1,3-Oxazole-4-carbonyl chloride → N-[5-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}-4-methylphenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]-1,3-oxazole-4-carboxamide

HRID 1800454Notes

Reaction equation

HRID 1800454 reaction equation
[O:1]1[CH:5]=[C:4]([C:6](Cl)=[O:7])[N:3]=[CH:2]1.[NH2:9][C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([O:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:40])=[C:24]([NH:26][C:27](=[O:39])[C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]4([C:37]#[N:38])[CH2:36][CH2:35]4)[CH:29]=3)[CH:25]=1)[N:13]=2>N1C=CC=CC=1>[C:37]([C:34]1([C:30]2[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=2)[C:27]([NH:26][C:24]2[CH:25]=[C:20]([CH:21]=[CH:22][C:23]=2[CH3:40])[O:19][C:14]2[N:13]=[C:12]3[S:11][C:10]([NH:9][C:6]([C:4]4[N:3]=[CH:2][O:1][CH:5]=4)=[O:7])=[N:18][C:17]3=[CH:16][CH:15]=2)=[O:39])[CH2:36][CH2:35]1)#[N:38]

Participants

4

Reactant 2

HCID 142814311,3-Oxazole-4-carbonyl chlorideHCID 86645998N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl)-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 59507008N-[5-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}-4-methylphenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]-1,3-oxazole-4-carboxamideYield 77%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1,3-Oxazole-4-carbonyl chloride synthesized above was suspended in pyridine (2.0 mL) at 0° C., N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl)-3-(1-cyanocyclopropyl)benzamide (200 mg, 0.452 mmol) produced in Example C29(iv) was added, and the mixture was stirred at room temperature for 8 hr. The reaction mixture was concentrated under reduced pressure, 1% aqueous citric acid solution (50 mL) was added, and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate/hexane to give the title compound (125 mg, 77%) as a colorless powder.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure, 1% aqueous citric acid solution (50 mL)
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate (100 mL)
  5. washThe organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-fc82de2b55b544e99872491df1ceeb76
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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