Potassium Carbonate → 4-(Trifluoromethyl)benzyl-8-chloro-7-(4-chlorophenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one

HRID 2224274Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[N:4]([C:15](=[O:18])[NH:16][N:17]=2)[N:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[C:19]([O-])([O-])=O.[K+].[K+].[F:25][C:26]([F:36])([F:35])[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1CBr>CN(C=O)C.CCOC(C)=O>[F:36][C:26]([F:25])([F:35])[C:27]1[CH:28]=[CH:31][C:32]([CH2:19][N:16]2[C:15](=[O:18])[N:4]3[N:5]=[CH:6][C:7]([C:8]4[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=4)=[C:2]([Cl:1])[C:3]3=[N:17]2)=[CH:33][CH:34]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 8-chloro-7-(4-chlorophenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one (0.54 g, 1.91 mmol), prepared as described in Example 354, in DMF (5 mL) at RT was added K2CO3 (0.40 g, 2.87 mmol) and 2-(trifluoromethyl)benzyl bromide (0.595 g, 2.49 mmol). The reaction mixture was heated at 55° C. for 4 h. After this time, the mixture was diluted with EtOAc (150 mL). The resultant solution was washed with water and saturated aqueous NaCl. The organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using hexanes:EtOAc (2:1) to afford 0.74 g of the title compound, 2-(4-(trifluoromethyl)benzyl-8-chloro-7-(4-chloro-phenyl)-2H-[1,2,4]triazolo[4,3-b]pyridazin-3-one as a yellow solid. HPLC RT: 3.84 min; MS, M+H=439. 1H NMR (CDCl3): δ 8.08 (s, 1H), 7.44-7.61 (m, 8H), 5.30 (s, 2H).

Workup

washThe resultant solution was washed with water and saturated aqueous NaCl
dry with materialThe organic layer was dried (MgSO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record: ord-569f29a6bd6b4dd38c5c58c9a38ea25d
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07378418B2

Reaction notes

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