Dimethylformamide → HCID 86655398, compound

HRID 2190460Notes

Reaction equation

HRID 2190460 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:45]=[CH:46][CH:47]=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[CH:33]=1>O1CCCC1.C(OCC)(=O)C.O>[C:40]([NH:39][C:37]1[S:38][C:34]2[CH:33]=[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]5([C:14]#[N:15])[CH2:13][CH2:12]5)[C:2]=4[Cl:1])[CH:47]=[CH:46][CH:45]=3)[CH:44]=[CH:43][C:35]=2[N:36]=1)(=[O:42])[CH3:41]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 668103062-Chloro-3-(1-cyanocyclopropyl)benzoic acidHCID 86655397N-[6-(3-aminophenoxy)-1,3-benzothiazol-2-yl]acetamide

Product 1

HCID 86655398HCID 86655398, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-3-(1-cyanocyclopropyl)benzoic acid (237 mg, 1.07 mmol) in tetrahydrofuran (4 mL) were added oxalyl chloride (170 mg, 1.34 mmol) and N,N-dimethylformamide (10 μL), and the mixture was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in N,N-dimethylacetamide (4 mL). N-[6-(3-Aminophenoxy)-1,3-benzothiazol-2-yl]acetamide (160 mg, 0.534 mmol) was added and the mixture was stirred at room temperature for 2 hr. To the reaction mixture were added water (100 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with saturated brine (10 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→0/100), and triturated with ethyl acetate/diisopropyl ether to give the title compound (215 mg, 80%) as a yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in N,N-dimethylacetamide (4 mL)
  3. stirringthe mixture was stirred at room temperature for 2 hr
  4. customThe organic layer was separated
  5. washwashed with saturated brine (10 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→0/100)
  10. customtriturated with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-d185c5f14886453f8fa245b05e81a6bf
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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