Reaction #41726

Reaction equation

diamine

tert-butyl 4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylate

4-bromophenyl isothiocyanate

1-ethyl-(3-dimethylaminopropyl)carbodiimide HCl

→

product

tert-butyl 4-{2-[(4-bromophenyl)amino]-1-methylbenzimidazol-5-yloxy}pyridine-2-carboxylate

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe reaction was evaporated under reduced pressure
2. 2
   workup.ADDITIONdiluted with ethyl acetate and water
3. 3
   ExtractionThe aqueous layer was back extracted with ethyl acetate
4. 4
   WashThe combined organic layers were washed with water and brine
5. 5
   DryingThe organic layer was dried over anhydrous sodium sulfate
6. 6
   Otherlater evaporated under reduced pressure
7. 7
   OtherThe crude material was purified

Procedure

A solution of the diamine from step 6 (1 eq) and 4-bromophenyl isothiocyanate (1 eq) in anhydrous tetrahydrofuran under nitrogen was stirred at 20° C. for 2-3 hours or when determined to be complete by HPLC. The solution was treated with 3 equivalents of 1-ethyl-(3-dimethylaminopropyl)carbodiimide HCl. The stirred solution was heated to 50° C. under nitrogen for 2-3 hrs or until the reaction is determined to be complete by HPLC. The reaction was evaporated under reduced pressure and then diluted with ethyl acetate and water. The aqueous layer was back extracted with ethyl acetate. The combined organic layers were washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and later evaporated under reduced pressure. The crude material was purified by reverse high-pressure liquid chromatography to afford the product as a brown powder after lyophlization. MS: MH+=495.

Source