Hydrochloric Acid → HCID 89813167, Verbindung

HRID 1481106Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481106
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])[CH3:2].[C:27]([Cu])#[N:28].N#N.Cl>C(Cl)Cl.CN1C(=O)CCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:27]#[N:28])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])[CH3:2]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 89812883HCID 89812883, VerbindungHCID 178418546HCID 178418546, Verbindung

Produkt 1

HCID 89813167HCID 89813167, VerbindungAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A 20-mL scintillation vial was charged with 1-bromo-4-hydroxy-7-(4-fluoro-2-chloro-phenoxy)-isoquinoline-3-carboxylic acid ethyl ester (340 mg, 0.77 mmol), CuCN (138 mg, 1.54 mmol) and NMP (1.8 mL). It was filled with N2 gas and close-capped. The mixture was stirred in a 130° C. oil bath for 3 h. Reaction mixture was diluted with CH2Cl2 (100 mL) and stirred at room temperature for 3 days. To the mixture was added 100 mL of 0.5 N HCl aq. solution. It was stirred vigorously for 3 min. Two phases were separated. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexanes to provide the title compound 231 mg (0.60 mmol) in 78% yield. 1H NMR (200 MHz) in CDCl3, δ ppm: 12.42 (s, 1H), 8.45 (d, J=8.8 Hz, 1H), 7.54 (dd, J=9.2, 2.6 Hz, 1H), 7.40-7.10 (m, 4H), 4.58 (q, J=7.0 Hz, 2H), 1.51 (t, J=7.0 Hz, 3H).

Aufarbeitung

  1. customclose-capped
  2. customReaction mixture
  3. stirringstirred at room temperature for 3 days
  4. stirringIt was stirred vigorously for 3 min
  5. customTwo phases were separated
  6. washOrganic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrude product was purified by silica gel chromatography
  11. washeluting with 5-50% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-9bd66f965f5746409c96cd1d2c928ccb
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409892B2

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