Ethyl orthoformate → HCID 57515551, Verbindung

HRID 44781

Reaktionsgleichung

Reaktionsgleichung von HRID 44781
[NH2:1][C:2]1[C:3]([Cl:28])=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]1([OH:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:30]1C([N+]([O-])=O)=C(Cl)C2C(=CC=CC=2)N=1.ClC1C2C(=CC=CC=2)N=CC=1[N+]([O-])=O.Cl.N1C=CC=CC=1.C(OC(OCC)OCC)C>C1(C)C=CC=CC=1>[Cl:28][C:3]1[C:2]2[N:1]=[CH:30][N:12]([CH2:13][C:14]3([OH:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][CH2:15]3)[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1

Komponenten

7

Edukt 5

HCID 31214Ethyl orthoformate2×HCID 27851382,4-Dichloro-3-nitroquinolineHCID 10176127Pyridinium chlorideHCID 112758084-Chloro-3-nitroquinolineHCID 57515550HCID 57515550, Verbindung2×

Produkt 1

HCID 57515551HCID 57515551, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Under a nitrogen atmosphere, tert-butyl 4 {[(3-amino-2-chloroquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate (0.25 g, 0.61 mmol, prepared according to the general methods of Example 4 Parts A through D using 2,4-dichloro-3-nitroquinoline in lieu of 4-chloro-3-nitroquinoline in Part C), toluene (5 mL), pyridine hydrochloride (0.02 g), and triethylorthoformate (0.11 mL, 0.65 mmol) was heated at reflux for 2 hours. More triethylorthoformate (0.5 eq) was added and the reaction mixture was heated for an additional hour. The reaction was rerun in the same manner using 5.25 g of tert-butyl 4 {[(3-amino-2-chloroquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate. The small and larger scale reaction mixtures were combined and washed with water (50 mL). The aqueous layer was extracted with dichloromethane (2×100 mL). The organic layers were combined and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel eluting with a gradient of 0-10% methanol in ethyl acetate) to provide 4.08 g of tert-butyl 4-[(4-chloro-1H-imidazo[4,5-c]quinolin-1-yl)methyl]-4-hydroxypiperidine-1-carboxylate as a tan frothy solid.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperaturethe reaction mixture was heated for an additional hour
  4. customThe small and larger scale reaction mixtures
  5. washwashed with water (50 mL)
  6. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (silica gel eluting with a gradient of 0-10% methanol in ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-0c4daffce4da4e3c88a0b888541fc707
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541438B2

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