Trimethylsilyl iodide → 2-(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid

HRID 2167651Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2167651
[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]([C:27](=[O:39])[C:28]([P:31](=[O:38])([O:35]CC)[O:32]CC)([F:30])[F:29])=[CH:26][C:4]=2[N:3]=1.[Si](I)(C)(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]([C:27](=[O:39])[C:28]([P:31](=[O:32])([OH:35])[OH:38])([F:29])[F:30])=[CH:26][C:4]=2[N:3]=1

Komponenten

4

Edukt 2

HCID 85247Trimethylsilyl iodide2×HCID 86651452Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate

Produkt 1

HCID 498383852-(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate (2-4) (1.0 equiv.) in DCM (0.05 M) at 0° C. was added TMSI (5.0 equiv.). The reaction was warmed to room temperature over 2 hours, and more TMSI was added (2.5 equiv.). The reaction was stirred for another 30 minutes, and then quenched with small amounts of water. 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 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonic acid (9) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 8.82 (s, 1H), 8.5 (br, 1H), 8.44 (s, 1H), 8.2 (br, 1H), 7.98 (d, 1H, J=8.2 Hz), 7.2 (br, 2H), 7.05 (d, 1H, J=8.3 Hz), 6.73 (s, 1H), 6.67 (d, 1H, J=8.3 Hz), 3.70 (s, 3H), 2.99-2.87 (m, 4H), 2.25 (s, 3H). LRMS [M+H]=502.2

Aufarbeitung

  1. customquenched with small amounts of water
  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

Quellen und Nachweise

ORD-Eintrag
ord-ccdd8d443e324ecdb5570d0a6d6afb90
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045470B2

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