Dimethylformamide → 2-chloro-3-(1-cyanocyclopropyl)-N-[3-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide

HRID 1097457Notes

Reaction equation

HRID 1097457 reaction equation
[Cl:1][C:2]1[C:10]([C:11]2([C:14]#[N:15])[CH2:13][CH2:12]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:27][C:28]1[CH:29]=[C:30]([CH:49]=[CH:50][CH:51]=1)[O:31][C:32]1[CH:46]=[CH:45][C:35]2[N:36]=[C:37]([NH:39][C:40]([CH:42]3[CH2:44][CH2:43]3)=[O:41])[S:38][C:34]=2[C:33]=1[C:47]#[N:48]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]([C:11]2([C:14]#[N:15])[CH2:13][CH2:12]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:27][C:28]1[CH:51]=[CH:50][CH:49]=[C:30]([O:31][C:32]2[CH:46]=[CH:45][C:35]3[N:36]=[C:37]([NH:39][C:40]([CH:42]4[CH2:44][CH2:43]4)=[O:41])[S:38][C:34]=3[C:33]=2[C:47]#[N:48])[CH:29]=1)=[O:6]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 668103062-Chloro-3-(1-cyanocyclopropyl)benzoic acidHCID 86644685N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 594544692-chloro-3-(1-cyanocyclopropyl)-N-[3-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamideYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-3-(1-cyanocyclopropyl)benzoic acid (75 mg, 0.339 mmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (36 μL, 0.420 mmol) and N,N-dimethylformamide (20 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 (2 mL). N-[6-(3-Aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (100 mg, 0.29 mmol) produced in Example 3(vi) was added to the solution, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (50 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 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 basic silica gel column chromatography (ethyl acetate/n-hexane=70/30→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give the title compound (113 mg, 72%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (2 mL)
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 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 basic silica gel column chromatography (ethyl acetate/n-hexane=70/30→100/0)
  9. concentrationthe obtained solution was concentrated under reduced pressure
  10. customThe residue was recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-2173be6ba90d404e83a191cc5319c217
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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