Ethyl Acetate → HCID 57791842, Verbindung

HRID 1091778Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1091778
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:23])[NH:7][N:8]=[C:9]2[CH2:12][C:13]2[CH:14]=[CH:15][C:16]([F:22])=[C:17]([CH:21]=2)[C:18]([OH:20])=O)=[CH:4][CH:3]=1.[CH3:24][O:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.C(OCC)(=O)C>CN(C=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][CH:3]=1)[C:6](=[O:23])[NH:7][N:8]=[C:9]2[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17]([C:18]([N:29]2[CH2:30][CH2:31][CH:26]([O:25][CH3:24])[CH2:27][CH2:28]2)=[O:20])[CH:21]=1

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 776664-MethoxypiperidineHCID 81531DiisopropylethylamineHCID 57791829HCID 57791829, Verbindung

Produkt 1

HCID 57791842HCID 57791842, VerbindungAusbeute 5,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

5-((7-bromo-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-2-fluorobenzoic acid (97) (1.0 g, 2.65 mmol), 4-methoxypiperidine (0.336 g, 2.92 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.936 g, 2.92 mmol) were dissolved in DMF (40 mL), to this was added DIPEA (0.509 mL, 2.92 mmol) and the reaction was stirred for 1 hour. The DMF was evaporated and the crude gum was quenched with 2M NaOH (75 mL), extracted with EtOAc (3×75 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a brown gum. The gum was passed through a plug of silica eluting with ethyl acetate to afford a white solid, most of which was used without further purification. A sample (100 mg) was purified via preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (66 mg); 1H NMR (400.132 MHz, CDCl3) δ 1.62-1.48 (1H, m), 1.85-1.68 (2H, m), 1.94-1.89 (1H, m), 3.18-3.07 (1H, m), 3.35 (3H, s), 3.47-3.40 (2H, m), 3.67-3.53 (1H, m), 4.06-3.89 (1H, m), 4.23 (2H, s), 7.04 (1H, t), 7.31-7.26 (2H, m), 7.86-7.84 (2H, m), 8.33-8.31 (1H, m), 10.55 (1H, s); m/z (LC-MS, ESI+), RT=1.94 (M+H 476).

Aufarbeitung

  1. customThe DMF was evaporated
  2. customthe crude gum was quenched with 2M NaOH (75 mL)
  3. extractionextracted with EtOAc (3×75 mL)
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a brown gum
  8. customto afford a white solid
  9. custommost of which was used without further purification
  10. customA sample (100 mg) was purified via preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-e4caaacbaee24955943e92e5929c0b54
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129380B2

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