Potassium Carbonate → 4-(4-Chloro-6-methylquinolin-2-yl)-8-phenoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

HRID 540151Notes

Reaction equation

HRID 540151 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][C:22]([OH:24])=[CH:23][C:17]=3[S:16](=[O:26])(=[O:25])[CH2:15][CH2:14]2)[CH:3]=1.I[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][C:22]([O:24][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:23][C:17]=3[S:16](=[O:26])(=[O:25])[CH2:15][CH2:14]2)[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 75605N,N-Dimethylglycine hydrochlorideHCID 712553274-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-ol 1,1-dioxide

Product 1

HCID 712551874-(4-Chloro-6-methylquinolin-2-yl)-8-phenoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxideYield 720.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-ol 1,1-dioxide (250.0 mg, 0.65 mmol, prepared in analogy to 4-(4-chloroquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-ol 1,1-dioxide in Example 34), iodo-benzene (0.1 mL, 0.089 mmol), copper(I) iodide (74.0 mg, 0.35 mmol), N,N-dimethylglycine hydrochloride (72.0 mg, 0.52 mmol) and potassium carbonate (267.0 mg, 1.9 mmol) in dimethyl sulfoxide (1.5 mL). The reaction mixture was heated with stirring at 120° C. for 6 hours. After being cooled to room temperature, the reaction mixture was extracted with ethyl acetate (150 mL×2), washed with water (50 mL×2) and a saturated aqueous ammonium chloride solution (50 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 298.0 mg of the crude product as a yellow oil which was used for next step without further purification. MS obsd. (ESI+) [(M+H)+] 465.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureAfter being cooled to room temperature
  3. extractionthe reaction mixture was extracted with ethyl acetate (150 mL×2)
  4. washwashed with water (50 mL×2)
  5. dry with materiala saturated aqueous ammonium chloride solution (50 mL×2), dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7c347e8d0ae0494ab9c556c3312fb974
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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