Dimethylformamide → HCID 59454487, compound

HRID 455173Notes

Reaction equation

HRID 455173 reaction equation
[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:8]([C:16]([OH:18])=O)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:30][C:31]1[CH:32]=[C:33]([CH:52]=[CH:53][CH:54]=1)[O:34][C:35]1[CH:49]=[CH:48][C:38]2[N:39]=[C:40]([NH:42][C:43]([CH:45]3[CH2:47][CH2:46]3)=[O:44])[S:41][C:37]=2[C:36]=1[C:50]#[N:51]>O1CCCC1.C(OCC)(=O)C>[C:1]([N:5]1[C:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[C:8]([C:16]([NH:30][C:31]2[CH:54]=[CH:53][CH:52]=[C:33]([O:34][C:35]3[CH:49]=[CH:48][C:38]4[N:39]=[C:40]([NH:42][C:43]([CH:45]5[CH2:47][CH2:46]5)=[O:44])[S:41][C:37]=4[C:36]=3[C:50]#[N:51])[CH:32]=2)=[O:18])[CH:7]=[N:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 8078174936129-68-9HCID 86644685N-[6-(3-aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 59454487HCID 59454487, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-tert-butyl-5-phenyl-1H-pyrazole-4-carboxylic acid (67 mg, 0.274 mmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (29 μL, 0.338 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 (80 mg, 0.228 mmol) produced in Example 3(vi) was added to the solution, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (25 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (15 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=40/60→100/0), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (73 mg, 55%) 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 12 hr
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (15 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=40/60→100/0)
  9. concentrationthe obtained solution was concentrated under reduced pressure
  10. customThe residue was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-382f037e8e4044bba3e9afe6b93679a2
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

Loading…