Methyl iodide → N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide

HRID 335054Notes

Reaction equation

HRID 335054 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:17][CH:18]=2)=[CH:4][C:3]=1[C:24]([NH:26][C@H:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C@@H:28]1[OH:33])=[O:25].[C:34](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.C(OCC)(=O)C>[OH:33][C@H:28]1[CH2:29][CH2:30][CH2:31][CH2:32][C@@H:27]1[NH:26][C:24]([C:3]1[CH:4]=[C:5]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:17][CH:18]=2)[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]=1[O:1][CH3:34])=[O:25]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 547557181-Hydroxy-N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide

Product 1

HCID 71281209N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-hydroxy-N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide (Example 6, 0.120 g, 0.271 mmol) in 4 mL of DMF was added potassium carbonate (0.041 g, 0.30 mmol) and iodomethane (0.042 g, 0.30 mmol). After 24 hours, the reaction was diluted with ethyl acetate, washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-10% methanol in dichloromethane to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 457.4 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.50 (br s, 1H), 8.30 (br s, 1H), 8.22-8.11 (m, 2H), 8.03 (s, 1H), 7.92 (d, J=6.9 Hz, 1H), 7.84 (br s, 1H), 7.70 (br s, 1H), 7.57 (br s, 2H), 6.44 (br s, 1H), 4.44 (s, 2H), 4.03 (s, 3H), 3.98 (br s, 1H), 3.53 (br s, 1H), 2.36-2.14 (m, 3H), 1.79 (br s, 2H), 1.47-1.26 (m, 3H).

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography
  6. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-9a64624b91b94ed1a5764fa7ec9efe30
Source dataset
uspto-grants-2014_11
Patent number
US08883850B2

Reaction notes

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