Reaction #68611

Reaction equation

sodium 2-chloro-2,2-difluoroacetate

4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol hydrobromide

cesium carbonate

DMF

→

7-(difluoromethoxy)-4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinoline

Yield 13.4%

Solvents

formic acid

Conditions

Workup

1. 1
   Otherflushed with argon
2. 2
   Othersealed
3. 3
   Otherplaced in a 100° C.
4. 4
   Otherfor 5 hours
5. 5
   ConcentrationThe reaction mixture was concentrated
6. 6
   workup.ADDITIONdiluted with DCM and chloroform
7. 7
   WashThis was washed with water, sat. NaHCO3, and brine
8. 8
   Dryingdried with MgSO4
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated
11. 11
    Otherto give a brown oil
12. 12
    OtherThis was purified by HPLC

Procedure

A 48 mL tube was charged with sodium 2-chloro-2,2-difluoroacetate (0.15 g, 1.0 mmol), 4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol hydrobromide (0.200 g, 0.44 mmol), cesium carbonate (0.43 g, 1.3 mmol), and DMF (1.7 ml, 22 mmol), flushed with argon, sealed, then placed in a 100° C. oil bath for 5 hours. The reaction mixture was concentrated, then diluted with DCM and chloroform. This was washed with water, sat. NaHCO3, and brine, then dried with MgSO4, filtered, and concentrated to give a brown oil. This was purified by HPLC to give 7-(difluoromethoxy)-4-((6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinoline (0.025 g, 13% yield) as the formic acid salt. MS (ESI pos. ion) m/z: 424 (MH+). Calc'd exact mass for C21H15F2N5O3: 423.

Source