5-Iodo-2,3-dihydropyridazin-3-one → (S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one

HRID 1774181

反応式

HRID 1774181 の反応式
CC([O-])(C)C.[K+].[I:7][C:8]1[CH:13]=[N:12][NH:11][C:10](=[O:14])[CH:9]=1.CS(O[C@H:20]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([F:37])[CH:31]=1)[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])(=O)=O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Si:23]([O:22][CH2:21][C@@H:20]([N:11]1[C:10](=[O:14])[CH:9]=[C:8]([I:7])[CH:13]=[N:12]1)[C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([F:37])[CH:31]=1)([C:26]([CH3:28])([CH3:29])[CH3:27])([CH3:25])[CH3:24]

参加物

6

反応物 3

HCID 166383305-Iodo-2,3-dihydropyridazin-3-oneHCID 23665647Potassium tert-butoxideHCID 71726881Benzenemethanol, 4-chloro-alpha-((((1,1-dimethylethyl)dimethylsilyl)oxy)methyl)-3-fluoro-, 1-methanesulfonate, (alphaR)-

生成物 1

HCID 86696678(S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one収率 63%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

1.0M KOt-Bu (2.64 mL, 2.64 mmol) in THF and tetrabutylammonium iodide (0.0749 g, 0.203 mmol) were added to a solution of 5-iodopyridazin-3(2H)-one (0.45 g, 2.03 mmol) in THF (10 mL). The mixture was stirred at room temperature for 10 minutes before (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate (1.16 g, 3.04 mmol) was added as a solution in THF (10 mL) The reaction was heated to reflux for 90 hours, then cooled to room temperature and concentrated. The residue was taken up in ethyl acetate and washed with water (2×). The organics were dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (25:1) to give (S)-2-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-5-iodopyridazin-3(2H)-one (0.65 g, 63%). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=2.0 Hz, 1H), 7.45 (d, J=2.2 Hz, 1H), 7.35 (m, 1H), 7.23 (m, 1H), 7.16 (m, 1H), 6.09 (m, 1H), 4.34 (m, 1H), 4.01 (m, 1H), 0.81 (s, 9H), 0.01 (s, 3H), −0.01 (s, 3H).

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 90 hours
  3. concentrationconcentrated
  4. washwashed with water (2×)
  5. customThe organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified via column chromatography
  9. washeluting with hexanes/ethyl acetate (25:1)

出典と根拠

ORDレコード
ord-3bf47e80da8f40beb3072258bc5980c1
出典データセット
uspto-grants-2016_02
特許番号
US09259470B2

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