Hydrochloric Acid → 3-(4-(2-(5-Amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonic acid

HRID 340364Notes

Reaction equation

HRID 340364 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]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 58213570Diethyl 3-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonate

Product 1

HCID 581665143-(4-(2-(5-Amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)propylphosphonic acid

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

Workup

  1. customAt this point, hydrochloric acid was removed under reduced pressure
  2. customthe resulting residue was purified by RP-HPLC
  3. additionThe resulting trifluoroacetate salt was then converted to the free base form by the addition of a saturated aqueous solution of sodium bicarbonate
  4. washby washing three times with ethyl acetate
  5. dry with materialThe combined organic layers were dried with anhydrous Na2SO4
  6. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-42d963b1f4654cbd843c9c27366b9246
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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