Hydrochloric Acid → Diethyl[(6-aminopyridin-3-yl)methyl]phosphonate
Reaction equation
C(OC([N:8]([C:16]1[CH:21]=[CH:20][C:19]([CH2:22]Br)=[CH:18][N:17]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.[P:24]([O:31]CC)([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27].Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.C(Cl)Cl>[CH2:26]([O:25][P:24]([CH2:22][C:19]1[CH:18]=[N:17][C:16]([NH2:8])=[CH:21][CH:20]=1)(=[O:31])[O:28][CH2:29][CH3:30])[CH3:27]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 110 °C
Procedure
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, 6H), 2.98 (d, J=20.8 Hz, 2 H), 4.02-4.09 (m, 4H), 5.65 (s, br, 2H), 6.58 (d, J=8.8 Hz, 1H), 7.51 (dt, J=2.4, 8.8 Hz, 1H), 7.82 (t, J=2.4 Hz, 1H). MS (ES+): m/z 245.09 [MH+]. HPLC: tR=0.70 min (UPLC TOF, polar—3 min).
Workup
- customThe cooled reaction mixture (room temperature)
- stirringto stir at room temperature for 6 h
- extractionthe mixture was extracted with DCM (3×40 mL)
- dry with materialThe combined organic phases were dried over MgSO4
- concentrationconcentrated
- custompurified by silica gel chromatography (5% 7 N ammonia in MeOH in DCM)
Sources & evidence
- ORD record
- ord-9a36c9b592984926ba72ef0c2f09534f
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08399433B2
Reaction notes
Loading…