Cl.[F:2][CH:3]1[CH2:8][CH2:7][CH2:6][NH:5][CH2:4]1.[C:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](F)=[CH:13][CH:12]=1)#[N:10].C1CCN2C(=NCCC2)CC1>[OH-].[Na+]>[F:2][CH:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11]([C:9]#[N:10])=[CH:12][CH:13]=2)[CH2:4]13-Fluoropiperidine hydrochloride (106 mg, 0.76 mol) was dissolved in sodium hydroxide (1 M, 10 mL) and extracted with dichloromethane (4×10 mL), the combined extracts were dried over sodium sulfate, filtered and evaporated. Pyridine (2 mL) was added, followed by 1-cyano-4-fluoronaphthalene (108 mg, 0.63 mmol) and the vial was shaken at 110° C. overnight. GC-MS and TLC showed only very little conversion. DBU (10 μL) was added and the shaking was continued for 2 weeks at 110° C., after which GC-MS showed ˜50% conversion. The reaction was worked up in the same way as 165RL60 and purified by silica gel column chromatography eluted with a stepwise gradient of 0-60% ethyl acetate in n-heptane to give the title compound (29.3 mg, 12%) as a solid.
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