2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert butyl ester 3-ethyl ester

Synthesis

General Steps: Step a. Synthesis of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl 3-ethyl ester In anhydrous ethanol (50 mL), N-tert-butoxycarbonyl-4-piperidone (12.9 g), ethyl cyanoacetate (7.345 g), and sulfur powder (2.080 g) were mixed, followed by the addition of triethylamine (9 mL). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the precipitate was collected by filtration and washed with ethanol to afford 2-amino-4,5-dihydrothieno[2,3-c]pyridine-3,6(7H)-dicarboxylic acid-6-tert-butyl ester (18.7 g, 88% yield). Product characterization data: 1H NMR (300 MHz, CDCl3): δ 6.02 (s, 2H), 4.31 (s, 2H), 4.23 (q, 2H, J = 7.2 Hz), 3.58 (t, 2H, J = 6.0 Hz), 2.72-2.80 (br s, 2H), 1.44 (s, 9H), 1.30 (t, 3H, J = 7.2 Hz). LC-MS (ESI) m/z: 327.0 (M + H)+.

References

[1] Synlett, 2010, # 9, p. 1351 - 1354
[2] Patent: US2010/120805, 2010, A1. Location in patent: Page/Page column 44
[3] Journal of Medicinal Chemistry, 2010, vol. 53, # 20, p. 7316 - 7326
[4] Patent: WO2009/33581, 2009, A1. Location in patent: Page/Page column 62
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3101 - 3112