Reaction #10493

Reaction equation

K2CO3

CsF

4-cyanophenyl boronic acid

2-dicyclohexylphosphinobiphenyl

5-bromo-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazole

→

4-{2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazol-5-yl}-benzonitrile

Yield 31.5%

Solvents

toluene

Conditions

Workup

1. 1
   OtherThe resulting mixture was purged with nitrogen
2. 2
   OtherThe resulting reaction mixture
3. 3
   WashAt completion, the reaction was washed with water
4. 4
   workup.ADDITIONdiluted with with CH2Cl2
5. 5
   Otherpurified by column chromatography (silica gel, 10% MeOH/CH2Cl2)

Procedure

To a reaction flask containing K2CO3 (0.326 g, 1.5 mmol), CsF (0.233 g, 1.5 mmol), and (0.19 g, 1.3 mmol) of 4-cyanophenyl boronic acid was added a solution of 5-bromo-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazole (0.25 g, 0.77 mmol) in 3 mL of toluene. The resulting mixture was purged with nitrogen, and then 2-dicyclohexylphosphinobiphenyl (54 mg, 0.15 mmol) and Pd2(dba)3 (70 mg, 0.08 mmol) were added. The resulting reaction mixture was then heated at 90° C. for 2 hr. At completion, the reaction was washed with water, then diluted with with CH2Cl2, and purified by column chromatography (silica gel, 10% MeOH/CH2Cl2), to give 4-{2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazol-5-yl}-benzonitrile in an isolated yield of 31.5%. The hydrochloride salt of the product was formed by adding 6N HCl (2 equivalents) in isopropanol solution and then diluting with 1 mL of isopropanol, followed by removal of solvent. 1H NMR (400 MHz, Methanol d4) δ 1.47 (d, J=6.45 Hz, 3 H) 1.72 (dd, J=12.76, 8.37 Hz, 1 H) 2.29 (m, 2 H) 3.23 (m, 3 H) 3.36 (t, J=7.14 Hz, 1 H) 3.62 (m, 3 H) 3.99 (m, 1 H) 7.68 (dd, J=8.44, 1.72 Hz, 1 H) 7.77 (m, 4 H) 8.01 (d, J=8.37 Hz, 1 H) 8.17 (d, J=1.51 Hz, 1 H) [M+H]+ at m/z 348.

Source