With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.204512-95-8,(S)-Tetrahydrofuran-3-amine hydrochloride,as a common compound, the synthetic route is as follows.
Example 51 N-[(2r,5s)-5-hydroxyadamantan-2-yl] 4-cyclopropyl-2-[(3S)-oxolan-3-yl]amino]pyrimidine-5-carboxamide 4-cyclopropyl-N-[(2r,5s)-5-hydroxyadamantan-2-yl]-2-methylsulfonylpyrimidine-5-carboxamide (Intermediate 80, 0.3 g, 0.77 mmol), (S)-tetrahydrofuran-3-amine hydrochloride (0.189 g, 1.53 mmol) and DIPEA (0.294 mL, 1.69 mmol) were dissolved in THF (5 mL) and sealed into a microwave tube. The reaction was heated to 150 C. for 1 hour in the microwave reactor and cooled to room temperature. The reaction mixture was diluted with DCM (20 ml) and washed with saturated NaHCO3, then separated through a phase sep tube and the DCM layer evaporated. Purified by preparative HPLC (Phenomenex Gemini C18 110A (axia) column, 5mu silica, 30 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.5% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the product, 4-cyclopropyl-N-[(2r,5s)-5-hydroxyadamantan-2-yl]-2-[[(3S)-oxolan-3-yl]amino]pyrimidine-5-carboxamide (0.106 g, 35%). Chiral analysis was carried out using 5 mum Chiralcel OJ-H (250 mm*4.6 mm)-No DG022, eluding with iso-Hexane/EtOH 80/20. The compound appears to have a chiral purity >98%. 1H NMR (400.132 MHz, CDCl3) delta 1.00-1.03 (2H, m), 1.17-1.23 (2H, m), 1.55 (2H, d), 1.69-1.87 (8H, m), 1.94 (2H, d), 2.17 (1H, s), 2.24-2.34 (3H, m), 2.45-2.52 (1H, m), 3.67 (1H, dd), 3.81-3.87 (1H, m), 3.92-3.99 (2H, m), 4.18-4.23 (1H, m), 4.52 (1H, s), 5.32 (1H, d), 6.03 (1H, d), 8.32 (1H, s) m/z (ES+) (M+H)+=399; HPLC tR=1.50 min., 204512-95-8
As the paragraph descriping shows that 204512-95-8 is playing an increasingly important role.
Reference£º
Patent; AstraZeneca AB; US2009/264401; (2009); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem