[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:11][C:12]1[CH:17]=[C:16](F)[C:15]([C:19]2[S:23][C:22]([NH2:24])=[N:21][N:20]=2)=[C:14]([F:25])[CH:13]=1>C1COCC1>[CH2:3]([O:10][C:16]1[CH:17]=[C:12]([Br:11])[CH:13]=[C:14]([F:25])[C:15]=1[C:19]1[S:23][C:22]([NH2:24])=[N:21][N:20]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1A stirred suspension of NaH (60% dispersion in mineral oil, 151 mg, 3.77 mmol) in THF (10 mL) was cooled under nitrogen in an ice bath. To this suspension was added a solution of benzyl alcohol (0.372 mL, 3.59 mmol) in THF (5 mL) drop-wise. On completion of addition, the resulting suspension was stirred at ice bath temperature for 5 minutes, then room temperature for 10 minutes, before being slowly added to a stirred, ice-bath cooled suspension of 5-(4-bromo-2,6-difluorophenyl)-1,3,4-thiadiazol-2-amine (1 g, 3.42 mmol) in THF (20 mL). The resulting yellow/brown suspension was stirred at ice bath temperature for 15 minutes, room temperature for 1 hour then heated at 50° C. for 18 hours. The reaction was quenched by addition of saturated NH4Cl(aq) (30 mL), diluted with water (30 mL), and extracted with EtOAc (100 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated onto silica gel and the crude material was purified by flash chromatography using an 80 g silica cartridge running an EtOAc/heptane gradient to afford the title compound as a pale yellow solid (488 mg, 37% yield). LC-MS: Rt 1.19 min; MS m/z 282.0 M+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 7.27-7.47 (m, 9H), 5.28 (s, 2H).
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