Citric Acid → Methyl 4-(isopropyl {[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}amino)benzoate

HRID 926071Notes

Reaction equation

HRID 926071 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]3[C:26]4[CH2:27][CH2:28][CH2:29][CH2:30][C:25]=4[S:24][C:23]=3[NH:31][C:32]([C:34]3[CH:35]=[C:36]([S:40]([NH:43][C:44]4[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=4)(=[O:42])=[O:41])[CH:37]=[CH:38][CH:39]=3)=[O:33])=[O:21])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)=[O:4].[CH:54](I)([CH3:56])[CH3:55].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH:54]([N:43]([S:40]([C:36]1[CH:37]=[CH:38][CH:39]=[C:34]([C:32](=[O:33])[NH:31][C:23]2[S:24][C:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=3[C:22]=2[C:20](=[O:21])[NH:19][C:16]2[CH:15]=[CH:14][C:13]([CH2:12][CH2:11][C:8]3[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)=[CH:18][CH:17]=2)[CH:35]=1)(=[O:41])=[O:42])[C:44]1[CH:45]=[CH:46][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:52][CH:53]=1)([CH3:56])[CH3:55]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6362Isopropyl iodide2×HCID 11430Potassium CarbonateHCID 71238552Methyl 4-({[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}amino)benzoate

Product 1

HCID 71238164Methyl 4-(isopropyl {[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}amino)benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 350 mg of methyl 4-({[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}amino)benzoate, 0.070 mL of isopropyl iodide, 193 mg of potassium carbonate, and 3.5 mL of DMF was stirred at 80° C. overnight. Further, 0.14 mL of isopropyl iodide was added thereto, followed by further stirring at 80° C. overnight. To the reaction mixture was added an aqueous citric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine in this order, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-chloroform) to obtain 264 mg of methyl 4-(isopropyl {[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)phenyl]sulfonyl}amino)benzoate as a pale yellow solid.

Workup

  1. stirringby further stirring at 80° C. overnight
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane-chloroform)

Sources & evidence

ORD record
ord-277a0b27ef7548f0befb8b6dfeef9a4f
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

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