Trifluoroacetic acid → 7-Methoxy-4-((6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline

HRID 40228

Reaktionsgleichung

Reaktionsgleichung von HRID 40228
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[N:7]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[N:35][N:36]([CH:38]3[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]3)[CH:37]=2)O1.C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[CH3:24][O:23][C:19]1[CH:18]=[C:17]2[C:22]([C:13]([O:12][CH2:11][C:8]3[N:6]4[N:7]=[C:2]([C:33]5[CH:34]=[N:35][N:36]([CH:38]6[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]6)[CH:37]=5)[CH:3]=[CH:4][C:5]4=[N:10][N:9]=3)=[CH:14][CH:15]=[N:16]2)=[CH:21][CH:20]=1

Komponenten

8

Edukt 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinolineHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

Produkt 1

HCID 576909647-Methoxy-4-((6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

In a 50 mL sealable flask was charged with PdCl2(dppf)-CH2Cl2 adduct (0.011 g, 0.013 mmol), 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (0.150 g, 0.44 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.18 g, 0.48 mmol), sat NaHCO3 (0.75 ml, >0.97 mmol) and 4 mL dioxane. The vessel was sealed and the mixture heated at 80 C for 22 h. The mixture was allowed to cool to rt and diluted with EtOAc, the organic layer washed with water, sat. NaHCO3, dried over Na2SO4, filtered and evaporated. The residue was dissolved in 5 mL CH2Cl2 and TFA (1.20 ml, 16 mmol) was added. The mixture was stirred at rt for 10 min and evaporated. The residue was taken up into CH2Cl2 and stirred with minimal 2N NaOH for 1 h (ph basic). The mixture was evaporated and purified by prep hplc. The title compound was obtained as an off-white solid. M/Z=457.3 [M+H], calc 456.5076 for C24H24N8O2.

Aufarbeitung

  1. customThe vessel was sealed
  2. temperaturethe mixture heated at 80 C for 22 h
  3. washthe organic layer washed with water, sat. NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in 5 mL CH2Cl2
  8. customevaporated
  9. stirringstirred with minimal 2N NaOH for 1 h (ph basic)
  10. customThe mixture was evaporated
  11. custompurified by prep hplc

Quellen und Nachweise

ORD-Eintrag
ord-23847bd0af004f2ea6301592397be770
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524900B2

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