1,2-Dichloroethane → (4S)-tert-butyl 3-((8-carbamoylquinolin-5-yl)carbamoyl)-4-(3-fluorophenyl)pyrrolidine-1-carboxylate

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Reaction Steps

To a solution of tert-butyl(3R,4S)-4-(3-fluoro-phenyl)-pyrrolidine-1,3-dicarboxylate (125.00 mg; 0.40 mmol; 1.00 eq.) in DCE (4.0 ml) bis(2-oxo-1,3-oxazolidin-3-yl)phosphinic chloride (102.87 mg; 0.40 mmol; 1.00 eq.) was added. After stirring for 15 mins at RT, DIEA (0.15 ml; 0.81 mmol; 2.00 eq.) and 5-aminoquinoline-8-carboxamide (75.65 mg; 0.40 mmol; 1.00 eq) were added. The reaction mixture was stirred overnight at 60° C. The crude was purified by prep HPLC to yield (4S)-tert-butyl 3-((8-carbamoylquinolin-5-yl)carbamoyl)-4-(3-fluorophenyl)pyrrolidine-1-carboxylate, which was added 1 ml 4.0M HCl and 1 ml methanol, stirred at RT for 3 h. The reaction mixture was concentrated, neutralized to Ph 7 and purified by prep HPLC to afford Example 27. (M+H=479, obsd=479).

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