3,4-Bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine → HCID 178424565, compound

HRID 927182

Reaction equation

HRID 927182 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])=[C:43]([CH3:51])[CH:42]=2)=[CH:29][C:30]=1[O:31]CC1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[OH:31][C:30]1[C:25](=[O:24])[NH:26][N:27]=[C:28]([CH2:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:49])([F:48])[F:50])=[C:43]([CH3:51])[CH:42]=2)[CH:29]=1

Participants

4

Reactant 2

HCID 712698973,4-Bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine2×HCID 1785188083-Hydroxy-6-(2-Phenylethyl)pyridazin-4(1h)-One

Product 1

HCID 178424565HCID 178424565, compoundYield 4%

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-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine (Intermediate 74) except THF was used as the solvent. The reaction mixture was filtered through a diatomacious earth cartridge, eluting with further THF and methanol. The filtrate was concentrated under reduced pressure and purified by reverse phase column chromatography (eluting with 5-100% aqueous acetonitrile with acid modifier). The desired fractions were combined and freeze dried to give a pale yellow solid, which was recrystallised from methyl tert-butyl ether to give a white solid. The filtrate was concentrated under reduced pressure, and the filtrate and crystals purified separately by preparative HPLC. The two batches were combined and recrystallised from a mixture of methyl tert-butyl ether and ethyl acetate to afford 4-hydroxy-6-(3-methyl-4-(trifluoromethyl)-phenethyl)pyridazin-3(2H)-one as a white solid (31 mg, 4%).

Workup

  1. customPrepared
  2. filtrationThe reaction mixture was filtered through a diatomacious earth cartridge
  3. washeluting with further THF and methanol
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by reverse phase column chromatography (eluting with 5-100% aqueous acetonitrile with acid modifier)
  6. customfreeze dried
  7. customto give a pale yellow solid, which
  8. customwas recrystallised from methyl tert-butyl ether
  9. customto give a white solid
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe filtrate and crystals purified separately by preparative HPLC
  12. customrecrystallised from a mixture of methyl tert-butyl ether and ethyl acetate

Sources & evidence

ORD record
ord-a50cd1838c034bcbbc2aee5863e460f0
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Linked notes

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