Reaction #172096

Reaction equation

(R)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamate

p-toluidine

BINAP

Cs2CO3

→

(R)-benzyl 1-(1-(5-cyano-3-fluoro-6-(p-tolylamino)pyridin-2-ylamino)propyl)cyclopropylcarbamate

Yield 67.6%

Solvents

dioxane

Conditions

Workup

1. 1
   OtherAfter degassed with Argon
2. 2
   workup.ADDITIONThe mixture was diluted with dioxane, precipitate
3. 3
   Filtrationwas filtered off
4. 4
   Filtrationfilter cake
5. 5
   Washwas washed with ACN
6. 6
   Concentrationthe filtrate was concentrated
7. 7
   Otherpurified by column

Procedure

To a solution of (R)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamate (100 mg, 0.25 mmol) in dioxane (1.5 mL) was added p-toluidine (32 mg, 0.30 mmol), BINAP (31 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol) and Cs2CO3 (244.5 mg, 0.75 mmol). After degassed with Argon, the mixture was heated at 80° C. for 5 h. The mixture was diluted with dioxane, precipitate was filtered off, filter cake was washed with ACN, the filtrate was concentrated and purified by column to give of (R)-benzyl 1-(1-(5-cyano-3-fluoro-6-(p-tolylamino)pyridin-2-ylamino)propyl)cyclopropylcarbamate (80 mg).

Source