Potassium bis(trimethylsilyl)amide → 1-[(1S)-1-(4-Chloro-3-fluorophenyl)-2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]-4-[2-(methylthio)-4-pyrimidinyl]-2(1H)-pyridinone

HRID 2365792ノート

反応式

HRID 2365792 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][S:12][C:13]1[N:18]=[C:17]([C:19]2[CH:24]=[CH:23][NH:22][C:21](=[O:25])[CH:20]=2)[CH:16]=[CH:15][N:14]=1.CS(O[C@H:31]([C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[C:43]([F:48])[CH:42]=1)[CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])(=O)=O>C1COCC1>[Si:34]([O:33][CH2:32][C@@H:31]([N:22]1[CH:23]=[CH:24][C:19]([C:17]2[CH:16]=[CH:15][N:14]=[C:13]([S:12][CH3:11])[N:18]=2)=[CH:20][C:21]1=[O:25])[C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[C:43]([F:48])[CH:42]=1)([C:37]([CH3:39])([CH3:40])[CH3:38])([CH3:36])[CH3:35]

参加物

5

反応物 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 71726881Benzenemethanol, 4-chloro-alpha-((((1,1-dimethylethyl)dimethylsilyl)oxy)methyl)-3-fluoro-, 1-methanesulfonate, (alphaR)-HCID 717270054-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one

生成物 1

HCID 866966481-[(1S)-1-(4-Chloro-3-fluorophenyl)-2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]-4-[2-(methylthio)-4-pyrimidinyl]-2(1H)-pyridinone収率 63%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

1.0M KHMDS (5.09 mL, 5.09 mmol) as a solution in THF was added to a cold (0° C.) suspension of 4-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one (0.93 g, 4.24 mmol) in THF (20 mL). The reaction mixture was stirred at 0° C. for 10 minutes before (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate (2.44 g, 6.36 mmol) was added as a solution in THF (5 mL). The reaction was heated to reflux for 30 hours and then cooled to room temperature and concentrated. The residue was taken up in ethyl acetate (200 mL) and washed with water. The organics were dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (4:1) to give (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one (1.35 g, 63%) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J=5.0 Hz, 1H), 7.43 (m, 2H), 7.34 (d, J=5.0 Hz, 1H), 7.32-7.28 (m, 2H), 7.16 (m, 1H), 6.85 (m, 1H), 6.24 (m, 1H), 4.35 (m, 1H), 4.23 (m, 1H), 2.65 (s, 3H), 0.88 (s, 9H), 0.03 (s, 3H), −0.03 (s, 3H); m/z (APCI-pos) M+1=506.1, 508.1.

後処理

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 30 hours
  3. concentrationconcentrated
  4. washwashed with water
  5. customThe organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified via column chromatography
  9. washeluting with hexanes/ethyl acetate (4:1)

出典と根拠

ORDレコード
ord-8d30d188bed647e2af2ace84a4265292
出典データセット
uspto-grants-2014_04
特許番号
US08697715B2

反応ノート

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