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

HRID 1444196Notes

Reaction equation

HRID 1444196 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]C)=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 59168410Methyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate

Product 1

HCID 59168398N-methoxy-N-methyl-2-bromoimidazo[5,1-b]thiazole-7-carboxamideYield 88.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diethylaluminum chloride (0.9 M hexane solution; 1.1 ml, 1.07 mmol) was added to an ice cooled solution of N,O-dimethylhydroxylamine hydrochloride (104 mg, 1.07 mmol) in dichloromethane (4 ml), and, while gradually raising the temperature, the mixture was stirred for one hr. A solution of methyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate (56 mg, 0.21 mmol) in dichloromethane (6 ml) was added thereto, and the mixture was stirred at room temperature for 21 hr. A phosphate buffer solution (5 ml) was added to the reaction solution, and the mixture was stirred at room temperature for 10 min and was then filtered through Celite. The filtrate was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=60:1→10:1) to give N-methoxy-N-methyl-2-bromoimidazo[5,1-b]thiazole-7-carboxamide (54 mg, 88%) as a white solid.

Workup

  1. temperaturewhile gradually raising the temperature
  2. stirringthe mixture was stirred at room temperature for 21 hr
  3. stirringthe mixture was stirred at room temperature for 10 min
  4. filtrationwas then 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=60:1→10:1)

Sources & evidence

ORD record
ord-51c8e1cfb68f48589fbeeda3f466929b
Source dataset
uspto-grants-2010_02
Patent number
US07662841B2

Reaction notes

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