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

HRID 2190372노트

반응식

HRID 2190372 반응식
[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]

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 142814301,3-Oxazole-4-carboxylic acidHCID 142814311,3-Oxazole-4-carbonyl chloride2회HCID 86655351N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 8028Tetrahydrofuran용매HCID 31374Dimethylacetamide용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-08d779ee4d8f4960b64bea244eb7b9f3
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324395B2

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