Reaction #169027

Reaction equation

guanidine HCl

sodium methoxide

2-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-3-phenylamino-acrylonitrile

guanidine HCl

sodium methoxide

→

5-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-pyrimidine-2,4-diamine

Yield 80.2%

Solvents

ethanol

EtOH

water

ethanol

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was heated
2. 2
   Temperatureto reflux for 2 hours
3. 3
   TemperatureThe reaction mixture was cooled
4. 4
   Extractionextracted twice with EtOAc
5. 5
   Washwashed with brine
6. 6
   Dryingdried over magnesium sulfate
7. 7
   OtherSolvent was removed in vacuo

Procedure

2-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-3-phenylamino-acrylonitrile (360 mg, 1 mmol), guanidine HCl (411 mg, 4 mmol) and sodium methoxide (880 ul, 4 mmol, 4.9 M solution in methanol) in 5 mL absolute ethanol were heated to reflux in 5 ml absolute ethanol for 2 hours. Premixed guanidine HCl (411 mg, 4 mmol) and sodium methoxide (880 ul, 4 mmol, 4.9 M solution in methanol) in 1 ml EtOH was added via pipette, and the reaction mixture was heated to reflux for 2 hours. The reaction mixture was cooled, diluted with water, extracted twice with EtOAc, washed with brine, and dried over magnesium sulfate. Solvent was removed in vacuo to give 241 mg of 5-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-pyrimidine-2,4-diamine as a white solid (74%). Mass Spec M+H=301, M.P.=181° C. Recrystallization of 175 mg of this product from MeOH and HCl/diethyl ether afforded 98 mg of the corresponding HCl salt 49%., Mass Spec M+H=301, M.P. >300 C.

Source