Chemical Properties
White crystalline powder
Uses
N-Carbethoxyphthalimide is used in the synthetic preparation of a novel dual binders as potent, selective, and orally bioavailable tankyrase inhibitors.
Preparation
N-Carbethoxyphthalimide is prepared for: addition of Ethyl Chloroformate to a cold solution of Phthalimide and Triethylamine in DMF; alkylation of potassium phthalimide with ethyl chloroformate.
Synthesis
GENERAL METHOD: 3-Hydroxy-1H-isoindol-1-one (7.36 g, 50.00 mmol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 25 mL) and triethylamine (TEA, 9 mL, 65.00 mmol) was added. The reaction system was cooled to 0 °C, followed by slow dropwise addition of ethyl chloroformate (5.7 mL, 60.00 mmol). The reaction mixture was stirred at room temperature for 2 h and then poured into ice water. The precipitate was collected by filtration and the solid product was washed with cold water and dried to give N-ethoxycarbonylphthalimide (8.67 g, 79.1% yield) as a white solid. The melting point was 81.4-83.6 ℃. Nuclear magnetic resonance hydrogen spectrum (1H NMR, CDCl3, 400 MHz) δ: 1.44 (s, 3H, CH3), 4.48 (q, J = 7.1 Hz, 2H, CH2), 7.80-7.85 (m, 2H, Ar-H), 7.93-7.99 (m, 2H, Ar-H). Mass spectrum (ESI): m/z 220.1 [M + H]+.
storage
No special handling conditions or precautions are required.
Purification Methods
Crystallise the imide from toluene/pet ether (or *benzene/pet ether). It is partly soluble in Et2O, *benzene and CHCl3. [Heller & Jacobsohn Chem Ber 54 1112 1921, Beilstein 21/10 V 428.]
References
[1] Journal of Organic Chemistry, 1980, vol. 45, # 1, p. 174 - 175
[2] Organic Letters, 2015, vol. 17, # 23, p. 5846 - 5849
[3] Synthetic Communications, 1980, vol. 10, # 8, p. 611 - 614
[4] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 11, p. 2576 - 2588
[5] Patent: CN105732683, 2016, A. Location in patent: Paragraph 0090; 0091; 0092; 0093
