Morpholine → Tert-butyl (2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate

Participants

Reaction Steps

4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)-1-(oxetan-3-yl)piperazine-2-carboxylate, lithium salt (200 mg, 0.452 mmol) was azeotroped 3× with toluene and 4 Å molecular sieves were added. THF (3 mL) was added, followed by DIPEA (0.118 mL, 0.677 mmol), morpholine (0.117 mL, 1.355 mmol), and T3P (0.538 mL, 0.903 mmol). The reaction was stirred at rt for 1 h. The reaction mixture was filtered through a small pad of celite, rinsing with EtOAc. The solvent was removed in vacuo and the material was purified by flash column chromatography (0-4% MeOH/DCM). Tert-butyl (2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate (112 mg) was obtained as an off-white solid.

Provenance & Evidence