Bromotrimethylsilane → (E)-2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonic acid

HRID 2167653Notes

Reaction equation

HRID 2167653 reaction equation
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25](/[CH:27]=[CH:28]/[P:29](=[O:36])([O:33]CC)[O:30]CC)=[CH:26][C:4]=2[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25](/[CH:27]=[CH:28]/[P:29](=[O:30])([OH:33])[OH:36])=[CH:26][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86651453(E)-diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonate

Product 1

HCID 49838386(E)-2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (E)-diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonate (3-1) (1.0 equiv.) in DCM (0.095 M) at 0° C. was added TMSBr (10 equiv.). The reaction was warmed to room temperature over 2 hours, and then quenched with small amounts of MeOH. The DCM was removed by evaporation, and then added DMSO/water. The mixture was adjusted to pH 9 and directly purified on RP-HPLC using a C18 column, eluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient. The fractions containing the product were combined and concentrated in vacuo to give the (E)-2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonic acid (10) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 9.76 (s, 1H), 9.33 (s, 1H), 9.03 (s, 1H), 8.82 (s, 1H), 8.60 (d, 1H, J=8.4 Hz), 7.87 (d, 1H, J=8.4 Hz), 7.78 (s, 1H), 7.31 (dd, 1H, J=17.6, 21.6 Hz), 7.03 (d, 1H, J=8.4 Hz), 6.69 (m, 2H), 6.61 (dd, 1H, J=2.8, 8.4 Hz), 3.64 (s, 3H), 3.14-3.06 (m, 2H), 2.97-2.91 (m, 2H), 2.23 (s, 3H). LRMS [M+H]=450.2

Workup

  1. customquenched with small amounts of MeOH
  2. customThe DCM was removed by evaporation
  3. customdirectly purified on RP-HPLC
  4. washeluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient
  5. additionThe fractions containing the product
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-adb011bee05544fc924d219387f67d96
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

Loading…