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

Reaction equation

HRID 1184652 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-13aec5ad380546a894ea2d1be06e15f3
Source dataset
uspto-grants-2014_03
Patent number
US08669229B2

Linked notes

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