Hydrochloric Acid → n-[(4-Hydroxy-2-oxo-1,2-dihydro-1,7-naphthyridin-3-yl)carbonyl]glycine

A solution of ethyl 3-aminoisonicotinate (0.071 g, 0.43 mmol) in methylene chloride (2.0 mL) was treated with triethylamine (1.00 mL, 7.17 mmol) followed by ethyl malonyl chloride (0.060 mL, 0.47 mmol). The mixture was stirred overnight at ambient temperature, followed by concentration in vacuo. The residue was dissolved in ethanol (2.0 mL), treated with sodium ethoxide (0.158 mL, 0.43 mmol, 21% solution in ethanol) at ambient temperature, and stirred overnight. The solution was concentrated in vacuo, and the resulting residue was dissolved in ethanol (2.0 mL) and treated with glycine sodium salt (0.030 g, 0.43 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.060 mL, 0.43 mmol) and heated to 180° C. for 30 min. in a Biotage Initiator microwave synthesizer. The reaction was diluted with water, acidified with 1 N aqueous hydrochloric acid, and the resulting precipitate was filtered, washed with water, and dried in vacuo to afford the title compound as a light brown solid (0.034 g, 30%). 1H NMR (400 MHz, DMSO-d6 δ ppm 12.4 (s, 2H), 10.4 (s, 2H), 8.88 (s, 1H), 7.89 (s, 1H), 4.15 (d, J=5.6 Hz, 2H). MS(ES+) m/e 264 [M+H]+.

1. concentrationfollowed by concentration in vacuo
2. dissolutionThe residue was dissolved in ethanol (2.0 mL)
3. stirringstirred overnight
4. concentrationThe solution was concentrated in vacuo
5. dissolutionthe resulting residue was dissolved in ethanol (2.0 mL)
6. temperatureheated to 180° C. for 30 min. in a Biotage Initiator microwave synthesizer
7. filtrationthe resulting precipitate was filtered
8. washwashed with water
9. customdried in vacuo

ORD record

ord-61741bdb304a4dd2b228fecefa72ff4f

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897612B2