Acetonitrile → N-(2-(3-benzyl-6-fluoro-2-(3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide

HRID 82891Notes

Reaction equation

HRID 82891 reaction equation
[NH2:1][CH:2]1[CH:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([F:31])=[C:7]([O:18][CH2:19][CH2:20][NH:21][S:22]([C:25]3[N:26]=[CH:27][N:28]([CH3:30])[CH:29]=3)(=[O:24])=[O:23])[CH:8]=2)[CH2:3]1.Br[CH2:33][CH:34]([CH3:37])[CH2:35]Cl.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.ClCCl>[CH2:11]([CH:10]1[C:9]2[C:4](=[CH:5][C:6]([F:31])=[C:7]([O:18][CH2:19][CH2:20][NH:21][S:22]([C:25]3[N:26]=[CH:27][N:28]([CH3:30])[CH:29]=3)(=[O:24])=[O:23])[CH:8]=2)[CH2:3][CH:2]1[N:1]1[CH2:35][CH:34]([CH3:37])[CH2:33]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 955661-Bromo-3-chloro-2-methylpropaneHCID 66740582N-(2-(2-amino-3-benzyl-6-fluoro-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide

Product 1

HCID 56837079N-(2-(3-benzyl-6-fluoro-2-(3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

To N-(2-(2-amino-3-benzyl-6-fluoro-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (20.7 mg, 0.047 mmol), 10 equivalents 1-bromo-3-chloro-2-methylpropane and potassium carbonate(70.8 mg) in water (1 mL) +1 drop acetonitrile were added. Microwave at 120° C. Evaporated acetonitrile, re-dissolved in dichloromethane and extracted with water and brine, dried over sodium bicarbonate, filtered and evaporated to obtain the crude product and was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to afford N-(2-(3-benzyl-6-fluoro-2-(3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide as a clear glass m=2.0 mg (8.6%)

Workup

  1. customat 120° C
  2. extractionextracted with water and brine
  3. dry with materialdried over sodium bicarbonate
  4. filtrationfiltered
  5. customevaporated
  6. customto obtain the crude product
  7. customwas purified by flash silica gel chromatography on 4 g SiO2-cartridge

Sources & evidence

ORD record
ord-81e1ba96982249148de3da2ca9baced6
Source dataset
uspto-grants-2014_09
Patent number
US08846743B2

Reaction notes

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