Acetonitrile → cis-N-(2-{[2-(azetidin-1-yl)-3-benzyl-6-fluoro-2,3-dihydro-1H-inden-5-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide

HRID 82889Notes

Reaction equation

HRID 82889 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][CH2:34][CH2:35]Br.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.ClCCl>[N:1]1([C@H:2]2[C@@H:10]([CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:9]3[C:4](=[CH:5][C:6]([F:31])=[C:7]([O:18][CH2:19][CH2:20][NH:21][S:22]([C:25]4[N:26]=[CH:27][N:28]([CH3:30])[CH:29]=4)(=[O:24])=[O:23])[CH:8]=3)[CH2:3]2)[CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 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 66741188cis-N-(2-{[2-(azetidin-1-yl)-3-benzyl-6-fluoro-2,3-dihydro-1H-inden-5-yl]oxy}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 (17.9 mg, 0.040 mmol) was added 1,3-dibromopropane (4.90 μL, 0.048 mmol) and potassium carbonate (6.12 mg, 0.044 mmol) in water (1 mL)+1 drop acetonitrile were added. Microwave at 120° C. for 20 min. Evaporated acetonitrile, re-dissolved in dichloromethane and extracted with water and brine, dried over sodium bi-carbonate, filtered and evaporated to obtain the crude product, that was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to afford cis-N-(2-{[2-(azetidin-1-yl)-3-benzyl-6-fluoro-2,3-dihydro-1H-inden-5-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide as a clear glass. m=4.0 mg (20%)

Workup

  1. additionwere added
  2. extractionextracted with water and brine
  3. dry with materialdried over sodium bi-carbonate
  4. filtrationfiltered
  5. customevaporated
  6. customto obtain the crude product, that
  7. customwas purified by flash silica gel chromatography on 4 g SiO2-cartridge

Sources & evidence

ORD record
ord-f8fdc25fa0384d688387930dfee248e0
Source dataset
uspto-grants-2014_09
Patent number
US08846743B2

Reaction notes

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