Pyridine → N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2-propanesulfonamide

HRID 1972624노트

반응식

HRID 1972624 반응식
[NH2:1][CH2:2][C@H:3]1[CH2:8][N:7]([S:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.N1C=CC=CC=1.[CH:36]([S:39](Cl)(=[O:41])=[O:40])([CH3:38])[CH3:37].CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[S:13]1[CH:14]=[CH:15][CH:16]=[C:12]1[S:9]([N:7]1[CH2:6][CH2:5][N:4]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:26])([F:27])[F:25])=[CH:21][CH:22]=2)[C@@H:3]([CH2:2][NH:1][S:39]([CH:36]([CH3:38])[CH3:37])(=[O:41])=[O:40])[CH2:8]1)(=[O:10])=[O:11]

참가 물질

7

반응물 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chloride2회HCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

생성물 1

HCID 56932936N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2-propanesulfonamide수율 7.5%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (108 mg, 0.240 mmol) in CH2Cl2 (3 mL) was added pyridine (50 μL, 0.618 mmol, Sigma-Aldrich, St. Louis, Mo.) followed by isopropylsulfonyl chloride (27.0 μL, 0.240 mmol, Sigma-Aldrich, St. Louis, Mo.). After stirring at room temperature for 12 h, Hünig's base (0.5 mL) and more isopropylsulfonyl chloride (27.0 μL, 0.240 mmol) were added. The mixture was then heated at 60° C. for 12 h. MeOH (2 mL) was added and the mixture was concentrated. The residue was partitioned between CH2Cl2 and saturated aqueous NH4Cl. The organic layer was concentrated and purified on silica gel (1 to 4% MeOH in CH2Cl2) then by preparative TLC (1 to 4% MeOH in CH2Cl2) to give N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2-propanesulfonamide (10 mg) as a mixture of two isomers.

후처리

  1. temperatureThe mixture was then heated at 60° C. for 12 h
  2. concentrationthe mixture was concentrated
  3. customThe residue was partitioned between CH2Cl2 and saturated aqueous NH4Cl
  4. concentrationThe organic layer was concentrated
  5. custompurified on silica gel (1 to 4% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-45dceea75e604024b62baa039957f6fe
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431563B2

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