Reaction #172020

Reaction equation

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

5-amino-3-methylisothiazole hydrochloride

NaH

Water

→

titled compound

(R)-4-(1-amino-4-methyl-1-oxopentan-2-ylamino)-3-fluoro-2-(3-methylisothiazol-5-ylamino)benzamide

Solvents

DMSO

EtOAc

Conditions

Workup

1. 1
   OtherThe organic phase was separated
2. 2
   Dryingdried over Na2SO4
3. 3
   Concentrationconcentrated in vacuo
4. 4
   workup.ADDITIONTo a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added
5. 5
   workup.STIRRINGAfter being stirred at room temperature for 30 min
6. 6
   Concentrationthe mixture was concentrated in vacuo
7. 7
   Otherwas purified by HPLC

Procedure

To a solution of (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide (113 mg, 0.423 mmol) and 5-amino-3-methylisothiazole hydrochloride (70 mg, 0.464 mmol) in DMSO (3 mL), NaH (60% in mineral oil, 100 mg, 2.50 mmol) was added. H2 gas evolved. The mixture was stirred at 130 C for 30 min. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. To a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added. After being stirred at room temperature for 30 min, the mixture was concentrated in vacuo. The residue was acidified with HOAc (0.5 mL), and then was purified by HPLC to give the titled compound (36 mg). MS 380.4 (M+H); UV 202.2, 280.5 nm

Source