3-Pyridinylboronic acid → dimethyl 5-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]pentane-1-sulfonamide

HRID 9429

Reaktionsgleichung

Reaktionsgleichung von HRID 9429
[CH3:1][C:2]([CH3:30])([S:26]([NH2:29])(=[O:28])=[O:27])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][C:15](Br)=[CH:14][C:13]=3[N:12]=[C:11]([NH2:21])[C:10]=2[N:9]=[C:8]1[CH2:22][O:23][CH2:24][CH3:25].[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]([CH3:30])([S:26]([NH2:29])(=[O:28])=[O:27])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][C:15]([C:33]4[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=4)=[CH:14][C:13]=3[N:12]=[C:11]([NH2:21])[C:10]=2[N:9]=[C:8]1[CH2:22][O:23][CH2:24][CH3:25]

Komponenten

4

Edukt 2

HCID 27343783-Pyridinylboronic acid2×HCID 68819084Dimethyl 5-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentane-1-sulfonamide

Produkt 1

HCID 68818764dimethyl 5-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]pentane-1-sulfonamideAusbeute 34,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator

Versuchsvorschrift

Dimethyl 5-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentane-1-sulfonamide (0.26 g, 0.53 mmol) and pyridine-3-boronic acid (0.78 g, 0.63 mmol) were coupled according to the method described in Part J of Example 1. The reaction was heated at 100° C. for 31 hours, at which time additional palladium acetate (0.002 equivalent) was added. Heating was resumed for 14 hours, and then additional pyridine-3-boronic acid (0.3 equivalent) was added. The reaction was heated for another 22 hours. The work-up procedure used in Part F of Examples 125–135 was followed. The crude product was purified twice by HPFC (eluting with chloroform:CMA in a gradient from 100:0 to 80:20) and then triturated with ethyl acetate and isolated by filtration. The product was finally recrystallized from isopropanol, isolated by filtration, and dried for eight hours under high vacuum at 100° C. to provide 0.090 g of dimethyl 5-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]pentane-1-sulfonamide as a white powder, mp 159–160° C.

Aufarbeitung

  1. additionwas added
  2. temperatureHeating
  3. temperatureThe reaction was heated for another 22 hours
  4. customThe crude product was purified twice by HPFC (
  5. washeluting with chloroform
  6. customCMA in a gradient from 100:0 to 80:20) and then triturated with ethyl acetate
  7. customisolated by filtration
  8. customThe product was finally recrystallized from isopropanol
  9. customisolated by filtration
  10. customdried for eight hours under high vacuum at 100° C.

Quellen und Nachweise

ORD-Eintrag
ord-0cf36a9b9fe846209e97efb76af17162
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091214B2

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