Bromine → N-(5-[(2-Amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1800522

반응식

HRID 1800522 반응식
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]2[C:14]([Cl:34])=[CH:15][C:16]([F:33])=[C:17]([NH:19][C:20](=[O:32])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=3)[CH:18]=2)=[N:10][CH:11]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:11]2[C:6]([N:5]=1)=[CH:7][CH:8]=[C:9]([O:12][C:13]1[C:14]([Cl:34])=[CH:15][C:16]([F:33])=[C:17]([NH:19][C:20](=[O:32])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=3)[CH:18]=1)[N:10]=2

참가 물질

5

반응물 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 68419277N-{5-[(5-aminopyridin-2-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide

생성물 1

HCID 86646015N-(5-[(2-Amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide수율 90.9%

시약·촉매·용매 1

HCID 176Acetic Acid용매3회

실험 절차

Potassium thiocyanate (1.50 g, 3.53 mmol) was suspended in acetic acid (15 mL), and the mixture was stirred at room temperature for 10 min. A solution of N-{5-[(5-aminopyridin-2-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide (1.42 g, 3.22 mmol) in acetic acid (15 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 10 min. A solution of bromine (591 mg, 3.70 mmol) in acetic acid (10 mL) was slowly added dropwise to the obtained solution. After the completion of the dropwise addition, the mixture was stirred at room temperature for 20 hr. The yielded yellow insoluble material was filtered off, and washed with acetic acid. The filtrate and the washing fluid were combined, and concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate (150 mL), and the solution was washed with saturated aqueous sodium hydrogen carbonate solution (150 mL) and saturated brine (150 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 basic silica gel column chromatography (hexane/ethyl acetate=70/30→20/80), and the obtained solution was concentrated under reduced pressure to give the title compound (1.41 g, 83%) as a yellow amorphous substance.

후처리

  1. stirringthe mixture was further stirred at room temperature for 10 min
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 20 hr
  4. filtrationThe yielded yellow insoluble material was filtered off
  5. washwashed with acetic acid
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe obtained residue was dissolved in ethyl acetate (150 mL)
  8. washthe solution was washed with saturated aqueous sodium hydrogen carbonate solution (150 mL) and saturated brine (150 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationThe insoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=70/30→20/80)
  13. concentrationthe obtained solution was concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-15f9b13a272f40dfb696c8d9d7b3dc53
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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