Réaction #157296

Équation de réaction

{2-[4-(4-amino-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-(3-chloro-phenyl)-amine trifluoroacetate

6-aminonicotinic acid

trifluoroacetic acid

O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

HATU

→

product

Rendement 57.8%

6-amino-N-(4-{4-[4-(3-chloro-phenylamino)-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-2-yl]-piperazin-1-yl}-phenyl)-nicotinamide trifluoroacetate

Rendement 57.8%

Solvants

diisopropylethylamine

dimethylsulphoxide

diisopropylethylamine

water

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe reaction mixture is stirred for 16 hours at ambient temperature
2. 2
   workup.ADDITIONare added
3. 3
   AutreThe resulting salt is purified by preparative HPLC (method A)

Mode opératoire

200 mg of {2-[4-(4-amino-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-(3-chloro-phenyl)-amine trifluoroacetate are placed in 2.50 ml dimethylsulphoxide and combined with 100 μl diisopropylethylamine and 150 mg O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (HATU). The mixture is stirred for 0.25 hours at ambient temperature, then 50 mg 6-aminonicotinic acid in 100 μl diisopropylethylamine are added. The reaction mixture is stirred for 16 hours at ambient temperature, then acidified with trifluoroacetic acid and 2 ml of water are added. The resulting salt is purified by preparative HPLC (method A). 140 mg of the product are obtained as the trifluoroacetate. Analytical HPLC (method B): RT=2.74 min.

Source