反应详情

HATU (180 mg, 0.47 mmol) was added to a solution of 6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanoic acid (187 mg, 0.4 mmol, Example 44), 4-methylmorpholine (0.2 mL, 1.8 mmol), and DMF (2 mL). After 5 min, this solution was added to Gly-OEt•HCl (65 mg, 0.47 mmol). After 75 min, the reaction was poured into 1M KH2PO4 (30 mL) and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (1:4→0:1; hexanes:ethyl acetate) to give ethyl 2-(6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)hexanamido)acetate: 1H NMR (400 MHz, DMSO-d6): δ 9.51 (s, 1H), 8.81 (s, 2H), 8.21 (t, 1H), 7.94 (d, 1H), 7.20 (d, 1H), 4.63 (s, 1H), 4.05 (q, 2H), 3.97 (t, 2H), 3.92 (s, 3H), 3.77 (d, 2H), 2.14 (t, 2H), 1.68 (m, 2H), 1.55 (m, 2H), 1.44 (m, 2H), 1.16 (t, 3H); MS (ESI): 552.0.

1. waitAfter 75 min
2. extractionextracted with ethyl acetate (40 mL×2)
3. customThe combined extracts were dried
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified by silica gel chromatography (1:4→0:1; hexanes:ethyl acetate)