Br[C:2]1[S:3][C:4]([C:7]2[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[CH:9][C:8]=2[F:15])=[N:5][N:6]=1.[CH3:16][NH:17][CH:18]1[CH2:23][C:22]([CH3:25])([CH3:24])[NH:21][C:20]([CH3:27])([CH3:26])[CH2:19]1>CN1C(=O)CCC1.C([O-])(O)=O.[Na+].O>[F:15][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([O:13][CH3:14])[C:7]=1[C:4]1[S:3][C:2]([N:17]([CH3:16])[CH:18]2[CH2:19][C:20]([CH3:26])([CH3:27])[NH:21][C:22]([CH3:25])([CH3:24])[CH2:23]2)=[N:6][N:5]=1A stirred solution of 2-bromo-5-(2-fluoro-6-methoxyphenyl)-1,3,4-thiadiazole (335 mg, 1.159 mmol) and N,2,2,6,6-pentamethylpiperidin-4-amine (197 mg, 1.159 mmol) in NMP (2.5 mL) was heated at 120° C. for ˜18 hours. The reaction mixture was diluted with saturated NaHCO3(aq) (30 mL), water (20 mL), and extracted with DCM (75 mL). The organic phase was separated, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to afford the crude product as a brown oil/liquid. The crude material was purified by UV directed preparative HPLC under acidic conditions (0.1% TFA), collecting at 298 nm. The product containing fractions were combined and loaded onto a 5 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (30 mL) then flushed with 7M NH3 in MeOH (20 mL). The MeOH/NH3 was removed in vacuo to afford the title compound as an orange oil (121 mg, 28% yield). LC-MS: Rt 0.88 min; MS m/z 379.4 [M+H]+; [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.49 (td, J=8.34, 6.57 Hz, 1H), 7.03 (d, J=8.59 Hz, 1H), 6.97 (t, J=9.09 Hz, 1H), 4.26-4.36 (m, 1H), 3.86 (s, 3H), 2.98 (s, 3H), 1.62 (dd, J=11.62, 2.53 Hz, 2H), 1.42 (t, J=12.13 Hz, 2H), 1.27 (br. s., 1H), 1.20 (s, 6H), 1.09 (s, 6H).
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