[C:1]([C:3]1[CH:22]=[CH:21][C:6]([CH2:7]N2CCN(C(OC(C)(C)C)=O)CC2)=[CH:5][CH:4]=1)#[N:2].[C:23]([N:30]1[CH:34]=[CH:33][N:32]=[CH:31]1)([N:25]1C=CN=C1)=[S:24].[CH2:35](Cl)Cl>C(O)(C(F)(F)F)=O.CO>[C:1]([C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:32]2[CH2:33][CH2:34][N:30]([C:23](=[S:24])[NH2:25])[CH2:35][CH2:31]2)=[CH:5][CH:4]=1)#[N:2]A solution of tert-butyl 4-(4-cyanobenzyl)piperazine-1-carboxylate (336, 1.374 g, 4.56 mmol) in DCM (5 mL) and TFA (5 mL) was stirred at room temperature for one hour. The reaction mixture was concentrated and the residue was added to a solution of thiocarbonyldiimidazole (1.21 g, 6.84 mmol, 1.5 equiv.) in dry DCM (20 mL) under N2 at 0° C. Obtained solid was diluted with MeOH (20 mL) and transferred to a pressure vial. Ammonia gas was bubbled in for 10 min and the flask was capped and stirred at 80° C. for two days. The reaction mixture was concentrated and purified by flash chromatography using 60% EtOAc in hexane as an eluent, to afford the title compound 337 (593 mg, 50% yield). MS: calc: 260.1; found: 261.2 (M+H)
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