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

HRID 335054
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HRID 335054 반응식
[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]
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참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide
용매
HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-9a64624b91b94ed1a5764fa7ec9efe30
출처 데이터셋
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08883850B2

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