Sodium Hydroxide → 7-(3-Benzyloxy-cyclobutyl)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one

HRID 2306607Notes

Reaction equation

HRID 2306607 reaction equation
[OH-:1].[Na+].[CH2:3]([O:10][CH:11]1[CH2:14][CH:13]([C:15]2[C:20](Cl)=[N:19][N:18]3[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])=[N:23][N:24]=[C:17]3[CH:16]=2)[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>O1CCOCC1.O>[CH2:3]([O:10][CH:11]1[CH2:14][CH:13]([C:15]2[C:20](=[O:1])[NH:19][N:18]3[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])=[N:23][N:24]=[C:17]3[CH:16]=2)[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 226099487-(3-Benzyloxycyclobutyl)-6-chloro-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 226099297-(3-Benzyloxy-cyclobutyl)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4N Sodium hydroxide (3 ml, 12 mmol) was added to a solution of 7-(3-benzyloxycyclobutyl)-6-chloro-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (0.98 g, 2.4 mmol) in 1,4-dioxane (30 ml) and water (8 ml), heated to reflux for 18 hours. The solvent was evaporated and the residue dissolved in diethyl ether (50 ml) and water (50 ml) and separated. The aqueous layer was acidified to pH 2 with 2N hydrochloric acid and the resultant solid collected by filtration, washed with water (50 ml), followed by diethyl ether (50 ml) and dried under vacuum at 100° C. for 18 hours. Data for the title compound: 1H NMR (400 MHz, CDCl3), cis and trans isomers present in 4:1 ratio, δ 1.95-2.03 (1.6H, m), 2.31-2.38 (0.4H, m), 2.50-2.56 (0.4H, m), 2.68-2.76 (1.6, m), 3.05-3.13 (1H, m), 3.65-3.73 (0.2H, m), 4.06-4.15 (0.8H, m), 4.46 (2H, s), 6.80-6.87 (2H, m), 7.22-7.37 (6H, m), 7.55-7.61 (1H, m), 7.63 (0.8H, m), 7.68 (0.2H, s); MS (ES+) m/e 391 [MH]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 hours
  3. customThe solvent was evaporated
  4. dissolutionthe residue dissolved in diethyl ether (50 ml)
  5. customwater (50 ml) and separated
  6. filtrationthe resultant solid collected by filtration
  7. washwashed with water (50 ml)
  8. customdried under vacuum at 100° C. for 18 hours

Sources & evidence

ORD record
ord-0f8c675369f4430796b7f6215978e3ff
Source dataset
uspto-grants-2004_12
Patent number
US06828322B2

Reaction notes

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