Dimethylformamide → HCID 59454496, compound

HRID 1097493Notes

Reaction equation

HRID 1097493 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:49]=[CH:50][C:51]=1[F:52])[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]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:27][C:28]1[CH:29]=[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:49]=[CH:50][C:51]=1[F:52])=[O:6]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 668102752-Chloro-3-(1-cyano-1-methylethyl)benzoic acidHCID 71819026HCID 71819026, compound

Product 1

HCID 59454496HCID 59454496, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-3-(1-cyano-1-methylethyl)benzoic acid (108 mg, 0.482 mmol) in tetrahydrofuran (1.5 mL) were added oxalyl chloride (52 μL, 0.601 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 (1.5 mL). N-[6-(3-Amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (150 mg, 0.407 mmol) produced in Example 30(vi) was added to the solution, and the mixture was stirred at room temperature for 10 min. The reaction mixture was diluted with ethyl acetate (10 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 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=50/50→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 (116 mg, 50%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (1.5 mL)
  3. stirringthe mixture was stirred at room temperature for 10 min
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 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=50/50→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-c7a6999b671f46cd858b5df0372a036d
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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