1,2-Dichloroethane → 4-{4-[2-(5-Tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-ylcarbamoyl]-benzenesulfonyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1986655Notes

Reaction equation

HRID 1986655 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:8]([O:24][CH3:25])=[C:9]([NH:11][C:12]([C:14]2[S:18][C:17]3[C:19]([NH2:23])=[CH:20][CH:21]=[CH:22][C:16]=3[CH:15]=2)=[O:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([S:44]([C:47]2[CH:52]=[CH:51][C:50]([C:53](O)=[O:54])=[CH:49][CH:48]=2)(=[O:46])=[O:45])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([S:44]([C:47]2[CH:48]=[CH:49][C:50]([C:53](=[O:54])[NH:23][C:19]3[C:17]4[S:18][C:14]([C:12](=[O:13])[NH:11][C:9]5[CH:10]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=[C:7]([NH:26][S:27]([CH3:30])(=[O:28])=[O:29])[C:8]=5[O:24][CH3:25])=[CH:15][C:16]=4[CH:22]=[CH:21][CH:20]=3)=[CH:51][CH:52]=2)(=[O:46])=[O:45])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 103435957-Amino-benzo[b]thiophene-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amideHCID 151696524-((4-((Tert-butoxy)carbonyl)piperazin-1-yl)sulfonyl)benzoic acid

Product 1

HCID 104854824-{4-[2-(5-Tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-ylcarbamoyl]-benzenesulfonyl}-piperazine-1-carboxylic acid tert-butyl esterYield 14.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

7-Amino-benzo[b]thiophene-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide (0.100 g, 0.223 mmol), 4-(4-carboxy-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester (0.160 g, 0.432 mmol), HOBT (0.060 g, 0.444 mmol) and EDC (0.080 g, 0.417 mmol) were dissolved in DMF (7.0 mL) and stirred at room temperature under an Ar atmosphere for 42 h. The reaction mixture was transferred to a separatory funnel containing water and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water, NH4Cl, brine and dried over MgSO4. The solvent was filtered and evaporated on a rotary evaporator. The resultant crude product was purified by chromatography (60% EtOAc/hexane) to give the desired 4-{4-[2-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-ylcarbamoyl]-benzenesulfonyl}-piperazine-1-carboxylic acid tert-butyl ester (25.5 mg).

Workup

  1. customThe reaction mixture was transferred to a separatory funnel
  2. extractionthe aqueous layer was extracted with EtOAc (3×10 mL)
  3. washThe combined organic extracts were washed with water, NH4Cl, brine
  4. dry with materialdried over MgSO4
  5. filtrationThe solvent was filtered
  6. customevaporated on a rotary evaporator
  7. customThe resultant crude product was purified by chromatography (60% EtOAc/hexane)

Sources & evidence

ORD record
ord-4e36273ac5ac4a31b80cfa925e019fda
Source dataset
uspto-grants-2009_06
Patent number
US07550461B2

Reaction notes

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