Reaction #2122542

Reaction equation

HATU

(S)-2-chloro-5-(2-(pyrrolidin-2-yl)-1H-imidazol-5-yl)pyrimidine trihydrochloride

2-(pyridin-3-yl)acetic acid

DIEA

→

title compound

Yield 25.0%

5-(2-chloropyrimidin-5-yl)-1H-imidazol 2-(pyrrolidin-1-yl)-2-(pyridin-3-yl)ethanone

Yield 25.0%

Solvents

DMF

DMF

Conditions

Workup

1. 1
   Otherwas removed in vacuo
2. 2
   Washfollowed by step gradient elution with 0% B to 0% B for 150 mL

Procedure

HATU (0.60 g, 1.57 mmol) was added in one portion to a stirred solution of intermediate (S)-2-chloro-5-(2-(pyrrolidin-2-yl)-1H-imidazol-5-yl)pyrimidine trihydrochloride (0.46 g, 1.43 mmol, theoretical amount), 2-(pyridin-3-yl)acetic acid (0.25 g, 1.43 mmol) and DIEA (1.0 mL, 5.72 mmol) in anhydrous DMF (10 mL) at ambient temperature. The mixture was stirred at room temperature for 2 h before the DMF was removed in vacuo. The residue was taken up in CH2Cl2 and subjected to Biotage™ flash chromatography on silica gel (40M column, preequilibration with 0% B for 600 mL followed by step gradient elution with 0% B to 0% B for 150 mL followed by 0% B to 15% B for 1500 mL followed by 15% B to 25% B for 999 mL where B=MeOH and A=CH2Cl2). There was isolated the title compound (0.131 g, 25%, 2 steps) as a yellow solid.

Source