3,4-bis(Benzyloxy)-6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]-ethynyl}pyridazine → HCID 178518819, compound

HRID 927178Notes

Reaction equation

HRID 927178 reaction equation
OC1C(=O)NN=C(CCC2C=CC=CC=2)C=1.C([O:24][C:25]1[N:26]=[N:27][C:28]([C:39]#[C:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][C:42]=2[F:51])=[CH:29][C:30]=1[O:31]CC1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[F:51][C:42]1[CH:43]=[C:44]([C:47]([F:49])([F:50])[F:48])[CH:45]=[CH:46][C:41]=1[CH2:40][CH2:39][C:28]1[CH:29]=[C:30]([OH:31])[C:25](=[O:24])[NH:26][N:27]=1

Participants

4

Reactant 2

HCID 712705113,4-bis(Benzyloxy)-6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]-ethynyl}pyridazine2×HCID 1785188083-Hydroxy-6-(2-Phenylethyl)pyridazin-4(1h)-One

Product 1

HCID 178518819HCID 178518819, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared as described for 4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]-ethynyl}pyridazine (Intermediate 70) except that THF was used as the solvent. The reaction was filtered through diatomaceous earth flushing with further tetrahydrofuran and concentrated in vacuo. The residue was purified by column chromatography (silica C18 cartridge; eluting with 0-65% acetonitrile in water with acid modifier). The appropriate fractions were combined and concentrated in vacuo to remove the acetonitrile before the aqueous portion was extracted with ethyl acetate (×2), dried (MgSO4) and concentrated in vacuo. The resulting solid was recrystallised from a mixture of methyl tert-butyl ether and heptane to afford 6-{2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-4-hydroxy-2,3-dihydropyridazin-3-one as a cream solid (29% yield).

Workup

  1. customPrepared
  2. filtrationThe reaction was filtered through diatomaceous earth
  3. customflushing with further tetrahydrofuran
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica C18 cartridge; eluting with 0-65% acetonitrile in water with acid modifier)
  6. concentrationconcentrated in vacuo
  7. customto remove the acetonitrile before the aqueous portion
  8. extractionwas extracted with ethyl acetate (×2)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe resulting solid was recrystallised from a mixture of methyl tert-butyl ether and heptane

Sources & evidence

ORD record
ord-48576914959d4acbba65ccfe8bb5ea6f
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Reaction notes

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