Dimethylformamide → HCID 86644702, compound

HRID 455223Notes

Reaction equation

HRID 455223 reaction equation
[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[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:48]=[CH:49][CH:50]=1)[O:31][C:32]1[CH:44]=[CH:43][C:35]2[N:36]=[C:37]([NH:39][C:40](=[O:42])[CH3:41])[S:38][C:34]=2[C:33]=1[N+:45]([O-:47])=[O:46]>O1CCCC1.C(OCC)(=O)C>[C:40]([NH:39][C:37]1[S:38][C:34]2[C:33]([N+:45]([O-:47])=[O:46])=[C:32]([O:31][C:30]3[CH:29]=[C:28]([NH:27][C:4](=[O:6])[C:3]4[CH:7]=[CH:8][CH:9]=[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])[C:2]=4[Cl:1])[CH:50]=[CH:49][CH:48]=3)[CH:44]=[CH:43][C:35]=2[N:36]=1)(=[O:42])[CH3:41]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 668102752-Chloro-3-(1-cyano-1-methylethyl)benzoic acidHCID 86644703HCID 86644703, compound

Product 1

HCID 86644702HCID 86644702, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-3-(1-cyano-1-methylethyl)benzoic acid (360 mg, 1.60 mmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (172 μL, 2.00 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 (2.5 mL). N-[6-(3-Aminophenoxy)-7-nitro-1,3-benzothiazol-2-yl]acetamide (460 mg, 1.34 mmol) was added to the solution, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (50 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was successively purified by silica gel column chromatography (ethyl acetate/n-hexane=50/50→100/0), and 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 crystallized from 2-butanone/n-hexane to give the title compound (300 mg, 41%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (2.5 mL)
  3. stirringthe mixture was stirred at room temperature for 12 hr
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 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 successively purified by silica gel column chromatography (ethyl acetate/n-hexane=50/50→100/0), and 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 crystallized from 2-butanone/n-hexane

Sources & evidence

ORD record
ord-be00f52db973483dae366d1d0c783e3c
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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