Methanol → 4-(2,5-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxazole

HRID 1929996Notes

Reaction equation

[CH:1]([C:4]1[N:8]2[N:9]=[C:10]([CH:13]=[O:14])[CH:11]=[CH:12][C:7]2=[N:6][N:5]=1)([CH3:3])[CH3:2].[F:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[CH:23]([N+:34]#[C-:35])S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].CO>O1CCOCC1.O>[F:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[C:23]1[N:34]=[CH:35][O:14][C:13]=1[C:10]1[CH:11]=[CH:12][C:7]2[N:8]([C:4]([CH:1]([CH3:3])[CH3:2])=[N:5][N:6]=2)[N:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine-6-carbaldehyde (0.150 g, 0.789 mmol, Preparation #2) in 1,4-dioxane (3 mL) was added 1,4-difluoro-2-(isocyano(tosyl)methyl)benzene (0.202 g, 0.657 mmol, Preparation #4), K2CO3 (0.218 g, 1.58 mmol) and MeOH (3.00 mL). The reaction mixture was heated to about 80° C. for about 3 h. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL). The organic layer was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography using heptane/EtOAc (gradient; 1:1 to 0:1) to give the title compound (0.161 g, 71% yield). LC/MS (Table 1, Method a) Rt=2.20 min; MS m/z: 342.1 (M+H)+.

Workup

extractionextracted with DCM (50 mL)
dry with materialThe organic layer was dried with MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record: ord-eca2dc0467944336a96f81b616d61fed
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188083B2

Reaction notes

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