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

HRID 1800463Notes

Reaction equation

HRID 1800463 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]([C:37]#[N:38])([CH3:36])[CH3:35])[CH:29]=3)[CH:25]=1)[N:13]=2>N1C=CC=CC=1>[C:37]([C:34]([C:30]1[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=1)[C:27]([NH:26][C:24]1[CH:25]=[C:20]([CH:21]=[CH:22][C:23]=1[CH3:40])[O:19][C:14]1[N:13]=[C:12]2[S:11][C:10]([NH:9][C:6]([C:4]3[N:3]=[CH:2][O:1][CH:5]=3)=[O:7])=[N:18][C:17]2=[CH:16][CH:15]=1)=[O:39])([CH3:36])[CH3:35])#[N:38]

Participants

4

Reactant 2

HCID 142814311,3-Oxazole-4-carbonyl chlorideHCID 86646000N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59507036N-[5-(3-{[3-(1-cyano-1-methylethyl)benzoyl]amino}-4-methylphenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]-1,3-oxazole-4-carboxamideYield 45%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1,3-Oxazole-4-carbonyl chloride synthesized above was suspended in pyridine (4.0 mL) at 0° C., N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.451 mmol) produced in Example C33(iv) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. 5% Aqueous sodium hydrogen carbonate solution (20 mL), ethyl acetate (20 mL) and hexane (20 mL) were added to the residue, and the yielded pale-yellow precipitate was collected by filtration. The obtained precipitate was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (108 mg, 45%) as a colorless powder.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. addition5% Aqueous sodium hydrogen carbonate solution (20 mL), ethyl acetate (20 mL) and hexane (20 mL) were added to the residue
  4. filtrationthe yielded pale-yellow precipitate was collected by filtration
  5. customThe obtained precipitate was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-77d93a85714f4c16889abb1a33eacc54
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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