5-(2,6-Dichloro-5-fluoro-3-pyridinyl)-3-phenyl-2-(trifluoromethyl)-pyrazolo[1,5-a]pyrimidin-7(4H)-one synthesis

Yield:1259536-62-3 80%

Reaction Conditions:

with acetic acid at 125; for 4 h;

Steps:

4.1.4. General procedures of parallel synthesis of PPOs compounds

General procedure: 4.1.4.1. 5-(2,6-Dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one (17)A solution of intermediate 5a (0.227 g, 1 mmol) and ethyl 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropanoate (0.28 g, 1 mmol) in acetic acid (8 ml) was added to a teat glass (40 ml) of Syncore Reactor, keeping the temperature at 125 °C and the rotational speed of the device at 300 rpm for 4 h. After this period, the solvent of reaction was concentrated to half under reduced pressure by Syncore Polyvap, and cooled to about 15 °C gradually. The mixture was filtered and the solid was washed with acetic acid and water to pH 7, to obtain the compound 17 (0.35 g, Yield: 80%, Purity: 98% by HPLC-DAD) as a white floccular solid. mp >300 °C; ESI-Ms (m/z): 443.2 [M + H]⁺; ¹H NMR (500 MHz, DMSO-d6) δ: 7.52 (m, 3H, Ph-H), 7.47 (m, 2H, Ph-H), 6.17 (s, 1H, 6-CH), 8.41 (d, 1H, J = 8, pyridine 4-CH), 12.90 (brs, 1H, NH); ¹³C NMR (125 MHz, DMSO-d6) δ: 99.33 (6-CH), 104.56 (3-C), 155.63 (7-CO), 152.57, 154.63 (5-C), 140.75 (2-C), 130.65 (Ph-C), 129.22 (Ph-C), 128.89 (Ph-C), 127.94 (Ph-C), 122.86 (CF₃), 146.91 (pyridine-C), 142.59 (pyridine-C), 137.94 (pyridine-C), 130.44 (pyridine-C), 130.26 (pyridine-C); HRMS (ESI) calcd for C₁₈H₉C_l2F₄N₄O ([M + H]⁺), 443.0090; found 443.0085; IRv_max (KBr):1701 (CO), 1629, 1558, cm^-1.

References:

Qi, Jinlong;Zhang, Fan;Mi, Yi;Fu, Yan;Xu, Wen;Zhang, Diqun;Wu, Yibing;Du, Xiaona;Jia, Qingzhong;Wang, Kewei;Zhang, Hailin [European Journal of Medicinal Chemistry,2011,vol. 46,# 3,p. 934 - 943] Location in patent:experimental part