Glycine → HCID 54721171, compound

Participants

Reaction Steps

A solution of the compound from Example 4a) (0.480 g, 1.89 mmol) in dichloromethane (20.0 mL) was treated with triethylamine (0.410 mL, 2.97 mmol) followed by ethyl malonyl chloride (0.370 mL, 2.97 mmol). The mixture was stirred at ambient temperature for 1.5 h, followed by addition of water, and extraction twice with dichloromethane. The combined organic portions were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in ethanol (2.0 mL) and treated with sodium ethoxide (0.880 mL, 2.27 mmol, 21% solution in ethanol) at ambient temperature and stirred for 3 h. The solution was concentrated in vacuo and treated with water and 1N aqueous hydrochloric acid. The resulting solid was filtered, washed with water, and dried in vacuo. A solution of this solid (0.533 g, 1.60 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL, 1.60 mmol) and glycine (0.12 g, 1.60 mmol) in ethanol (3.0 mL) was heated to 180° C. for 30 min. in a Biotage Initiator microwave synthesizer. The solution was concentrated in vacuo and purified via preparative HPLC(YMC 75×30 mm column, 0.1% TFA in water and 0.1% TFA in acetonitrile) to afford the title compound as a light orange solid (0.113 g, 20%). 1H NMR (400 MHz, METHANOL-d4) δ ppm 13.0 (br. S., 1H), 10.5 (t, J=5.6 Hz, 1H), 8.80 (dd, J=4.5, 1.8 Hz, 1H), 8.57 (dd, J=7.8, 1.8 Hz, 1H), 7.44 (dd, J=8.0, 4.7 Hz, 1H), 7.17-7.41 (m, 5H), 5.77 (s, 2H), 4.24 (d, J=5.3 Hz, 2H). MS(ES+) m/e 354 [M+H]+.

Provenance & Evidence