Oxalyl chloride → Methyl 4-{2-[4-({[2-({3-[cyclopropyl(4-ethoxy-4-oxobutyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate

HRID 1025451Notes

Reaction equation

HRID 1025451 reaction equation
[CH:1]1([N:4]([CH2:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[S:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11](O)=[O:12])(=[O:7])=[O:6])[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:31][C:32]1[S:33][C:34]2[CH2:61][CH2:60][CH2:59][CH2:58][C:35]=2[C:36]=1[C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([CH2:46][CH2:47][C:48]2[CH:57]=[CH:56][C:51]([C:52]([O:54][CH3:55])=[O:53])=[CH:50][CH:49]=2)=[CH:42][CH:41]=1)=[O:38]>CN(C=O)C.ClCCl.N1C=CC=CC=1>[CH:1]1([N:4]([CH2:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[S:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([NH:31][C:32]2[S:33][C:34]3[CH2:61][CH2:60][CH2:59][CH2:58][C:35]=3[C:36]=2[C:37]([NH:39][C:40]2[CH:41]=[CH:42][C:43]([CH2:46][CH2:47][C:48]3[CH:49]=[CH:50][C:51]([C:52]([O:54][CH3:55])=[O:53])=[CH:56][CH:57]=3)=[CH:44][CH:45]=2)=[O:38])=[O:12])(=[O:7])=[O:6])[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 68207883Methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoateHCID 712386223-[Cyclopropyl(4-ethoxy-4-oxobutyl)sulfamoyl]benzoic acid

Product 1

HCID 71238521Methyl 4-{2-[4-({[2-({3-[cyclopropyl(4-ethoxy-4-oxobutyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoateYield 81.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3.00 g of 3-[cyclopropyl(4-ethoxy-4-oxobutyl)sulfamoyl]benzoic acid, 0.70 mL of oxalyl chloride, 33 mL of dichloromethane, and one drop of DMF was stirred at room temperature for 2 hours, and the reaction mixture was concentrated under reduced pressure. A mixture of the obtained crude product and 33 mL of dichloromethane was added to a mixture of 0.70 mL of pyridine, 3.33 g of methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, and 33 mL of dichloromethane, followed by stirring at room temperature for 2 hours. The reaction mixture was purified by silica gel column chromatography (hexane-chloroform) and column chromatography (ethyl acetate) using NH silica gel in this order. The obtained solid was washed with ethanol to obtain 4.82 g of methyl 4-{2-[4-({[2-({3-[cyclopropyl(4-ethoxy-4-oxobutyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate as a pale yellow solid.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additionA mixture of the
  3. customobtained crude product and 33 mL of dichloromethane
  4. stirringby stirring at room temperature for 2 hours
  5. customThe reaction mixture was purified by silica gel column chromatography (hexane-chloroform) and column chromatography (ethyl acetate)
  6. washThe obtained solid was washed with ethanol

Sources & evidence

ORD record
ord-54e9bd5915504eb18f1f46293c44ddb1
Source dataset
uspto-grants-2014_05
Patent number
US08729068B2

Reaction notes

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