反应详情

A 0° C. solution of N-methylpyroglutamic acid (621 mg; 3.29 mmol; Bull Soc Chim Fr, 1973, (3) (Pt. 2), 1053-6), 3-methyl-4-(1-pyrrolidinylmethyl)phenyl 6-methoxy-2-(4-aminophenyl)benzo[b]thiophen-3-yl ketone (Example 1, Part E; 1.5 g; 3.29 mmol) and 1-hydroxy-7-azabenzotriazole (448 mg; 3.29 mmol) in 50 mL of dry DMF was treated with 1,3-dicyclohexylcarbodiimide (629 mg, 3.29 mmol). The resulting mixture was allowed to gradually warm to ambient temperature. After stirring for 48 h, the reaction mixture was poured into 100 mL of saturated NaHCO3. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with H2O (2×50 mL) and brine (50 mL), dried over K2CO3, filtered and concentrated in vacuo. Radial chromatography (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH) afforded 816 mg (1.4 mmol; 43%) of the title product as a bright yellow foam.

1. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
2. washThe combined organic layers were washed with H2O (2×50 mL) and brine (50 mL)
3. dry with materialdried over K2CO3
4. filtrationfiltered
5. concentrationconcentrated in vacuo