Oxalyl chloride → 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

HRID 1025459Notes

Reaction equation

HRID 1025459 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18](O)=[O:19])(=[O:14])=[O:13])=[CH:7][CH:6]=1)=[O:4].C(Cl)(=O)C(Cl)=O.[NH2:30][C:31]1[S:32][C:33]2[CH2:60][CH2:59][CH2:58][CH2:57][C:34]=2[C:35]=1[C:36]([NH:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][CH2:46][C:47]2[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=2)=[CH:41][CH:40]=1)=[O:37]>CN(C=O)C.ClCCl.N1C=CC=CC=1>[CH3:54][O:53][C:51]([C:50]1[CH:49]=[CH:48][C:47]([CH2:46][CH2:45][C:42]2[CH:41]=[CH:40][C:39]([NH:38][C:36]([C:35]3[C:34]4[CH2:57][CH2:58][CH2:59][CH2:60][C:33]=4[S:32][C:31]=3[NH:30][C:18]([C:17]3[CH:16]=[C:15]([S:12]([NH:11][C:8]4[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=4)(=[O:14])=[O:13])[CH:23]=[CH:22][CH:21]=3)=[O:19])=[O:37])=[CH:44][CH:43]=2)=[CH:56][CH:55]=1)=[O:52]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 250374323-{[4-(Methoxycarbonyl)phenyl]sulfamoyl}benzoic acidHCID 68207883Methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate

Product 1

HCID 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)benzoateYield 97.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 347 mg of 3-{[4-(methoxycarbonyl)phenyl]sulfamoyl}benzoic acid, 0.090 mL of oxalyl chloride, 3.0 mL of dichloromethane, and one drop of DMF was stirred at room temperature for 2 hours, and then the reaction mixture was concentrated under reduced pressure. A mixture of the obtained crude product and 3.0 mL of dichloromethane was added to a mixture of 0.071 mL of pyridine, 300 mg of methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, and 2.5 mL of dichloromethane, followed by stirring at room temperature overnight. The reaction mixture was purified by silica gel column chromatography (hexane-chloroform) to obtain 505 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 as a yellow foamed solid. ESI+: 752

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additionA mixture of the
  3. customobtained crude product and 3.0 mL of dichloromethane
  4. stirringby stirring at room temperature overnight
  5. customThe reaction mixture was purified by silica gel column chromatography (hexane-chloroform)

Sources & evidence

ORD record
ord-1ff33536f46e4a95986f4bccbeea842a
Source dataset
uspto-grants-2014_05
Patent number
US08729068B2

Reaction notes

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