177760-04-2

A solution of N-formyl sarcosine ethyl ester in an equal mixture of ethyl formate and THF with cyclohexane was added slowly to NaH (60% wt in mineral oil) at RT. After that, the hydrogen release stopped, and the reaction mixture was unde-stirred for 3.5 h. The reaction mixture was concentrated under a vacuum and then suspended in a solution of EtOH containing concentrated aq.HCl 32%. After refluxing for 2 h, the hot reaction mixture was filtered and the resulting solid was washed with boiling EtOH. The filtrate was concentrated under vacuum and diluted with a mixture of EtOH/water. The pH was adjusted to 3, using an aqueous 5M solution of NaOH, and cyanamide was added. The resulting mixture was refluxed for 1.5 h, then cooled to rt and concentrated under reduced pressure to approximately 1/8 of the initial volume. The pH of the remaining solution was adjusted to 9-10 with a saturated aqueous solution of potassium carbonate, after cooling in an ice-water bath. The precipitate formed was removed by filtration, washed with water, and dried under vacuum at 40 °C overnight to afford Ethyl 2-amino-1-methyl-1H-imidazole-5-carboxylate as a pale yellow to orange solid.

[1] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 51 - 67