Hydrochloric Acid → Diethyl[(6-aminopyridin-3-yl)methyl]phosphonate

Temperature

110 °C

A mixture of di-tert-butyl [5-(bromomethyl)pyridin-2-yl]imidodicarbonate (Compound 309B, 1.162 g, 3 mmol) and triethyl phosphite (0.598 g, 3.6 mmol) in dioxane (2 mL) was stirred at 110° C. for 4 h. The cooled reaction mixture (room temperature) was treated with 4 N HCl in dioxane (5 mL) and DCM (10 mL) and allowed to stir at room temperature for 6 h. Sat. NaHCO3(aq, 15 mL) was added and the mixture was extracted with DCM (3×40 mL). The combined organic phases were dried over MgSO4, concentrated, and purified by silica gel chromatography (5% 7 N ammonia in MeOH in DCM) to afford 227 mg of the title compound (yield: 31%). 1H NMR (CDCl3, 400 MHz): δ=1.29 (t, J=6.8 Hz, 6 H), 2.98 (d, J=20.8 Hz, 2H), 4.02-4.09 (m, 4 H), 5.65 (s, br, 2 H), 6.58 (d, J=8.8 Hz, 1 H), 7.51 (dt, J=2.4, 8.8 Hz, 1H), 7.82 (t, J=2.4 Hz, 1 H). MS (ES+): m/z 245.09 [MH+]. HPLC: tR=0.70 min (UPLC TOF, polar—3 min).

1. customThe cooled reaction mixture (room temperature)
2. stirringto stir at room temperature for 6 h
3. extractionthe mixture was extracted with DCM (3×40 mL)
4. dry with materialThe combined organic phases were dried over MgSO4
5. concentrationconcentrated
6. custompurified by silica gel chromatography (5% 7 N ammonia in MeOH in DCM)

ORD record

ord-c7569cf1005545a4b2ebf5a27d2fa5b4

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096624B2