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

HRID 1774181Notes

Reaction equation

HRID 1774181 reaction equation
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]

Participants

6

Reactant 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)-

Product 1

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

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-3bf47e80da8f40beb3072258bc5980c1
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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