Hydroxylamine HCl → 6-[6-Methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carboxamidoxime

HRID 2409981Notes

Reaction equation

HRID 2409981 reaction equation
[Cl-].[OH:2][NH3+:3].C(=O)([O-])O.[Na+].[CH3:9][O:10][C:11]1[CH:19]=[C:18]2[C:14]([C:15]([CH2:24][C:25]3[N:30]=[C:29]([C:31]#[N:32])[CH:28]=[CH:27][CH:26]=3)=[C:16]([C:20]3([CH3:23])[CH2:22][CH2:21]3)[NH:17]2)=[CH:13][CH:12]=1>CS(C)=O.O>[CH3:9][O:10][C:11]1[CH:19]=[C:18]2[C:14]([C:15]([CH2:24][C:25]3[N:30]=[C:29]([C:31](=[N:3][OH:2])[NH2:32])[CH:28]=[CH:27][CH:26]=3)=[C:16]([C:20]3([CH3:23])[CH2:22][CH2:21]3)[NH:17]2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 867032956-[6-methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carbonitrile

Product 1

HCID 1363443746-[6-Methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carboxamidoximeYield 106.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of hydroxylammonium chloride (117 mg) in dimethylsulfoxide (1.7 mL) was added sodium hydrogen carbonate (170 mg), and the mixture was stirred at 50° C. for 1 hour. Then, a solution of 6-[6-methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carbonitrile (53.6 mg) in dimethylsulfoxide (1.7 mL) was added dropwise thereto, followed by stirring at 80° C. for 2.5 hours. The reaction mixture was left to be cooled and diluted with water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain the title compound (62.9 mg). 1H-NMR (CDCl3) δ ppm: 0.68-0.76 (2H, m), 0.84-0.92 (2H, m), 1.34 (3H, s), 3.82 (3H, s), 4.35 (2H, s), 5.68 (2H, br s), 6.69 (1H, dd, J=2.3, 8.8 Hz), 6.82 (1H, d, J=2.3 Hz), 6.98-7.05 (1H, m), 7.23 (1H, d, J=8.8 Hz), 7.50 (1H, t, J=7.8 Hz), 7.66-7.73 (1H, m), 7.82 (1H, br s). ESI-MS (m/z): 351 (M+H)+

Workup

  1. stirringby stirring at 80° C. for 2.5 hours
  2. waitThe reaction mixture was left
  3. temperatureto be cooled
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e23db925a81a4ae0aeb5f1dff2a74197
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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