반응 #68506

반응 방정식

TFA

4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

NaHCO3

→

title compound

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

용매

dioxane

EtOAc

반응 조건

후처리

1. 1
   기타The vessel was sealed
2. 2
   온도the mixture heated at 80 C for 22 h
3. 3
   세척the organic layer washed with water, sat. NaHCO3
4. 4
   건조dried over Na2SO4
5. 5
   여과filtered
6. 6
   기타evaporated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in 5 mL CH2Cl2
8. 8
   기타evaporated
9. 9
   workup.STIRRINGstirred with minimal 2N NaOH for 1 h (ph basic)
10. 10
    기타The mixture was evaporated
11. 11
    기타purified by prep hplc

실험 절차

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.

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