Ethyl N-methoxy-N-methylcarbamate → 3-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine-8-carboxylic acid methoxy-methyl-amide

HRID 226115

Reaktionsgleichung

Reaktionsgleichung von HRID 226115
[F:1][C:2]1[CH:22]=[CH:21][C:5]2[S:6][C:7]([C:10]3[N:14]4[N:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]4=[N:12][C:11]=3[CH3:20])=[C:8]([CH3:9])[C:4]=2[CH:3]=1.[CH3:23][O:24][N:25]([CH3:31])[C:26](=O)[O:27]CC.[Li+].CC([N-]C(C)C)C>C1COCC1>[CH3:23][O:24][N:25]([CH3:31])[C:26]([C:18]1[C:13]2[N:14]([C:10]([C:7]3[S:6][C:5]4[CH:21]=[CH:22][C:2]([F:1])=[CH:3][C:4]=4[C:8]=3[CH3:9])=[C:11]([CH3:20])[N:12]=2)[N:15]=[C:16]([CH3:19])[CH:17]=1)=[O:27]

Komponenten

5

Edukt 3

HCID 533715Ethyl N-methoxy-N-methylcarbamateHCID 2724682Lithium diisopropylamideHCID 688598503-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

Produkt 1

HCID 866210453-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine-8-carboxylic acid methoxy-methyl-amideAusbeute 31,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

The solution of 3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (2.09 g, 6.73 mmol) in THF (56 mL) is stirred at −78° C. Ethyl N-methoxy-N-methylcarbamate (4.48 g, 33.7 mmol) is added. LDA (10 mL, 20.1 mmol) is added dropwise to maintain reaction temperature at −75° C. The reaction is stirred at −78° C. for 1 hour. The mixture is quenched with H2O, filtered through celite with CH2Cl2. The collect solution is washed with H2O, dried over Na2SO4, filtered and concentrated. The crude is purified by ISCO (50-100% EtOAc/Hexane) to give the title compound (0.85 g, 31%). 1H NMR (CDCl3): δ 7.8 (dd, J=4.8, 8.5 Hz, 1H), 7.5 (dd, J=2.5, 9.7 Hz, 1H), 7.2 (m, 1H), 7.0 (s, 1H), 3.7 (s, 3H), 3.5 (s, 3H), 2.6 (s, 3H), 2.55 (s, 3H), 2.3 (s, 3H) ppm. MS (m/e): 399 (100%, M+1).

Aufarbeitung

  1. temperatureto maintain
  2. customreaction temperature at −75° C
  3. customThe mixture is quenched with H2O
  4. filtrationfiltered through celite with CH2Cl2
  5. washThe collect solution is washed with H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude is purified by ISCO (50-100% EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-8fc792b35b1541978efcda4e44742859
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557103B2

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