Reaction #172007

Reaction equation

5-amino-3-methylisothiazole hydrochloride

(R)-2-(3-bromo-4-cyanophenylamino)-3-cyclohexylpropanamide

BINAP

K2CO3

→

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

Yield 99.1%

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
   Otherthe organic phase was separated
5. 5
   Washwashed with 1N HCl
6. 6
   Dryingwith 5% NaHCO3, dried over Na2SO4
7. 7
   Concentrationconcentrated in vacuo

Procedure

A mixture of (R)-2-(3-bromo-4-cyanophenylamino)-3-cyclohexylpropanamide (222 mg, 0.634 mmol), 5-amino-3-methylisothiazole hydrochloride (126 mg, 0.840 mmol), BINAP (60 mg, 0.096 mmol), Pd(OAc)2 (45 mg, 0.200 mmol) and K2CO3 (360 mg, 2.60 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 organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-cyclohexylpropanamide as a solid (241 mg).

Source