Lithium diisopropylamide → (E)-Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1-fluorovinylphosphonate

HRID 2167656Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2167656
[F:1][CH:2]([P:11](=[O:18])([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])P(=O)(OCC)OCC.[Li+].CC([N-]C(C)C)C.[NH2:27][C:28]1[C:37]2[N:36]=[CH:35][C:34]([CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=3[CH3:48])=[CH:33][C:32]=2[C:31]2[CH:49]=[CH:50][C:51]([CH:53]=O)=[CH:52][C:30]=2[N:29]=1>C1COCC1>[NH2:27][C:28]1[C:37]2[N:36]=[CH:35][C:34]([CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=3[CH3:48])=[CH:33][C:32]=2[C:31]2[CH:49]=[CH:50][C:51](/[CH:53]=[C:2](/[P:11](=[O:18])([O:12][CH2:13][CH3:14])[O:15][CH2:16][CH3:17])\[F:1])=[CH:52][C:30]=2[N:29]=1

Komponenten

5

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 10935649Tetraethyl (fluoromethylene)bis(phosphonate)HCID 581665185-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde

Produkt 1

HCID 86651455(E)-Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1-fluorovinylphosphonate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a stirred solution of tetraethyl fluoromethylenediphosphonate (2.5 equiv.) in THF (0.27 M) cooled at −78° C. was added LDA solution (1.8 M in ethylbenzene/pentane/hexane, 2.0 equiv.). The resulting reaction mixture was warmed up to room temperature and stirred for 30 minutes, before it was cooled back down to −78° C. A solution of 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (2-2) (Example 9−Step 1) (1.0 equiv.) in THF (0.18 M) was added, and the reaction mixture was allowed to warm up to room temperature slowly. The reaction was quenched with saturated NH4Cl solution. Aqueous phase was extracted with DCM (3×). The combined organic phases were combined and concentrated in vacuo. The residue was purified by a COMBIFLASH® system (ISCO) using a gradient of 0-5% MeOH/DCM to provide (E)-Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1-fluorovinylphosphonate (3-2) as a colorless solid.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. temperaturewas cooled back down to −78° C
  3. temperatureto warm up to room temperature slowly
  4. customThe reaction was quenched with saturated NH4Cl solution
  5. extractionAqueous phase was extracted with DCM (3×)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a COMBIFLASH® system (ISCO)

Quellen und Nachweise

ORD-Eintrag
ord-2812e61500454826a9e82bdeb93efc47
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045470B2

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