Hydrochloric Acid → (2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid

Participants

Reaction Steps

To a solution of (S)-α-amino-p-carboxymethylphenylacetic acid (0.1 g, 0.48 mmol) and pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzoate (0.213 g, 0.4 mmol), prepared as described in Example 2, in 5 ml of DMF was added bistrimethyl silyl acetamide (BSA) (0.194 g, 0.96 mmol). After stirring under N2 for 20 minutes N-methylmorpholine was added (0.081 g, 0.8 mmol) followed by N-hydroxybenzotriazole (HOBT) (0.01 g). The reaction mixture was stirred at room temperature for 4 hours and evaporated to dryness. The solid obtained by trituration with ether and filtration was resuspended in a mixture of methanol/water (2 ml) and the pH adjusted to 2.5 with 2N HCl . The resulting precipitate was filtered off, washed with water and dried to give (2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid (140 mg, 64%) as a yellow solid;

Provenance & Evidence