반응 #44294

반응 방정식

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

수율 91.3%

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

수율 91.3%

용매

dimethoxyethane

water

반응 조건

후처리

1. 1
   기타After degassed several times
2. 2
   기타the reaction mixture was degassed again
3. 3
   온도the reaction mixture was cooled down to R.T.
4. 4
   workup.ADDITIONdiluted with water (10 ml)
5. 5
   여과filtered
6. 6
   추출The aqueous layer was extracted with CH2Cl2 (2×50 ml) EtOAc (1×10 ml)
7. 7
   건조was dried with K2CO3
8. 8
   여과filtered
9. 9
   여과filtered initially
10. 10
    농축concentrated under reduced pressure
11. 11
    기타The resulting residue was purified via flash column chromatography
12. 12
    세척eluted with 0-7% CH2Cl2

실험 절차

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).

출처