Water → N-(3-{3-[3-(5-Fluoro-3-methyl-1H-indol-2-yl)propyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 428889Notes

Reaction equation

HRID 428889 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH:19]3[CH:17]([C:18]3([C:22]3[CH:23]=[C:24]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:25]=[CH:26][CH:27]=3)[CH3:21])[CH2:16]1)=O)=[C:5]2[CH3:33].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][CH2:12][CH2:13][N:15]1[CH2:20][CH:19]3[CH:17]([C:18]3([C:22]3[CH:23]=[C:24]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:25]=[CH:26][CH:27]=3)[CH3:21])[CH2:16]1)=[C:5]2[CH3:33]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 21226445Aluminium lithium hydrideHCID 22141190N-(3-{3-[3-(5-fluoro-3-methyl-1H-indol-2-yl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

Product 1

HCID 22141356N-(3-{3-[3-(5-Fluoro-3-methyl-1H-indol-2-yl)propyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 97.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-{3-[3-(5-fluoro-3-methyl-1H-indol-2-yl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide (Preparation 128, 100 mg, 0.213 mmol) in anhydrous tetrahydrofuran (2.5 ml) under a nitrogen atmosphere at 0° C. was added dropwise lithium aluminium hydride (1.0M solution in tetrahydrofuran, 0.42 ml, 0.42 mmol) and the reaction mixture was stirred at room temperature overnight. The rapidly stirred reaction mixture was treated sequentially with water (0.45 ml), sodium hydrogen carbonate (450 mg) and ethyl acetate (10 ml). After 5 min, the reaction mixture was filtered and concentrated in vacuo to afford 95 mg of a colourless oil. This was purified by chromatography using a Biotage Flash 12™ cartridge packed with silica gel (8 g) eluting with hexane:ethyl acetate (100:0 to 0:100 over 30 min) then ethyl acetate methanol (100:0 to 0:100 over 15 min) to afford the title compound as a white foam (56 mg, 46%).

Workup

  1. customThe rapidly stirred reaction mixture
  2. waitAfter 5 min
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3ccd0cca904f441da7a80c00511f3ef9
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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