反応 #10507

反応方程式

5-bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole

Cs2CO3

CsF

4-cyanophenylboronic acid

2-dicyclohexylphosphino(biphenyl)

→

title compound

収率 44.9%

4-{2-[2-(2-(R)-Methyl-pyrrolidin-1-yl)-ethyl]-1H-indol-5-yl}-benzonitrile

収率 44.9%

溶媒

H2O

toluene

反応条件

後処理

1. 1
   その他The resulting mixture was purged with nitrogen
2. 2
   その他The resulting reaction mixture
3. 3
   その他was consumed
4. 4
   温度The reaction mixture was cooled to room temperature
5. 5
   workup.ADDITIONIPAc (20 mL) was added
6. 6
   その他The organic layer was separated
7. 7
   濃縮concentrated
8. 8
   その他The residue was purified by column chromatography
9. 9
   洗浄eluting with heptane/acetone/CH2Cl2/Et3N (600 mL/40 mL/5 mL/2 mL)
10. 10
    workup.ADDITIONThe fractions containing product
11. 11
    濃縮concentrated under reduced pressure

実験手順

A reaction flask was charged with Cs2CO3 (1.14 g, 3.5 mmol), CsF (0.38 g, 2.5 mmol), 4-cyanophenylboronic acid (425 mg, 2.5 mmol), and H2O (10 mL) followed by a toluene solution (10 mL) of 5-bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole (307 mg, 1.0 mmol). The resulting mixture was purged with nitrogen. To the reaction mixture was then added 2-dicyclohexylphosphino(biphenyl) (35 mg, 0.1 mmol) and Pd2(dba)3 (46 mg, 0.05 mmol). The resulting reaction mixture was then heated to 65° C. overnight under nitrogen after which HPLC indicated that all the 5-bromo-2-[2-(-(R)-methyl-pyrrolidin-1-yl-ethyl]-1H-indole was consumed. The reaction mixture was cooled to room temperature and IPAc (20 mL) was added. The organic layer was separated and concentrated. The residue was purified by column chromatography eluting with heptane/acetone/CH2Cl2/Et3N (600 mL/40 mL/5 mL/2 mL). The fractions containing product were combined and concentrated under reduced pressure to provide the title compound as a semi-solid (148 mg). 1H NMR (400 MHz, CDCl3) δ 10.22 (s, 1H), 7.65–7.74 (m, 5H), 7.40 (d, J=8.5 Hz, 1H), 7.33 (dd, J=1.8, 8.5 Hz, 1H), 6.27 (s, 1H), 3.37–3.42 (m, 1H), 3.21–3.25 (m, 1H), 3.01–3.16 (m, 2H), 2.54–2.62 (m, 2H), 2.33 (q, J=8.78Hz, 1H), 2.04–2.08 (m, 1H), 1.80–1.93 (m, 2H), 1.56–1.63 (m, 1H), 1.21 (d, J=6.2 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ 146.99, 139.96, 135.61, 132.05, 130.30, 128.74, 127.32, 120.02, 119.13, 118.36, 111.13, 109.16, 99.49, 61.25, 53.68, 53.57, 32.92, 26.21, 22.14, 18.98. [M+H]+ at m/z 330.

出典