[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:6]=1.[H-].[Na+].Cl[C:18]([O:20][CH2:21][CH2:22]Cl)=[O:19].O>O1CCCC1>[O:19]=[C:18]1[N:1]([C:2]2[S:3][CH:4]=[C:5]([C:7]3[CH:8]=[CH:9][C:10]([C:11]#[N:12])=[CH:13][CH:14]=3)[N:6]=2)[CH2:22][CH2:21][O:20]14-(2-Amino-thiazol-4-yl)-benzonitrile (1.5 g, 7.4 mmol), prepared in the previous step, in dry tetrahydrofuran (10 mL) was added dropwise to a suspension of sodium hydride (0.6 g, ˜15 mmol, 60% in oil) in dry tetrahydrofuran (10 mL) at room temperature. After 1 h, 2-chloroethyl chloroformate (0.83 mL, 8 mmol) was added dropwise and the mixture heated under reflux. After 16 h, the mixture was cooled, poured carefully into water, which was extracted with ethyl acetate. The organic layer was separated, dried (anhydrous Na2SO4), evaporated and the residue purified by silica gel column chromatography (ethyl acetate:hexane, 3:7) to afford the crude product. Recrystallization from ethanol gave the title compound (0.2 g, 10%), MS (ES) m/z 272 [M+H]+. HPLC 99.5% @ 210-370 nm, 99.3% @ 240 nm; RT=8.3 min, the Xterra® RP18 column, 3.5μ, 4.6×150 mm column 1.2 mL/min, 85/15-5/95 (Phos Buff. pH=2.1/ACN+MeOH) for 10 min, hold 4 min.
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