反应 #1484869

反应方程式

2-((8-bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)-isoindoline-1,3-dione

2,8-dichloroquinoline-3-carbaldehyde

2-((2,8-dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione

bromide

→

(8-chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine

2-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione

溶剂

dioxane

反应条件

后处理

1. 1
   其他was purged with N2
2. 2
   温度the reaction was cooled to it
3. 3
   其他quenched with NH4Cl solution
4. 4
   workup.ADDITIONAfter work up, The residue containing
5. 5
   workup.ADDITIONa mixture of 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid
6. 6
   workup.ADDITIONwas treated with NH2NH2 (31 μL) in EtOH (1 mL)
7. 7
   温度at reflux
8. 8
   其他After usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1)

实验过程

2-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione was prepared in the similar manner as 2-((8-bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)-isoindoline-1,3-dione from 2,8-dichloroquinoline-3-carbaldehyde. A mixture of 2-((2,8-dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione (71 mg, 0.2 mmol), 2-pyridylzine bromide (0.5 M, 0.8 mL, 2.0 eq) and tetrakis(triphenylphosphine) palladium (11 mg, 5%) in dioxane (3 mL) was purged with N2 and heated to 65° C. After 12 h, the reaction was cooled to it and quenched with NH4Cl solution. After work up, The residue containing a mixture of 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid was treated with NH2NH2 (31 μL) in EtOH (1 mL) at reflux. After usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1) to give a pale yellow solid as (8-chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (d, J=8.0 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.17 (s, 1H), 7.84 (t, J=8.0 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.38 (t, J=8.0 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 4.13 (s, 3H). Mass Spectrum (ESI) m/e=270 (M+1).

来源