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

HRID 537403노트

반응식

HRID 537403 반응식
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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 21863450Trifluoroacetic acid methylene chloride용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-f38c5ba68bf84b6688a7fb729ae9d2af
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859814B2

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