Potassium Carbonate → 2-(4-(isoxazol-5-yl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2224286Notes

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.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:31][N:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[O:31]1[C:27]([C:24]2[CH:25]=[CH:26][C:21]([CH2:20][N:16]3[C:15](=[O:18])[N:4]4[N:5]=[CH:6][C:7]([C:8]5[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=5)=[C:2]([Cl:1])[C:3]4=[N:17]3)=[CH:22][CH:23]=2)=[CH:28][CH:29]=[N:30]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirring suspension of 8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one prepared as described in example 354G, and 5-(4-(bromomethyl)phenyl)isoxazole (122 mg, 0.51 mmol), prepared as described as in Example 250A in DMF (5 mL) at RT under argon was added K2CO3 (119 mg, 0.86 mmol). The resulting mixture was heated at 50° C. for 3 h. HPLC/MS analysis indicated complete reaction. The reaction mixture was concentrated under vacuum with co-evaporation of toluene (10 mL×2) to obtain a dark yellow solid. The crude product was purified by silica gel column chromatography (ISCO) eluting with hexanes/EtOAc to obtain pure title compound, 2-(4-(isoxazol-5-yl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (149 mg, 79%) as a yellow solid. MS [M+H]+ 438; HPLC retention time=3.55 min.

Workup

customprepared
customprepared
customreaction
concentrationThe reaction mixture was concentrated under vacuum with co-evaporation of toluene (10 mL×2)
customto obtain a dark yellow solid
customThe crude product was purified by silica gel column chromatography (ISCO)
washeluting with hexanes/EtOAc

Sources & evidence

ORD record: ord-bb0e9b66ad3c44db834089c01896a735
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07378418B2

Reaction notes

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