1-Hydroxybenzotriazole → (2R)-2-{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]benzamido}-2-[p-(carboxy-methyl)phenyl]acetic acid

Participants

Reaction Steps

A solution of (R)-α-amino-p-carboxymethylphenylacetic acid (0.1 g, 0.48 mmol) and bis trimethylsilyl acetamide (0.195 g, 0.96 mmol in 5 ml of DMF) was stirred for 20 minutes at room temperature. To the solution was then added pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivalyloxymethyl-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, followed by N-hydroxybenzotriazole (10 mg) and the stirring was maintained for a further 5 hours. The reaction mixture was then evaporated to dryness and the crude material redissolved in ether. The ether layers were extracted with NaHCO3. The aqueous layers were acidified to pH 2.5 with 2N HCl and the precipiate was filtered off, washed with water and dried under vacuum to give (2R)-2-{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]benzamido}-2-[p-(carboxy-methyl)phenyl]acetic acid (0.19 g), 85%) as a white solid;

Provenance & Evidence