Reaction #306258

Reaction equation

HATU

2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)benzoic acid

(Z)-N′-hydroxyacetamidine

→

4-((6-(3-chloro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

Solvents

DMF

DMF

water

Conditions

Workup

1. 1
   workup.STIRRINGStirred for an additional 30 min
2. 2
   FiltrationIsolated product by filtration
3. 3
   OtherSplit into 3 portions
4. 4
   Otherseparately took up in dioxane (4 mL) in a microwave tube
5. 5
   ConcentrationConcentrated
6. 6
   OtherPurified on RPHPLC
7. 7
   workup.ADDITIONTook fractions containing product
8. 8
   Otherwas isolated by filtration

Procedure

HATU (0.370 g, 0.974 mmol) and 2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)benzoic acid (0.300 g, 0.650 mmol) were taken up in DMF (5 mL). Added Hunig'sBase (0.339 ml, 1.95 mmol). Stirred for 10 min. Added (Z)-N′-hydroxyacetamidine (0.289 g, 3.90 mmol). Stirred for an additional 30 min. Removed DMF in vacuo. Suspended in water. Isolated product by filtration. The resulting solid was allowed to try under vacuum. Split into 3 portions and separately took up in dioxane (4 mL) in a microwave tube and heated for 12 min at 150° C. Combined all 3 reactions. Concentrated. Purified on RPHPLC. Took fractions containing product and made basic with 9% sodium carbonate. Removed volatiles in vacuo. Product crashed out and was isolated by filtration. MS m/z=500.0 [M+1]+. Calc'd for C25H18ClN7O3: 499.1.

Source