Sodium hydride → {1-[2-(6-Methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1422715Notes

Reaction equation

HRID 1422715 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[N:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9]([OH:15])=[CH:8]2.[C:16]([O:20][C:21]([NH:23][CH:24]1[CH2:29][CH2:28][N:27]([CH2:30][CH2:31]OS(C)(=O)=O)[CH2:26][CH2:25]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C)C=O>[C:16]([O:20][C:21](=[O:22])[NH:23][CH:24]1[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][O:15][C:9]2[CH:10]=[N:11][C:12]3[C:7]([CH:8]=2)=[N:6][C:5]([O:4][CH3:3])=[CH:14][CH:13]=3)[CH2:26][CH2:25]1)([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonateHCID 1363794146-Methoxy-[1,5]naphthyridin-3-ol

Product 1

HCID 66747260{1-[2-(6-Methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl esterYield 30.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (55% purity, 9 mg, 0.22 mmol, 1.5 eq) is added at room temperature to a stirred solution of 6-methoxy-[1,5]naphthyridin-3-ol (42 mg, 0.22 mmol, 1.0 eq) in N,N-dimethylformamide (5 mL), followed by methanesulfonic acid 2-(4-tert-butoxycarbonylamino-piperidin-1-yl)-ethyl ester (102 mg, 0.22 mmol, 1.0 eq). The reaction mixture is irradiated by microwaves at 110° C. for 10 minutes, then solvent is evaporated, and the residue is extracted with ethyl acetate (3×10 mL) and water (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:1:0 to 0:9:1, v/v/v) to afford {1-[2-(6-methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as an orange solid (27 mg, 29% yield).

Workup

  1. customThe reaction mixture is irradiated by microwaves at 110° C. for 10 minutes
  2. customsolvent is evaporated
  3. extractionthe residue is extracted with ethyl acetate (3×10 mL) and water (10 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. customis purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:1:0 to 0:9:1, v/v/v)

Sources & evidence

ORD record
ord-6c06838c37424fab84b5cb99dde5bfde
Source dataset
uspto-grants-2015_01
Patent number
US08927542B2

Reaction notes

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