反応 #44294

反応方程式

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

収率 91.3%

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

収率 91.3%

溶媒

dimethoxyethane

water

反応条件

後処理

1. 1
   その他After degassed several times
2. 2
   その他the reaction mixture was degassed again
3. 3
   温度the reaction mixture was cooled down to R.T.
4. 4
   workup.ADDITIONdiluted with water (10 ml)
5. 5
   ろ過filtered
6. 6
   抽出The aqueous layer was extracted with CH2Cl2 (2×50 ml) EtOAc (1×10 ml)
7. 7
   乾燥was dried with K2CO3
8. 8
   ろ過filtered
9. 9
   ろ過filtered initially
10. 10
    濃縮concentrated under reduced pressure
11. 11
    その他The resulting residue was purified via flash column chromatography
12. 12
    洗浄eluted with 0-7% CH2Cl2

実験手順

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).

出典