With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.110256-15-0,5-Cyclopropylisoxazole-3-carboxylic acid,as a common compound, the synthetic route is as follows.
To a solution of cis tert-butyl 4-amino-2-methylpiperidine-1-carboxylate (1 g, 4.67 mmol) and DIPEA (2.44 ml, 14 mmol) in DMF (25ml) was added 5-cyclopropyl- 1,2-oxazole-3-carboxylic acid (0.86 g, 5.6 mmol) followed by HATU (2.31 g, 6.07 mmol). The reaction was stirred at rt. LCMS analysis after ~1h showed a trace of SM and mainly product (72%, 1.33min, MNa+.=371.95). The reaction was poured into water (100ml) and the product was extracted with EtOAc (3x50ml). The combined organic layers were washed with water (2x50ml), brine (50ml), dried over Na2SO4, filtered and concentrated. The red oily residue was purified by Isolera over SiO2 (100g), eluting with a gradient of EtOAc in heptane from 5 to 50 % to yield 1.55 g (95%) of the amide as an amber viscous. TLC (25% EtOAc in Hept), rf:0.30.1H NMR (500 MHz, Chloroform-d) 6.85 (d, J = 6.8 Hz, 1H), 6.31 (s, 1H), 4.21 (hept, J = 6.8, 6.1 Hz, 2H), 3.85 (ddd, J = 14.0, 5.5, 3.1 Hz, 1H), 3.13 (ddd, J = 14.3, 11.9, 3.9 Hz, 1H), 2.06 (ddd, J = 8.4, 4.9, 3.4 Hz, 1H), 2.02- 1.91 (m, 2H), 1.74- 1.66 (m, 2H), 1.45 (s, 9H), 1.25 (d, J = 7.2 Hz, 3H), 1.13- 1.08 (m, 2H), 1.00- 0.94 (m, 2H). LCMS analysis (METCR1673 Generic 2 minutes), 100%, 1.33min, [MNa]+.=372.00.
110256-15-0, As the paragraph descriping shows that 110256-15-0 is playing an increasingly important role.
Reference£º
Patent; EPIZYME, INC.; MITCHELL, Lorna Helen; BELL, Andrew Simon; CHESWORTH, Richard; FOLEY, Megan Alene Cloonan; KUNTZ, Kevin Wayne; MILLS, James Edward John; MUNCHHOF, Michael John; (375 pag.)WO2016/40515; (2016); A1;,
Isoxazole – Wikipedia
Isoxazole | C3H3NO – PubChem