Dimethylformamide → N-[3-(2-chlorophenyl)-1-(piperidin-1-ylcarbonyl)propyl]-1H-indole-4-sulfonamide

HRID 537403Notes

Reaction equation

HRID 537403 reaction equation
C(OC([NH:8][CH:9]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])[C:10]([O:12]C)=O)=O)(C)(C)C.C[N:24]([CH:26]=O)[CH3:25].CCN(C(C)C)[CH:31]([CH3:33])[CH3:32].[NH:37]1[C:45]2[CH:44]=[CH:43][CH:42]=[C:41]([S:46](Cl)(=[O:48])=[O:47])[C:40]=2[CH:39]=[CH:38]1>C(Cl)Cl.C(O)(C(F)(F)F)=O.O>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][CH2:14][CH:9]([NH:8][S:46]([C:41]1[C:40]2[CH:39]=[CH:38][NH:37][C:45]=2[CH:44]=[CH:43][CH:42]=1)(=[O:48])=[O:47])[C:10]([N:24]1[CH2:26][CH2:33][CH2:31][CH2:32][CH2:25]1)=[O:12]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 552807991H-indole-4-sulfonyl chlorideHCID 66997238Methyl 2-[(tert-butoxycarbonyl)amino]-4-(2-chlorophenyl)butanoate

Product 1

HCID 58504856N-[3-(2-chlorophenyl)-1-(piperidin-1-ylcarbonyl)propyl]-1H-indole-4-sulfonamideYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of 1.1 g (3.4 mmol) of methyl 2-[(tert-butoxycarbonyl)amino]-4-(2-chlorophenyl)butanoate in 8 mL of 1:1 CH2Cl2/TFA is stirred for 1 h. The mixture is concentrated and 10 mL of DMF, 1.5 mL (8.5 mmol) of iPr2NEt, and 0.81 g (3.7 mmol) of indole-4-sulfonyl chloride are added. The mixture is stirred for 12 h, diluted with water, and extracted with EtOAc. The extract is washed with brine, dried over MgSO4, filtered and concentrated. The residue is purified by flash chromatography (0-100% EtOAc in hexanes) to provide 1.0 g (73%) of the sulfonamide. This material (0.48 g, 1.2 mmol) is then dissolved in 5 mL of dioxane and 2.9 mL (2.9 mmol) of 1 M NaOH. After starting material is consumed, the mixture is concentrated, redissolved in water, and extracted with CH2Cl2. The extract is discarded, and the pH of the aqueous solution is adjusted to 3 with 1 N HCl. The mixture is extracted with CH2Cl2/DMF. The extract is concentrated to provide 0.39 g (86%) of the acid 4-(2-chlorophenyl)-2-[(1H-indol-4-ylsulfonyl)amino]butanoic acid.

Workup

  1. concentrationThe mixture is concentrated
  2. extractionextracted with EtOAc
  3. washThe extract is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by flash chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f38c5ba68bf84b6688a7fb729ae9d2af
Source dataset
uspto-grants-2014_10
Patent number
US08859814B2

Reaction notes

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