CS(O[C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]2[S:13][C:14]3[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:15]=3[N:16]=2)[CH2:7]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(#N)C.[NH:31]1[CH2:34][CH2:33][CH2:32]1>C(OCC)C>[N:31]1([C@@H:6]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:7]2)[CH2:34][CH2:33][CH2:32]1One equivalent of (S)-1-(6-bromobenzo[d]thiazol-2-yl)piperidin-3-yl methanesulfonate (Reference Example 10, 0.078 g, 0.2 mmol) and two equivalents of potassium carbonate (55.3 mg, 0.40 mmol) were weighed into a 2.5 mL Biotage microwave vial equipped with a magnetic stirbar. Acetonitrile (1 mL) was added, then 6 equivalents of azetidine (68.5 mg, 1.2 mmol) was weighed into the reaction mixture. The vial was sealed with a septum cap and the reaction mixture was stirred at 80° C. for 72 hours. The reaction mixture was transferred to a 100 mL round bottom flask (methanol rinse). Volatiles were removed under reduced pressure and the residue was partitioned between ethyl acetate and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give an oil. The oil was purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF10-4g, 100% dichloromethane to 98:2 dichloromethane/2 M NH3 in methanol). Fractions containing product were combined and concentrated under reduced pressure to give an oil that was dissolved in diethyl ether and dried (MgSO4). The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give a semi-solid that was triturated with diethyl ether/hexane to give (R)-2-(3-(azetidin-1-yl)piperidin-1-yl)-6-bromobenzo[d]thiazole as a solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.23-1.38 (m, 1H), 1.53-1.69 (m, 1H), 1.80-1.96 (m, 2H), 2.11 (pentet, J=7 Hz, 2H), 2.32-2.43 (m, 1H), 2.93-3.02 (m, 1H), 3.22-3.38 (m, 5H), 3.79 (dt, J=4, 13 Hz, 1H), 3.96 (dd, J=4, 13 Hz, 1H), 7.33 (d, J=9 Hz, 1H), 7.39 (dd, J=2, 9 Hz, 1H), 7.79 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 352 (M+H)+.
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