Water → HCID 66740620, compound

HRID 587893Notes

Reaction equation

HRID 587893 reaction equation
[CH2:1]([CH:8]1[C:16]2[C:11](=[CH:12][C:13]([F:28])=[C:14]([CH2:17][NH:18][S:19]([C:22]3[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=3)(=[O:21])=[O:20])[CH:15]=2)[CH2:10][CH:9]1[NH:29][C:30](=O)OCC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[K+].O>O1CCCC1>[CH2:1]([C@H:8]1[C:16]2[C:11](=[CH:12][C:13]([F:28])=[C:14]([CH2:17][NH:18][S:19]([C:22]3[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=3)(=[O:21])=[O:20])[CH:15]=2)[CH2:10][C@H:9]1[NH:29][CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([C@@H:8]1[C:16]2[C:11](=[CH:12][C:13]([F:28])=[C:14]([CH2:17][NH:18][S:19]([C:22]3[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=3)(=[O:21])=[O:20])[CH:15]=2)[CH2:10][C@H:9]1[NH:29][CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 21226445Aluminium lithium hydrideHCID 56837064ethyl 1-benzyl-5-fluoro-6-((1-methyl-1H-imidazole-4-sulfonamido)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate

Product 2

HCID 66740620HCID 66740620, compoundYield 24%HCID 66740699trans-N-([3-benzyl-6-fluoro-2-(methylamino)-2,3-dihydro-1H-inden-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamideYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To ethyl 1-benzyl-5-fluoro-6-((1-methyl-1H-imidazole-4-sulfonamido)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate (37.5 mg, 0.077 mmol; see example 208) in tetrahydrofuran (1 ml) was added lithium aluminium hydride 1M in tetrahydrofuran (0.231 ml, 0.231 mmol) and the reaction mixture was refluxed for 2 h. Cooled down to room temperature. Added 0.5N potassium hydroxide (1 ml) and water (7 ml), filtered over Celite, washed with tetrahydrofuran and the Celite filter cake was poured into tetrahydrofuran, refluxed for 30 min, and filtered again over Celite. The combined organic layers were evaporated, re-dissolved in dichloromethane, washed with sodium bicarbonate and brine, dried over MgSO4, filtered and evaporated to obtain the crude product as a pale yellow oil that was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to obtained the desired products cis-N-{[3-benzyl-6-fluoro-2-(methylamino)-2,3-dihydro-1H-inden-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide (7.9 mg, 24%) and trans-N-{[3-benzyl-6-fluoro-2-(methylamino)-2,3-dihydro-1H-inden-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide (3.5 mg, 11%)

Workup

  1. temperaturethe reaction mixture was refluxed for 2 h
  2. filtrationfiltered over Celite
  3. washwashed with tetrahydrofuran
  4. filtrationthe Celite filter cake
  5. additionwas poured into tetrahydrofuran
  6. temperaturerefluxed for 30 min
  7. filtrationfiltered again over Celite
  8. customThe combined organic layers were evaporated
  9. dissolutionre-dissolved in dichloromethane
  10. washwashed with sodium bicarbonate and brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated
  14. customto obtain the crude product as a pale yellow oil that
  15. customwas purified by flash silica gel chromatography on 4 g SiO2-cartridge

Sources & evidence

ORD record
ord-ce38e050ee054b67946a667c982e29a6
Source dataset
uspto-grants-2016_01
Patent number
US09227930B2

Reaction notes

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