Glycine → HCID 54721168, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(2-cyclopropylethyl)-2H-pyrido[2,3-d][1,3]oxazine-2,4 (1H)-dione (Prepared according to PCT Int. Appl. (2003), WO 2003059356 A2)(0.232 g, 1.00 mmol) and diethylmalonate (0.152 mL, 1.00 mmol) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (0.300 mL, 2.00 mmol). 1,4-dioxane (1.0 mL) was added and the solution was heated to 150° C. for 20 min. in a Biotage Initiator microwave synthesizer (http://www.biotage.com). Following cooling, glycine (0.113 g, 1.50 mmol) was added and the solution was heated to 200° C. for 20 min. in a Biotage Initiator microwave synthesizer. The reaction mixture was then cooled, treated with 6M aqueous sodium hydroxide (2.0 mL), diluted with water and extracted with diethyl ether. The aqueous layer was then acidified with 6M aqueous hydrochloric acid and extracted twice with ethyl acetate. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo. The mixture was 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 white solid (0.008 g; 2.4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.0 (s, 1H), 10.5 (t, J=5.6 Hz, 1H), 8.83 (dd, J=4.5, 1.8 Hz, 1H), 8.46 (dd, J=8.0, 1.9 Hz, 1H), 7.43 (dd, J=8.0, 4.7 Hz, 1H), 4.41-4.60 (m, 2H), 4.13 (d, J=5.6 Hz, 2H), 1.55 (q, J=7.3 Hz, 2H), 0.67-0.82 (m, 1H), 0.32-0.41 (m, 2H), −0.09-0.04 (m, 2H). MS(ES+) m/e 332 [M+H]+.

Provenance & Evidence