Synthesis
1. Preparation of ethyl 2-amino-1H-pyrrole-3-carboxylate. Ethyl 3-amino-3-iminopropionate (390 mg, 3.0 mmol) was dissolved in ethyl acetate (20 mL) under argon protection with vigorous stirring. Anhydrous chloroacetaldehyde was added rapidly at 22 °C. The reaction mixture was stirred for 10 minutes and then heated to reflux for 20 minutes. Cool to room temperature and filter through a silica gel column (15 g). The residue in the reaction flask was washed several times with ethyl acetate (20 mL x 5) and the filtrates were combined. The filtrate was concentrated under reduced pressure to give 120 mg of light yellow solid product in 47% yield. The product was characterized as follows: 1H NMR (500 MHz, CDCl3) δ (ppm): 7.92 (br, 1H), 6.28 (t, J = 2.8 Hz, 1H), 6.15 (dd, J = 2.0 Hz, 1H), 4.94 (br, 2H), 4.24 (q, J = 7.1 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H).13C NMR (125 MHz, CDCl3) δ (ppm): 166.5, 145.4, 110.3, 107.5, 94.5, 59.3, 14.7.
References
[1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 5, p. 1555 - 1560
[2] Patent: WO2017/4408, 2017, A1. Location in patent: Paragraph 0087; 0089; 0090
[3] Patent: WO2016/73891, 2016, A1. Location in patent: Paragraph 00204
[4] Patent: US9447100, 2016, B2. Location in patent: Page/Page column 556; 557
