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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 587891
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HRID 587891 반응식
[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
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참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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%)

후처리

  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

출처 및 근거

ORD 기록
ord-921abccbdf6f4832a10e2b3ad2c20b57
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09227930B2

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