Reaction #172024

Reaction equation

(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide

5-amino-3-methylisothiazole hydrochloride

BINAP

K2CO3

→

(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide

Solvents

EtOAc

Water

dioxane

Conditions

Workup

1. 1
   Otherwas degassed with Ar
2. 2
   workup.STIRRINGThe mixture was stirred at 120 C for another 18 h
3. 3
   FiltrationAfter being filtered
4. 4
   Washthe filtrate was washed with water
5. 5
   Dryingdried over Na2SO4
6. 6
   Concentrationconcentrated in vacuo

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide (362 mg, 1.00 mmol), 5-amino-3-methylisothiazole hydrochloride (166 mg, 1.10 mmol), BINAP (70 mg, 0.112 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (430 mg, 3.11 mmol) in dioxane (5 mL) was degassed with Ar, then was stirred at 120 C for 18 h. More Pd(OAc)2 (35 mg, 0.156 mmol) was added. The mixture was stirred at 120 C for another 18 h. Water and EtOAc were added. After being filtered, the filtrate was washed with water, dried over Na2SO4, concentrated in vacuo to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide as a crude residue.

Source