4-Methylmorpholine → (S)-4-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)-5-(benzyloxy)-5-oxopentanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoic acid (38.4 mg, 0.129 mmol) in 5 mL of DMF was added N-methylmorpholine (40.4 mg, 0.399 mmol), followed by the addition of 2-chloro-4,6-dimethoxy-1,3,5-triazine (22.64 mg, 0.129 mmol). The resulting mixture was stirred for 1.5 hours at 25° C., at which time HPLC showed that the reaction was complete. L-glutamic acid γ-benzyl ester (30.6 mg, 0.129 mmol) was added, and stirring was continued at 25° C. until complete conversion of precursor was determined by HPLC (around two hours). To the reaction mixture was added 10 mL of methylene chloride and 10 ml of deionized water, and the mixture was stirred for 15 minutes. The layers were separated. The aqueous layer was extracted with DCM (10 ml×2). The organic phases were combined. The solution was concentrated on rotary-evaporator under reduced pressure. The resulting residue was subjected to flash chromatography on a Biotage system. Yield: 55 mg, 82%. 1HNMR in d6-DMSO, δ ppm: 10.61 (1H, s), 10.20 (1H, s), 8.72 (1H, d, J=10 Hz), 7.78 (2H, d, J=5 Hz), 7.35 (5H, m), 7.30 (2H, m), 6.30 (1H, s), 6.07 (2H, s), 5.14 (2H, s), 3.86 (1H, m), 2.97 (2H, t), 2.84 (2H, t), 2.20 (2H, s), 2.02 (1H, m), 1.95 (1H, m). ESI-MS: 518 [M+H]+.

Provenance & Evidence