Hydrochloric Acid → HCID 118045911, compound

To a mixture of trimethyl 2-(6-(tert-butoxycarbonylamino)pyridin-3-yl)propane-1,1,3-tricarboxylate (2.5 g, 6.1 mmol) and tetramethyl 2-(6-aminopyridin-3-yl)propane-1,1,1,3-tetracarboxylate (1.8 g, 4.9 mmol) in MeOH (30 mL) was added aqueous NaOH solution (2.44 g NaOH in 5 mL water, 60.9 mmol). The resulting mixture was heated to reflux by oil bath for 1 hour. The reaction mixture was cooled down to room temperature, and concentrated under reduced pressure via rotavap. To the concentrated residue were added water (15 mL) and conc. HCl (3 mL). The resulting mixture was heated to reflux overnight. The reaction mixture was cooled down, and concentrated under reduced pressure via rotavap, and a solid was obtained. The obtained solid residue was triturated with methanol (100 mL) and the precipitates was removed by filtration, and a light color filtrate was obtained. To the filtrate was added conc. HCl (200 μL) and the resulting mixture was heated to reflux via external oil bath for 1 h. The reaction mixture was cooled down, and concentrated. The residue was partitioned between EtOAc/sat. NaHCO3 (50 mL/50 mL). Aqueous layer was extracted with EtOAc (50 mL). The EtOAc extracts were combined, washed with brine (50 mL), dried over Na2SO4, and concentrated. A white solid was obtained as desired dimethyl 3-(6-aminopyridin-3-yl)pentanedioate (2.6 g, 10.31 mmol, 93.9% yield). LCMS (m/z) 253.2 (MH+) 0.38 min; 1H NMR (CDCl3) δ ppm 7.95 (d, J=2.3 Hz, 1H), 7.32 (dd, J=8.2, 2.3 Hz, 1H), 6.46 (d, J=8.6 Hz, 1H), 4.37 (br. s., 2H), 3.61 (s, 6H), 3.55 (quin, J=7.5 Hz, 1H), 2.80-2.66 (m, 2H), 2.65-2.51 (m, 2H).

1. temperatureThe resulting mixture was heated
2. temperatureto reflux by oil bath for 1 hour
3. concentrationconcentrated under reduced pressure via rotavap
4. additionTo the concentrated residue were added water (15 mL) and conc. HCl (3 mL)
5. temperatureThe resulting mixture was heated
6. temperatureto reflux overnight
7. temperatureThe reaction mixture was cooled down
8. concentrationconcentrated under reduced pressure via rotavap
9. customa solid was obtained
10. customThe obtained solid residue was triturated with methanol (100 mL)
11. customthe precipitates was removed by filtration
12. customa light color filtrate was obtained
13. temperaturethe resulting mixture was heated
14. temperatureto reflux via external oil bath for 1 h
15. temperatureThe reaction mixture was cooled down
16. concentrationconcentrated
17. customThe residue was partitioned between EtOAc/
18. extractionAqueous layer was extracted with EtOAc (50 mL)
19. washwashed with brine (50 mL)
20. dry with materialdried over Na2SO4
21. concentrationconcentrated

ORD record

ord-8098b20ab96e418ba55d35f42235be3c

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242996B2