Bromine → N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide

HRID 2190370ノート

反応式

HRID 2190370 の反応式
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:33]=[CH:32][C:9]([O:10][C:11]2[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4([C:28]#[N:29])[CH2:27][CH2:26]4)[CH:20]=3)[CH:16]=2)=[CH:8][CH:7]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:7]2[CH:8]=[C:9]([O:10][C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]5([C:28]#[N:29])[CH2:26][CH2:27]5)[CH:20]=4)[CH:16]=3)[CH:32]=[CH:33][C:6]=2[N:5]=1

参加物

5

反応物 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 67312290N-[5-(4-aminophenoxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide

生成物 1

HCID 86655351N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide収率 79.1%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒3 回

実験手順

Potassium thiocyanate (7.00 g, 72 mmol) was suspended in acetic acid (120 mL) and the mixture was stirred at room temperature for 10 min. To the obtained solution was added a solution of N-[5-(4-aminophenoxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide (6.90 g, 18 mmol) in acetic acid (120 mL), and the mixture was further stirred at room temperature for 30 min. To the obtained solution was added dropwise slowly a solution of bromine (3.60 g, 22.5 mmol) in acetic acid (80 mL) and, after the completion of the dropwise addition, the mixture was further stirred at room temperature for 12 hr. The resulting yellow insoluble material was filtered off and washed with acetic acid. The filtrate and the washing were combined and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (400 mL), washed with 5% aqueous sodium hydrogencarbonate solution (200 mL×2) and saturated brine (200 mL), successively, 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=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (6.27 g, 79%) as a pale-yellow amorphous substance.

後処理

  1. stirringthe mixture was further stirred at room temperature for 30 min
  2. additionafter the completion of the dropwise addition
  3. stirringthe mixture was further stirred at room temperature for 12 hr
  4. filtrationThe resulting yellow insoluble material was filtered off
  5. washwashed with acetic acid
  6. concentrationconcentrated under reduced pressure
  7. washwashed with 5% aqueous sodium hydrogencarbonate solution (200 mL×2) and saturated brine (200 mL)
  8. dry with materialsuccessively, and dried over anhydrous sodium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  12. concentrationthe obtained solution was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-bcd6f397c0304dc799dd41924db9fcc1
出典データセット
uspto-grants-2012_12
特許番号
US08324395B2

反応ノート

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