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

HRID 1972624ノート

反応式

HRID 1972624 の反応式
[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]

参加物

7

反応物 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chloride2 回HCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-45dceea75e604024b62baa039957f6fe
出典データセット
uspto-grants-2013_04
特許番号
US08431563B2

反応ノート

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