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Methyl iodide → N-(2-(3-benzyl-6-fluoro-2-(3-hydroxy-3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-N,1-dimethyl-1H-imidazole-4-sulfonamide

HRID 82896
ノート
印刷プレビュー

反応式

HRID 82896 の反応式
[H-].[Na+].[CH2:3]([C@H:10]1[C:18]2[C:13](=[CH:14][C:15]([F:32])=[C:16]([O:19][CH2:20][CH2:21][NH:22][S:23]([C:26]3[N:27]=[CH:28][N:29]([CH3:31])[CH:30]=3)(=[O:25])=[O:24])[CH:17]=2)[CH2:12][C@H:11]1[N:33]1[CH2:36][C:35]([OH:38])([CH3:37])[CH2:34]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CI.[Cl-].[NH4+].[C:43](OCC)(=O)C>O1CCCC1>[CH2:3]([CH:10]1[C:18]2[C:13](=[CH:14][C:15]([F:32])=[C:16]([O:19][CH2:20][CH2:21][N:22]([CH3:43])[S:23]([C:26]3[N:27]=[CH:28][N:29]([CH3:31])[CH:30]=3)(=[O:25])=[O:24])[CH:17]=2)[CH2:12][CH:11]1[N:33]1[CH2:34][C:35]([OH:38])([CH3:37])[CH2:36]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66740580cis-N-(2-(3-benzyl-6-fluoro-2-(3-hydroxy-3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamideHCID 86583716Ammonium chloride ethyl acetate

生成物 1

HCID 56837062N-(2-(3-benzyl-6-fluoro-2-(3-hydroxy-3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-N,1-dimethyl-1H-imidazole-4-sulfonamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

At 0° C. sodium hydride (0.589 mg, 0.022 mmol) was added to a solution of cis-N-(2-(3-benzyl-6-fluoro-2-(3-hydroxy-3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (9.1 mg, 0.018 mmol; see example 206) in dry tetrahydrofuran (1 ml). The obtained suspension was stirred for 30 min at 0° C. and 1 h at room temperature. After dropwise addition of methyl iodide (1.216 μl. 0.019 mmol) the reaction mixture was stirred for 5 h and poured on a mixture of sat. ammonium chloride/ethyl acetate. The organic layer was separated and the aqueous layer washed twice with ethyl acetate. The combined organic layers were washed with sat. ammonium chloride, water and brine, dried over magnesium sulfate, filtered and evaporated to obtain the crude product as a pale yellow oil, that was purified on 1.5×5 cm SiO2-column using 5% methanol in dichloromethane to afford N-(2-(3-benzyl-6-fluoro-2-(3-hydroxy-3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-N,1-dimethyl-1H-imidazole-4-sulfonamide as clear oil. m=3.1 mg (33%)

後処理

  1. stirringwas stirred for 5 h
  2. customThe organic layer was separated
  3. washthe aqueous layer washed twice with ethyl acetate
  4. washThe combined organic layers were washed with sat. ammonium chloride, water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto obtain the crude product as a pale yellow oil, that
  9. customwas purified on 1.5×5 cm SiO2-column

出典と根拠

ORDレコード
ord-36fe4eeceb1a4e11ac60a449d73ca651
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08846743B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート