With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.249889-68-7,8-Chloro-2-methoxy-1,5-naphthyridine,as a common compound, the synthetic route is as follows.
A mixture of 8-chloro-2-methoxy-l,5-naphthyridine (31.83 mg, 163.56 umol, 2.00 eq), 6-[4-(4-methylpiperazin-l-yl)-l-piperidyl]-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyrazolo[l,5-a]pyrimidine (74.19 mg, 81.78 umol, 1.00 eq), Pd(dppf)Cl2 (11.97 mg, 16.36 umol, 0.20 eq), K2CO3 (33.91 mg, 245.34 umol, 3.00 eq) in dioxane/H20 (6.00 mL/0.9 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 120C for 1 hour under N2 atmosphere until LCMS showed the starting material was consumed completely. The reaction mixture was concentrated in vacuo to give a residue, which was purified by Biotage flash reversed-phase C-18 column chromatography eluting with MeOH/H20 (MeOH in water from 10% to 100%) to give the product of 2-methoxy-8-[6-[4-(4-methylpiperazin-l- yl)-l-piperidyl]pyrazolo[l,5-a]pyrimidin-3-yl]-l,5-naphthyridine (60) as a yellow solid. LC/MS (method 3): fe = 2.22 min, mlz (M + H)+ = 459.2; NMR (400 MHz, MeOD) delta 9.50 (s, 1H), 8.88 (d, J= 5.2 Hz, 1H), 8.77 (d, J= 2.4 Hz, 1H), 8.67 (d, J = 4.8 Hz, 1H), 8.41 (d, J = 2.8 Hz, 1H), 8.19 (d, J = 9.2 Hz, 1H), 7.24 (d, J = 9.2 Hz, 1H), 4.15 (s, 3H), 3.77-3.74 (m, 2H), 2.82-2.40 (m, 11H), 2.30 (s, 3H), 2.10-2.07 (m, 2H), 1.80-1.69 (m, 2H).
249889-68-7, The synthetic route of 249889-68-7 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; THE BRIGHAM AND WOMEN’S HOSPITAL, INC.; THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES; YU, Paul, B.; HUANG, Wenwei; SANDERSON, Philip, Edward; JIANG, Jian-kang; SHAMIM, Khalida; ZHENG, Wei; HUANG, Xiuli; TAWA, Gregory; LEE, Arthur; ALIMARDANOV, Asaf; HUANG, Junfeng; (357 pag.)WO2018/200855; (2018); A1;,
1,8-Naphthyridine – Wikipedia
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