Yield:582306-90-9 84%

Reaction Conditions:

with lithium hexamethyldisilazane in tetrahydrofuran at 0 - 20; for 16 h;Inert atmosphere;

Steps:

22 Example 22: 5-(7-chloro-1 ,2,3,4-tetrahydronaphthalen-2-yl)-2-(2-chloro-4-fluorophenyl)- 4,5,6,7-tetrahydro-3/-/-imidazo[4,5-c]pyridine

The solution of 2-chloro-4-fluorobenzonitrile (5 g, 32 mmol) in diethyl ether (100 ml_) was dropwise added to LiHMDS (1 M in tetrahydrofuran, 64 ml_) with stirring under nitrogen atmosphere at 0 °C. The resulting solution was stirred at 0 °C ~ room temperature for 16 hrs. The resulting solution was quenched with 3N hydrochloric acid (100 ml_) at 0 °C. The water phase was collected, the pH of the water phase was adjusted to 14 with NaOH aqueous, and extracted with ethyl acetate (100 ml_x3). The combined organic phases were washed with brine (100 ml_), dried over anhydrous Na₂S0₄ and evaporated in vacuo. This resulted in 2-chloro-4-fluorobenzimidamide (4.6 g, 84 % yield) as a brown solid. MS (ESI): mass calcd. for C₇H₆CIFN₂ 172.02, m/z found 172.9 [M+H]⁺.

References:

WO2020/106751,2020,A1 Location in patent:Paragraph 0183