Dimethyl Sulfoxide → 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine

HRID 1184652

反応式

HRID 1184652 の反応式
[CH3:1][S:2]([CH3:4])=O.C(OC(=O)C)(=O)C.[CH3:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=1[C:19]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([C:29]([N:31]2[C:37]3[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:36]=3[CH:35]([OH:43])[CH2:34][CH2:33][CH2:32]2)=[O:30])=[C:26]([CH3:28])[CH:27]=1)=[O:20].[OH-].[Na+]>O.C(O)(=O)C>[Cl:42][C:40]1[CH:39]=[CH:38][C:37]2[N:31]([C:29](=[O:30])[C:25]3[CH:24]=[CH:23][C:22]([NH:21][C:19](=[O:20])[C:18]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[CH3:12])=[CH:27][C:26]=3[CH3:28])[CH2:32][CH2:33][CH2:34][CH:35]([O:43][CH2:1][S:2][CH3:4])[C:36]=2[CH:41]=1

参加物

7

反応物 4

HCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 216237Tolvaptan

生成物 1

HCID 251342157-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 962Water溶媒

反応条件

温度
70 °C

実験手順

Dimethylsulfoxide (DMSO) (3 ml), acetic anhydride (1.5 ml), and acetic acid (1.5 ml) were added to tolvaptan (1.0 g, 2.2 mmol), and the mixture was stirred at 70° C. for 4 hours. Water and 1N aqueous sodium hydroxide solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=80:20→20:80). The purified product was concentrated under reduced pressure to obtain 0.62 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine as white amorphous solid.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washwashed with an aqueous saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration and concentration under reduced pressure
  5. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=80:20→20:80)
  6. concentrationThe purified product was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-13aec5ad380546a894ea2d1be06e15f3
出典データセット
uspto-grants-2014_03
特許番号
US08669229B2

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