With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.59878-57-8,1-(Cyclopropylcarbonyl)piperazine,as a common compound, the synthetic route is as follows.
59878-57-8, To a round bottom flask containing Methyl-5-((4-oxo-3-((2-(trimethylsilyl)ethoxy) methyl)- 3,4-dihydrophthalazin-l-yl) methyl)-2-(4,4,5,5-tetramethyl-l,3,2-dioxa borolan-2- yl)benzoate and bis(pinacolato) diboron (2.00 g) was added THF (100 mL) before cooling to 0C. Upon cooling, 2M lithium hydroxide (7 mL, 14 mmol) was added dropwise before allowing to reaction to stir for 30 minutes at 0C. 1M HC1 was then added dropwise to the reaction mixture at 0C until reaching pH 4. The mixture was then extracted with EtOAc (3 x 80 mL) and washed with Brine (3 x 50 mL). The organic phases were combined and the excess solvent removed in vacuo. The crude material (1.4 g) was transferred to a round bottom flask upon which DCM (100 mL), HBTU (2.97 g, 7.84 mmol) and DIPEA (1.36 mL, 7.84 mmol) was added. After stirring at room temperature for 30 minutes, N- cyclopropylcarbonylpiperazine (1.11 mL, 7.85 mmol) was added and the reaction stirred overnight. After stirring for 16 hours, the excess solvent was removed in vacuo and the crude material isolated by flash column chromatography (Pure EtOAc) before purification by reverse phase HPLC was carried out to afford 4-(3-(4-(cyclopropanecarbonyl) piperazine- 1- carbonyl)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl)-2-((2-trimethlsilyl) ethoxy)methyl)phthalazin-l(2/7)-one (419 mg, 0.62 mmol, 22% – three steps) as a white solid in a mixture of rotamers. In each case the shift relating to the minor rotamer has been donated with an asterisk.* *H NMR (400 MHz, CDCb) d = 8.46 (dd, J = 7.8, 1.6 Hz, 1H + 1H*), 7.79 – 7.55 (m, 4H + 4H*), 7.32 – 7.28 (m, 1H + 1H*), 7.14 (bs, 1H + 1H*), 5.59 (s, 2H + 2H*), 4.33 (s, 2H + 2H*), 3.87 – 3.04 (m, 10H + 10H*), 1.28 (s, 12H + 12H*), 1.04 – 0.97 (m, 4H + 4H*), 0.90 – 0.85 (m, 1H + 1H*), 0.83 – 0.71 (m, 2H + 2H*), 0.00 (s, 9H + 9H*); 13C NMR (100 MHz, CDCb) d = 172.3 (1C + 1C*), 171.0 (1C + 1C*), 160.0 (1C + 1C*), 144.7 (1C + 1C*), 142.9 (1C + 1C*), 141.3 (1C + 1C*), 136.3 (1C + 1C*), 133.3 (1C + 1C*), 131.5 (1C + 1C*), 129.2 (1C + 1C*), 128.4 (1C + 1C*), 128.2 (1C + 1C*), 127.7 (1C + 1C*), 125.4 (1C + 1C*), 125.2 (1C + 1C*), 84.1 (2C + 2C*), 79.0 (1C + 1C*), 67.3 (1C + 1C*), 47.3 (1C*), 46.9 (1C), 45.2 (1C*), 44.8 (1C), 41.9 (1C*), 41.7 (2C), 41.4 (1C*), 39.1 (1C + 1C*), 24.9 (4C + 4C*), 18.1 (1C + 1C*), 11.1 (1C + 1C*), 7.66 (2C + 2C*), -1.36 (3C + 3C*) (the carbon bearing the boron substituent is not observed); IR (v, cm 1): 2981, 2889, 2360, 2341, 1641, 1382, 1354, 1146, 1087, 956; HRMS (ESI) for C36H49N4O610B23Na28Si [M+Na]+ requires 694.34429 found 694.34418; Mp: 78 – 80C.
59878-57-8 1-(Cyclopropylcarbonyl)piperazine 2064235, apiperazines compound, is more and more widely used in various fields.
Reference£º
Patent; OXFORD UNIVERSITY INNOVATION LIMITED; GOUVERNEUR, Veronique; CORNELISSEN, Bart; WILSON, Thomas Charles; (152 pag.)WO2019/186135; (2019); A1;,
Piperazine – Wikipedia
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