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

반응식

HRID 1774181 반응식
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]

참가 물질

6

반응물 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)-

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 8028Tetrahydrofuran용매3회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-3bf47e80da8f40beb3072258bc5980c1
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09259470B2

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