Water → HCID 22141315, compound

HRID 428879Notes

Reaction equation

HRID 428879 reaction equation
[CH3:1][C:2]1([C:21]2[CH:22]=[C:23]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:24]=[CH:25][CH:26]=2)[CH:7]2[CH:3]1[CH2:4][N:5]([C:8](=O)[CH2:9][C:10]1[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH3:19])[CH:11]=1)[CH2:6]2.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]1([C:21]2[CH:22]=[C:23]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])[CH:24]=[CH:25][CH:26]=2)[CH:7]2[CH:3]1[CH2:4][N:5]([CH2:8][CH2:9][C:10]1[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH3:19])[CH:11]=1)[CH2:6]2

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 21226445Aluminium lithium hydrideHCID 22141196N-(3-{6-methyl-3-[2-(1-methyl-1H-indol-3-yl)acetyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

Product 1

HCID 22141315HCID 22141315, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-{6-methyl-3-[2-(1-methyl-1H-indol-3-yl)acetyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide (Preparation 117, 55 mg, 0.126 mmol) in anhydrous tetrahydrofuran (1 ml) under a nitrogen atmosphere at 0° C. was added dropwise lithium aluminium hydride (1.0M solution in tetrahydrofiran, 0.26 ml, 0.26 mmol) and the reaction mixture was stirred at room temperature for 3 h. The rapidly stirred reaction mixture was treated sequentially with water (0.26 ml), sodium hydrogen carbonate (250 mg) and ethyl acetate (10 ml). After 30 min, the reaction mixture was filtered and concentrated in vacuo to afford a colourless oil. This was purified by preparative HPLC (condition 8) to give a pale yellow oil which was partitioned between dichioromethane (10 ml) and aqueous potassium carbonate solution (4% w:v, 5 ml). The layers were separated and the organic layer was washed with water (3 ml), dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a colourless oil (28 mg, 52%).

Workup

  1. customThe rapidly stirred reaction mixture
  2. waitAfter 30 min
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated in vacuo
  5. customto afford a colourless oil
  6. customThis was purified by preparative HPLC (condition 8)
  7. customto give a pale yellow oil which
  8. customwas partitioned between dichioromethane (10 ml) and aqueous potassium carbonate solution (4% w:v, 5 ml)
  9. customThe layers were separated
  10. washthe organic layer was washed with water (3 ml)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f294312d105b484780dd08f88a9c2908
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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