[F:1][C:2]1([F:17])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([OH:15])=[CH:14][C:9]=2[S:8][C:7]1=[O:16].C(=O)([O-])[O-].[Cs+].[Cs+].F[C:25]1[N:32]=[CH:31][CH:30]=[CH:29][C:26]=1[C:27]#[N:28]>CN1C(=O)CCC1.CO>[F:17][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][C:25]3[C:26]([C:27]#[N:28])=[CH:29][CH:30]=[CH:31][N:32]=3)=[CH:14][C:9]=2[S:8][C:7]1=[O:16]To a solution of 3-[(2,2-difluorocyclopropyl)methyl]-6-hydroxy-1,3-benzothiazol-2(3H)-one (18-2) (0.033 g, 0.13 mmol) in anhydrous NMP (1 mL) was added cesium carbonate (0.084 g, 0.26 mmol) and 2-fluoronicotinonitrile (0.024 g, 0.19 mmol). The reaction mixture was then heated under microwave irradiation at 100° C. for 10 minutes. The crude reaction mixture was then allowed to cool to room temperature, diluted with methanol and NMP, then filtered and concentrated. Purification of crude reaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water) gave 2-[(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)oxy]pyridine-3-carbonitrile (18-3) as an off-white solid. HRMS (M+H)+: observed=360.0623, calculated=360.0613.
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