Hydrochloric Acid → 3-(4-(2-(5-Amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonic acid
Reaction equation
Cl.[NH2:2][C:3]1[C:12]2[N:11]=[CH:10][C:9]([CH2:13][CH2:14][C:15]3[CH:32]=[CH:31][C:18]([O:19][CH2:20][CH2:21][CH2:22][P:23](=[O:30])([O:27]CC)[O:24]CC)=[CH:17][C:16]=3[CH3:33])=[CH:8][C:7]=2[C:6]2[CH:34]=[CH:35][C:36]([CH3:38])=[CH:37][C:5]=2[N:4]=1>>[NH2:2][C:3]1[C:12]2[N:11]=[CH:10][C:9]([CH2:13][CH2:14][C:15]3[CH:32]=[CH:31][C:18]([O:19][CH2:20][CH2:21][CH2:22][P:23](=[O:24])([OH:27])[OH:30])=[CH:17][C:16]=3[CH3:33])=[CH:8][C:7]=2[C:6]2[CH:34]=[CH:35][C:36]([CH3:38])=[CH:37][C:5]=2[N:4]=1Participants
3
Conditions
- Temperature
- 100 °C
Procedure
A 12 N solution of hydrochloric acid (0.10 M) was added to diethyl 3-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonate (from Example 149) and the resulting mixture was allowed to stir at 100° C. for 18 hours. At this point, hydrochloric acid was removed under reduced pressure and the resulting residue was purified by RP-HPLC using a 10-50% MeCN in water gradient. The resulting trifluoroacetate salt was then converted to the free base form by the addition of a saturated aqueous solution of sodium bicarbonate, followed by washing three times with ethyl acetate. The combined organic layers were dried with anhydrous Na2SO4, and the volatiles were removed in vacuo to deliver 3-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonic acid as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 9.72 (br, 1H), 9.01 (s, 1H), 8.96 (br, 1H), 8.85 (s, 1H), 8.54 (d, 1H), 7.54 (s, 1H), 7.42 (d, 1H), 7.08 (d, 1), 6.74 (s, 1H), 6.66 (d, 1H), 3.95 (t, 2H), 3.14 (t, 2H), 2.97 (t, 2H), 2.50 (s, 3H), 2.27 (s, 3H), 1.81-1.91 (m, 2H), 1.56-1.67 (m, 2H). LRMS [M+H]=466.2