Reaction #41579

Reaction equation

methylpyrazin-2-imidate

methanesulfonic acid

4-(2-chloro-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine

4-(2-chlorophenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine

→

compound

5-(2-Chloro-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Solvents

N-methylpyrrolidinone

Conditions

Workup

1. 1
   Otherthe reaction liquid
2. 2
   OtherThe reaction liquid
3. 3
   Otherwas purified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]
4. 4
   workup.ADDITIONThe solvent of the resulting fraction was diluted with ethyl acetate
5. 5
   Washwashed with aqueous saturated sodium bicarbonate
6. 6
   Dryingdried with anhydrous sodium sulfate
7. 7
   OtherThe solvent was evaporated away under reduced pressure

Procedure

15 mg of methylpyrazin-2-imidate (pyrazine-2-carboximidic acid methyl ester) and 0.0065 ml of methanesulfonic acid were added to an N-methylpyrrolidinone (0.5 ml) solution of 38 mg of 4-(2-chloro-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 204 (step 1), and the reaction liquid was stirred at 120° C. for 20 minutes. The reaction liquid was purified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]. The solvent of the resulting fraction was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, and then dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure to obtain the entitled compound as a yellow solid.

Source