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

HRID 82892Notes

Reaction equation

HRID 82892 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][CH:6]=[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[CH2:32][CH:33]([CH3:36])[CH2:34]Cl.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.ClCCl>[CH2:11]([CH:10]1[C:9]2[C:4](=[CH:5][CH:6]=[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[CH2:34][CH:33]([CH3:36])[CH2:32]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 56837046N-(2-(2-amino-3-benzyl-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide

Product 1

HCID 56837076N-(2-(3-benzyl-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-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (43 mg, 0.101 mmol; see example 193), 1-bromo-3-chloro-2-methylpropane (0.093 mL, 0.807 mmol) and potassium carbonate(111 mg, 0.807 mmol) in water (1 mL)+1 drop acetonitrile were added. Microwave at 120° C. for 40 min. Evaporated acetonitrile, re-dissolved in dichloromethane and extracted with water and brine, dried over sodium bicarbonate, filtered and evaporated to obtain the crude product as a brown oil, that was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to afford N-(2-(3-benzyl-2-(3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide as a yellow oil. m=4.9 mg (10%)

Workup

  1. extractionextracted with water and brine
  2. dry with materialdried over sodium bicarbonate
  3. filtrationfiltered
  4. customevaporated
  5. customto obtain the crude product as a brown oil, that
  6. customwas purified by flash silica gel chromatography on 4 g SiO2-cartridge

Sources & evidence

ORD record
ord-e852f03941b24fd8b2165149a4faf733
Source dataset
uspto-grants-2014_09
Patent number
US08846743B2

Reaction notes

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