Reaction #172065

Reaction equation

(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide

5-amino-3-methylisothiazole hydrochloride

K2CO3

BINAP

→

(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide

Yield 38.9%

Solvents

dioxane

Conditions

Workup

1. 1
   Otherwas degassed with argon
2. 2
   ConcentrationThe mixture was concentrated in vacuo
3. 3
   OtherThe residue was purified by HPLC

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide (125 mg, 0.344 mmol), 5-amino-3-methylisothiazole hydrochloride (80 mg, 0.531 mmol), K2CO3 (220 mg, 1.59 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (30 mg, 0.133 mmol) in dioxane (3 mL) was degassed with argon, then was stirred at 120 C for 18 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide (53 mg).

Source