Reaction #172016

Reaction equation

(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-4-methylpentanamide

5-amino-3-methylisothiazole hydrochloride

BINAP

K2CO3

→

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

Solvents

dioxane

Conditions

Workup

1. 1
   Otherwas degassed with Ar
2. 2
   workup.ADDITIONWater and EtOAc were added
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)-4-methylpentanamide (175 mg, 0.533 mmol), 5-amino-3-methylisothiazole hydrochloride (97 mg, 0.644 mmol), BINAP (50 mg, 0.080 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (250 mg, 1.81 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 120 C for 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)-4-methylpentanamide as a crude residue.

Source