stirringthe mixture was stirred at room temperature for 10 min
  4. filtrationwas filtered through Celite
  5. washThe filtrate was washed with saturated brine
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. customthe solvent was removed by distillation under the reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (ethyl acetate:methanol=30:1→10:1)

Sources & evidence

ORD record
ord-28d3e3d5dad04d23835b2a82ba164087
Source dataset
uspto-grants-2010_02
Patent number
US07662841B2

Reaction notes

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