Dimethylformamide → N-(3-{[2-(acetylamino)-7-cyano-1,3-benzothiazol-6-yl]oxy}phenyl)-2-(3-bromophenyl)-2-methylpropanamide

HRID 1097462

Reaction equation

HRID 1097462 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:25][C:26]1[CH:27]=[C:28]([CH:45]=[CH:46][CH:47]=1)[O:29][C:30]1[CH:42]=[CH:41][C:33]2[N:34]=[C:35]([NH:37][C:38](=[O:40])[CH3:39])[S:36][C:32]=2[C:31]=1[C:43]#[N:44]>O1CCCC1.C(OCC)(=O)C>[C:38]([NH:37][C:35]1[S:36][C:32]2[C:31]([C:43]#[N:44])=[C:30]([O:29][C:28]3[CH:27]=[C:26]([NH:25][C:9](=[O:11])[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=4)([CH3:13])[CH3:12])[CH:47]=[CH:46][CH:45]=3)[CH:42]=[CH:41][C:33]=2[N:34]=1)(=[O:40])[CH3:39]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 128051282-(3-Bromophenyl)-2-methylpropanoic acidHCID 86644686N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]acetamide

Product 1

HCID 59454477N-(3-{[2-(acetylamino)-7-cyano-1,3-benzothiazol-6-yl]oxy}phenyl)-2-(3-bromophenyl)-2-methylpropanamideYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-bromophenyl)-2-methylpropionic acid (89 mg, 0.361 mmol) in tetrahydrofuran (1 mL) were added oxalyl chloride (40 μL, 0.466 mmol) and N,N-dimethylformamide (10 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (1 mL). N-[6-(3-Aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]acetamide (100 mg, 0.308 mmol) produced in Example 12(ii) was added to the solution, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (12 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (6 mL) and saturated brine (6 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethanol to give the title compound (136 mg, 81%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (1 mL)
  3. stirringthe mixture was stirred at room temperature for 1 hr
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (6 mL) and saturated brine (6 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationInsoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20)
  9. concentrationthe obtained solution was concentrated under reduced pressure
  10. customThe residue was crystallized from ethanol

Sources & evidence

ORD record
ord-b9ee7bf11151476685f5ab33b804b796
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Linked notes

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