Ammonia → (2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid amide

Participants

Reaction Steps

80 mg (2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid are placed in 2.00 ml N,N-dimethylformamide and combined with 86.77 mg diisopropylethylamine and 76.20 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 334 μl ammonia solution (0.5 M in dioxane) are added. The reaction mixture is stirred for 3 hours at ambient temperature, then acidified and water is added. The diastereomers are separated by preparative HPLC (method B). 11.7 mg of Diastereomer 1 and 15.3 mg of Diastereomer 2 (Example 128) are obtained as powders. Analytical HPLC-MS (method A): Diastereomer 1, RT=1.49 min, Diastereomer 2. RT=1.49 min.

Provenance & Evidence