[N:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][N:12]=2)[N:9]=1)=[C:2]=[S:3].[OH:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]2([C:29]#N)[CH2:28][CH2:27][CH2:26]2)=[CH:20][CH:19]=1.C[OH:32].Cl>CC(N(C)C)=O>[OH:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:2](=[S:3])[N:1]([C:4]3[CH:5]=[CH:6][C:7]4[N:8]([C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][N:12]=4)[N:9]=3)[C:29](=[O:32])[C:25]32[CH2:28][CH2:27][CH2:26]3)=[CH:20][CH:19]=1A mixture of 6-isothiocyanato-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (Intermediate 8, 545 mg, 2.22 mmol) and 1-((4-hydroxyphenyl)amino)cyclobutanecarbonitrile (Intermediate 25, 418 mg, 2.22 mmol) in DMA (15 mL) was heated to 60° C. for 2 h. MeOH (10 mL) and HCl (2M, 10 mL) were added and the mixture was refluxed for 1 h. The mixture was cooled to room temperature and slowly poured into an ice/water bath. The dark brown solid was filtered, washed with water, dried, and purified by reverse phase HPLC (Acetonitrile/water:TFA) to afford 5-(4-hydroxyphenyl)-6-thioxo-7-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-5,7-diazaspiro[3.4]octan-8-one as a light brown solid. LCMS [M+1]+ 435.4.
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