Methyl iodide → 2-(4-((3-(4-Methoxypiperidin-1-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline

HRID 454925Notes

Reaction equation

HRID 454925 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[C:19]([N:24]3[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26][CH2:25]3)=[N:20][CH:21]=[CH:22][N:23]=2)[CH2:13][CH2:12]1.[C:31]([O-])([O-])=O.[Cs+].[Cs+].IC>C(#N)C>[CH3:31][O:30][CH:27]1[CH2:28][CH2:29][N:24]([C:19]2[C:18]([O:17][CH:14]3[CH2:13][CH2:12][N:11]([C:2]4[CH:3]=[CH:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:1]=4)[CH2:16][CH2:15]3)=[N:23][CH:22]=[CH:21][N:20]=2)[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 585478291-(3-((1-(Quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidin-4-OL

Product 1

HCID 546712402-(4-((3-(4-Methoxypiperidin-1-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinolineYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(3-((1-(quinolin-2-yl)piperidin-4-yl)oxy)pyrazin-2-yl)piperidin-4-ol (see EXAMPLE 1.1; 100 mg, 0.25 mmol) in dry acetonitrile (CH3CN) (10 mL) was added Cs2CO3 (162 mg, 0.5 mmol). The reaction mixture was cooled to 0° C. with an ice bath, and iodomethane (70 mg, 0.50 mmol) was added dropwise to the reaction mixture. 1 hour later, the reaction mixture was warmed to RT, and stirred overnight. Then the reaction mixture was washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum to give the crude product. The crude product was purified via flash chromatography on silica gel (20% to 45% EtOAc in petroleum ether) to give 2-(4-((3-(4-methoxypiperidin-1-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline (81 mg, 0.19 mmol, 78% yield) as a white solid. ESI-MS (M+1): 420 calc. for C24H29N5O2 419.

Workup

  1. temperature1 hour later, the reaction mixture was warmed to RT
  2. washThen the reaction mixture was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto give the crude product
  7. customThe crude product was purified via flash chromatography on silica gel (20% to 45% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-59a5cdf9d1cf466a9a6785a4d9665974
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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