Oxalyl chloride → N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}-2-chlorophenyl)-2-chloro-3-(1-cyano-1-methylethyl)benzamide

HRID 1800630노트

반응식

HRID 1800630 반응식
[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:40]=[CH:41][C:42]=1[Cl:43])[O:26][C:27]1[N:32]=[C:31]2[S:33][C:34]([NH:36][C:37](=[O:39])[CH3:38])=[N:35][C:30]2=[CH:29][CH:28]=1>O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[C:37]([NH:36][C:34]1[S:33][C:31]2[C:30]([N:35]=1)=[CH:29][CH:28]=[C:27]([O:26][C:25]1[CH:40]=[CH:41][C:42]([Cl:43])=[C:23]([NH:22][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])[C:2]=3[Cl:1])[CH:24]=1)[N:32]=2)(=[O:39])[CH3:38]

참가 물질

7

반응물 3

HCID 65578Oxalyl chlorideHCID 668102752-Chloro-3-(1-cyano-1-methylethyl)benzoic acidHCID 86646053N-[5-(3-amino-4-chlorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]acetamide

생성물 1

HCID 59506991N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}-2-chlorophenyl)-2-chloro-3-(1-cyano-1-methylethyl)benzamide수율 56%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

2-Chloro-3-(1-cyano-1-methylethyl)benzoic acid (120 mg, 0.537 mmol) produced in Example C61(v) was dissolved in tetrahydrofuran (3.0 mL) and N,N-dimethylformamide (0.01 mL), oxalyl chloride (56.87 μL, 0.672 mmol) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, toluene (10 mL) was added to the residue, and the mixture was again concentrated under reduced pressure. The residue was dissolved in N,N-dimethylacetamide (3.0 mL), N-[5-(3-amino-4-chlorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]acetamide (90 mg, 0.269 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (80 mL), the organic layer was washed with aqueous sodium hydrogen carbonate solution (50 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0), further purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0→ethyl acetate/methanol=90/10), and crystallized from diethyl ether to give the title compound (81 mg, 56%) as white crystals.

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure, toluene (10 mL)
  2. additionwas added to the residue
  3. concentrationthe mixture was again concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in N,N-dimethylacetamide (3.0 mL)
  5. stirringthe mixture was stirred at room temperature for 2 hr
  6. washthe organic layer was washed with aqueous sodium hydrogen carbonate solution (50 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0)
  10. customfurther purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0→ethyl acetate/methanol=90/10)
  11. customcrystallized from diethyl ether

출처 및 근거

ORD 기록
ord-bc53a25399e34065a49a0ed5554ceb83
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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