Thionyl Chloride → 3-(1-cyanocyclopropyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide

HRID 2190364Notes

Reaction equation

HRID 2190364 reaction equation
[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4]1)#[N:2].S(Cl)(Cl)=O.[NH2:19][C:20]1[CH:21]=[C:22]([CH:39]=[CH:40][CH:41]=1)[O:23][C:24]1[CH:38]=[CH:37][C:27]2[N:28]=[C:29]([NH:31][C:32]([CH:34]3[CH2:36][CH2:35]3)=[O:33])[S:30][C:26]=2[CH:25]=1>C1(C)C=CC=CC=1.N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([NH:19][C:20]2[CH:41]=[CH:40][CH:39]=[C:22]([O:23][C:24]3[CH:38]=[CH:37][C:27]4[N:28]=[C:29]([NH:31][C:32]([CH:34]5[CH2:35][CH2:36]5)=[O:33])[S:30][C:26]=4[CH:25]=3)[CH:21]=2)=[O:11])[CH2:4][CH2:5]1)#[N:2]

Participants

7

Reactant 3

HCID 24386Thionyl ChlorideHCID 574410393-(1-Cyanocyclopropyl)benzoic acidHCID 86655349N-[6-(3-aminophenoxy)-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 866553503-(1-cyanocyclopropyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamideYield 67.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 1140TolueneSolvent

Procedure

To a suspension of 3-(1-cyanocyclopropyl)benzoic acid (156.5 mg, 0.836 mmol) in toluene (5 mL) was added thionyl chloride (0.2 mL, 2.74 mmol) and the mixture was heated under reflux for 2 hr. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The obtained residue was used as 3-(1-cyanocyclopropyl)benzoyl chloride. 3-(1-Cyanocyclopropyl)benzoyl chloride prepared above was dissolved in pyridine (5 mL), N-[6-(3-aminophenoxy)-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (114.8 mg, 352.8 gmol) and N,N-dimethylpyridine-4-amine (23.9 mg, 195.6 μmol) were added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was concentrated under reduced pressure, diluted with dilute hydrochloric acid (50 ml), and extracted with ethyl acetate (100 mL). The organic layer was washed with saturated aqueous sodium hydrogencarbonate solution (50 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 (ethyl acetate/hexane=2/98→80/20) to give the title compound (117 mg, 67%) as a pale-brown amorphous substance.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hr
  3. concentrationconcentrated under reduced pressure
  4. custom3-(1-Cyanocyclopropyl)benzoyl chloride prepared
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additiondiluted with dilute hydrochloric acid (50 ml)
  7. extractionextracted with ethyl acetate (100 mL)
  8. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution (50 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/98→80/20)

Sources & evidence

ORD record
ord-5e415922d2ee4454ad87e36655f4bf1c
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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