Hydrogen Peroxide → HCID 118114602, compound

HRID 1050521Notes

Reaction equation

HRID 1050521 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:10]2)=[CH:5][C:4]=1[NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:31])=[CH:26][CH:25]=1)#[N:2].[OH-:38].[Na+].OO>CO.CS(C)=O.C(#N)C.CCOC(C)=O>[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:10]2)=[CH:5][C:4]=1[NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([N:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)=[O:31])=[CH:26][CH:25]=1)(=[O:38])[NH2:2]

Participants

8

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 118114785HCID 118114785, compound

Product 1

HCID 118114602HCID 118114602, compoundYield 90%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-tert-butyl 1-(6-cyano-5-(4-(morpholine-4-carbonyl)phenylamino)pyridin-3-yl)piperidin-3-ylcarbamate (96) in MeOH (15 mL) and DMSO (1.5 mL) was added solid NaOH (100 mg) and 30% H2O2 (1.5 mL). The mixture was stirred at RT for 20 min, diluted with acetonitrile (5 mL), and EtOAc (200 mL) 10 min later. The organic phase was washed with water ×2, dried, and concentrated in vacuo. The residue was subjected to flash column chromatography with 0 to 5% MeOH in DCM to give (R)-tert-butyl 1-(6-carbamoyl-5-(4-(morpholine-4-carbonyl)phenylamino)pyridin-3-yl)piperidin-3-ylcarbamate (97) (yield >90%). (R)-tert-butyl 1-(6-carbamoyl-5-(4-(morpholine-4-carbonyl)phenylamino)pyridin-3-yl)piperidin-3-ylcarbamate (97) was treated with 4N HCl in dioxane (30 mL) for 30 min. The mixture was concentrated in vacuo to dryness to afford (R)-5-(3-aminopiperidin-1-yl)-3-(4-(morpholine-4-carbonyl)phenylamino)picolinamide, HCl salt (98).

Workup

  1. washThe organic phase was washed with water ×2
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96d6504729cc49d9b047a662a9da92fc
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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