Triethyl Phosphate → HCID 49838510, compound

HRID 2167659Notes

Reaction equation

HRID 2167659 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][CH:34]=1)[CH2:5][O:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][CH2:12][C:13]2[CH:14]=[N:15][C:16]3[C:21]([CH:22]=2)=[C:20]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:19]2=[N:18][C:17]=3[NH2:28])=[C:9]([CH3:31])[CH:8]=1.[P:35](OCC)([O:40]CC)([O:37]CC)=[O:36].C[Si](Br)(C)C>C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:28][C:17]1[C:16]2[N:15]=[CH:14][C:13]([CH2:12][CH2:11][C:10]3[CH:29]=[CH:30][C:7]([O:6][CH2:5][C:4]4[CH:3]=[C:2]([P:35](=[O:36])([OH:40])[OH:37])[CH:34]=[CH:33][CH:32]=4)=[CH:8][C:9]=3[CH3:31])=[CH:22][C:21]=2[C:20]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:19]=2[N:18]=1

Participants

6

Reactant 3

HCID 6535Triethyl PhosphateHCID 76113BromotrimethylsilaneHCID 58166520HCID 58166520, compound

Product 1

HCID 49838510HCID 49838510, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 2-(4-(3-iodobenzyloxy)-2-methylphenethyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine (1.0 equiv.) in triethyl phosphate (1.05 eq.) was added palladium acetate (0.08 eq.). The resulting reaction mixture was heated at 90° C. overnight. After the reaction was cooled down to room temperature, the residue was taken up in DCM (0.27 M) at 0° C., and was treated with TMSBr (11 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 3-((4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)methyl)phenylphosphonic acid (13) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 8.84 (s, 1H), 8.72 (s, 1H), 8.35 (d, 1H, J=8.4 Hz), 7.67 (d, 1H, J=12 Hz), 7.60-7.54 (m, 1H), 7.30-7.20 (m, 2H), 7.15 (d, 1H, J=8.4 Hz), 7.11 (d, 1 H, J=8.4 Hz), 7.04 (s, 1H), 6.84 (s, 1H), 6.77 (m, 1H), 4.99 (s, 2H), 3.12-2.92 (m, 4H), 2.44 (s, 3 H), 2.27 (s, 3H). LRMS [M+H]=514.2

Workup

  1. customThe resulting reaction mixture
  2. temperatureAfter the reaction was cooled down to room temperature
  3. temperatureThe reaction was warmed to room temperature over 2 hours
  4. customquenched with small amounts of MeOH
  5. customThe DCM was removed by evaporation
  6. customdirectly purified on RP-HPLC
  7. washeluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient
  8. additionThe fractions containing the product
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fcfb575a9acd42b9b2ab555f034542cc
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

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