Reaction #172035

Reaction equation

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

5-amino-3-methylisothiazole hydrochloride

K2CO3

BINAP

→

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

Yield 27.9%

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-methoxypropanamide (52 mg, 0.164 mmol), 5-amino-3-methylisothiazole hydrochloride (40 mg, 0.265 mmol), K2CO3 (110 mg, 0.797 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (25 mg, 0.111 mmol) in dioxane (2 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-methoxypropanamide (16 mg).

Source