Oxalyl chloride → N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}-4-methylphenoxy)-1,3-benzothiazol-2-yl]-1,3-oxazole-4-carboxamide

HRID 2190372Notes

Reaction equation

HRID 2190372 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[CH:18]=[C:17]([O:19][C:20]3[CH:21]=[CH:22][C:23]([CH3:40])=[C:24]([NH:26][C:27](=[O:39])[C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:34]5([C:37]#[N:38])[CH2:36][CH2:35]5)[CH:29]=4)[CH:25]=3)[CH:16]=[CH:15][C:13]=2[N:14]=1.O1C=C(C(O)=O)N=C1.C(Cl)(=O)C(Cl)=O>CN(C)C(=O)C.CN(C)C=O.O1CCCC1>[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:17]2[CH:16]=[CH:15][C:13]3[N:14]=[C:10]([NH:9][C:6]([C:4]4[N:3]=[CH:2][O:1][CH:5]=4)=[O:7])[S:11][C:12]=3[CH:18]=2)=[O:39])[CH2:36][CH2:35]1)#[N:38]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 142814301,3-Oxazole-4-carboxylic acidHCID 142814311,3-Oxazole-4-carbonyl chloride2×HCID 86655351N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 86655353N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}-4-methylphenoxy)-1,3-benzothiazol-2-yl]-1,3-oxazole-4-carboxamideYield 75%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of 1,3-oxazole-4-carbonyl chloride synthesized above in N,N-dimethylacetamide (3 mL) was added N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide (300 mg, 0.681 mmol) produced in Example A3(iv), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of 1,3-oxazole-4-carbonyl chloride synthesized in the same manner as in the above from 1,3-oxazole-4-carboxylic acid (30 mg, 0.265 mmol), oxalyl chloride (27 μL, 0.316 mmol), N,N-dimethylformamide (1 drop) and tetrahydrofuran (1 mL) in N,N-dimethylacetamide (1 mL), and the mixture was further stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, diluted with 5% aqueous sodium hydrogencarbonate solution (200 mL), and extracted with ethyl acetate (300 mL). The organic layer was washed with saturated brine (100 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 purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and triturated with ethyl acetate/hexane to give the title compound (3.84 g, 75%) as a colorless solid.

Workup

  1. stirringthe mixture was further stirred at room temperature for 3 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with 5% aqueous sodium hydrogencarbonate solution (200 mL)
  4. extractionextracted with ethyl acetate (300 mL)
  5. washThe organic layer was washed with saturated brine (100 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 purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  10. customtriturated with ethyl acetate/hexane

Sources & evidence

ORD record
ord-08d779ee4d8f4960b64bea244eb7b9f3
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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