Reaction #172013

Reaction equation

HOAc

(R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide

5-amino-3-methylisothiazole hydrochloride

NaH

→

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

Yield 30.9%

Solvents

DMSO

Conditions

Workup

1. 1
   Otherthe mixture was purified by HPLC

Procedure

To a solution of (R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide (92 mg, 0.34 mmol) and 5-amino-3-methylisothiazole hydrochloride (70 mg, 0.46 mmol) in DMSO (2 mL), NaH (60% in mineral oil, 80 mg, 2.00 mmol) was added. H2 gas evolved. The mixture was stirred at 130 C for 1 h. After being acidified with HOAc (1.0 mL), the mixture was purified by HPLC to give (R)-2-(4-cyano-3-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide (38 mg).

Source