Reaction #44294

Reaction equation

6-[(6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl]-7-fluoroquinoline

4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester

CsF

CH2Cl2

→

desired product

Yield 91.3%

7-fluoro-6-{[6-(1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl]methyl}-quinoline

Yield 91.3%

Solvents

dimethoxyethane

water

Conditions

Workup

1. 1
   OtherAfter degassed several times
2. 2
   Otherthe reaction mixture was degassed again
3. 3
   Temperaturethe reaction mixture was cooled down to R.T.
4. 4
   workup.ADDITIONdiluted with water (10 ml)
5. 5
   Filtrationfiltered
6. 6
   ExtractionThe aqueous layer was extracted with CH2Cl2 (2×50 ml) EtOAc (1×10 ml)
7. 7
   Dryingwas dried with K2CO3
8. 8
   Filtrationfiltered
9. 9
   Filtrationfiltered initially
10. 10
    Concentrationconcentrated under reduced pressure
11. 11
    OtherThe resulting residue was purified via flash column chromatography
12. 12
    Washeluted with 0-7% CH2Cl2

Procedure

To a suspension of 6-[(6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl]-7-fluoroquinoline (250 mg, 0.696 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (225 mg, 0.766 mmol) in dimethoxyethane (8.0 ml) was added CsF (317 mg, 2.09 mmol) and water (1.05 ml) at R.T. After degassed several times, to the suspension, 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium (11) 1:1 complex with CH2Cl2 (25.5 mg, 0.04 mmol) was added and the reaction mixture was degassed again. After stirring at 85° C. for 16 h, the reaction mixture was cooled down to R.T. diluted with water (10 ml) and filtered. The aqueous layer was extracted with CH2Cl2 (2×50 ml) EtOAc (1×10 ml). The combined the organic layer was dried with K2CO3 filtered and combined this with the solid filtered initially, and concentrated under reduced pressure. The resulting residue was purified via flash column chromatography eluted with 0-7% CH2Cl2:MeOH to give the desired product (220 mg 91%). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.18 (s, 2H) 7.53 (dd, J=8.21, 4.17 Hz, 2H) 7.84 (d, J=11.37 Hz, 1H) 8.17 (d, J=8.59 Hz, 1H) 8.29 (s, 1H) 8.41-8.46 (m, 1H) 8.70 (s, 1H) 8.92 (dd, J=4.29, 1.77 Hz, 1H) 9.25 (s, 1H).

Source