Reaktion #68495

Reaktionsgleichung

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

2-methylbut-3-yn-2-ol

triethylamine

acetonitrile

→

4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol

Ausbeute 51.3%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeflushed with argon
2. 2
   Sonstigesealed
3. 3
   Sonstigeplaced in a 90° C.
4. 4
   Sonstigefor 30 minutes
5. 5
   Sonstigethe tube flushed with argon
6. 6
   Sonstigesealed
7. 7
   FiltrationThe reaction mixture was filtered
8. 8
   Einengenconcentrated
9. 9
   Sonstigeto yield a dark brown oil
10. 10
    SonstigeThis was purified by MPLC
11. 11
    Wascheneluting with 1-7% MeOH/DCM over 40 minutes
12. 12
    SonstigeThe appropriate fractions were collected

Vorschrift

A 25×200 mm test tube was charged with 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (0.150 g, 0.439 mmol), 2-methylbut-3-yn-2-ol (0.213 ml, 2.19 mmol), copper (I) iodide (0.0209 g, 0.110 mmol), triethylamine (1.83 ml, 13.2 mmol), and acetonitrile (5.00 ml, 96.2 mmol), flushed with argon, sealed, and placed in a 90° C. oil bath for 30 minutes. PdCl2(dppf)-CH2Cl2Adduct (0.0358 g, 0.0439 mmol) was added in one portion, the tube flushed with argon, sealed, then heated in a 90° C. oil bath for 4 hours. The reaction mixture was filtered thru a pad of silica gel (eluting with EtOAc/DCM/MeOH), then concentrated to yield a dark brown oil. This was purified by MPLC, using a 40 g RediSep column, eluting with 1-7% MeOH/DCM over 40 minutes. The appropriate fractions were collected to give 4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol (0.0877 g, 51.3% yield).

Quelle