Sodium hydride → 3-(2-Fluorophenyl)-6-(2-Methyl-2H-1,2,4-Triazol-3-Ylmethoxy)-7-(3-Oxocyclobutyl)-1,2,4-Triazolo[4,3-b]Pyridazine

HRID 1369449Notes

Reaction equation

HRID 1369449 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:14]2[NH:15][C:16](=[O:24])[C:17]([CH:19]3[CH2:22][C:21](=[O:23])[CH2:20]3)=[CH:18][C:13]2=[N:12][N:11]=1.Cl.Cl[CH2:27][C:28]1[N:32]([CH3:33])[N:31]=[CH:30][N:29]=1>CN(C)C=O>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:14]2[N:15]=[C:16]([O:24][CH2:27][C:28]3[N:32]([CH3:33])[N:31]=[CH:30][N:29]=3)[C:17]([CH:19]3[CH2:20][C:21](=[O:23])[CH2:22]3)=[CH:18][C:13]2=[N:12][N:11]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 222853325-(chloromethyl)-1-methyl-1H-1,2,4-triazole hydrochlorideHCID 226099543-(2-Fluorophenyl)-7-(3-oxocyclobutyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one

Product 1

HCID 226099203-(2-Fluorophenyl)-6-(2-Methyl-2H-1,2,4-Triazol-3-Ylmethoxy)-7-(3-Oxocyclobutyl)-1,2,4-Triazolo[4,3-b]Pyridazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydride (60% dispersion in oil, 62 mg, 1.54 mmol) was added to a stirred solution of 3-(2-fluorophenyl)-7-(3-oxocyclobutyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one (0.23 g, 0.7 mmol) in anhydrous N,N-dimethylformamide (5 ml), and heated to 80° C. under an atmosphere of nitrogen for 0.5 hours. The solution was allowed to cool before addition of 5-chloromethyl-1-methyl-1H-1,2,4-triazole monohydrochloride (prepared using the conditions described in EP-A-170073) (0.14 g, 0.85 mmol). The reaction was then heated to 80° C., under an atmosphere of nitrogen, for 18 hours. The solution was allowed to cool, concentrated and the residue was purified by chromatography on silica using 0-5% methanol/dichloromethane as eluent to give the required product as a white solid. Data for the title compound: 1H NMR (360 MHz, CDCl3) δ3.29-3.38 (2H, m), 3.45-3.56 (2H, m), 3.73-3.82 (4H, m), 5.52 (2H, s), 7.26-7.31 (1H, m), 7.35-7.39 (1H, m), 7.56-7.60 (1H, m), 7.81-7.85 (1H, m), 7.88 (1H, s), 7.98 (1H, s); MS (ES+) m/e 394 [MH]+.

Workup

  1. customprepared
  2. temperatureThe reaction was then heated to 80° C., under an atmosphere of nitrogen, for 18 hours
  3. temperatureto cool
  4. concentrationconcentrated
  5. customthe residue was purified by chromatography on silica using 0-5% methanol/dichloromethane as eluent

Sources & evidence

ORD record
ord-ba2f38165e9c47e69836a939c1ecdae9
Source dataset
uspto-grants-2003_06
Patent number
US06579875B1

Reaction notes

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