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 587891Notes

Reaction equation

HRID 587891 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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%)

Workup

  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

Sources & evidence

ORD record
ord-921abccbdf6f4832a10e2b3ad2c20b57
Source dataset
uspto-grants-2016_01
Patent number
US09227930B2

Reaction notes

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