Synthesis of Pacritinib Hydrochloride

HAN Chang1, GUO Yajun1, PENG Jiajuan2, ZHU Xueyan1, SHAN Hanbin1*

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主办：上海医药工业研究院
　　　中国药学会
　　　中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
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Chinese Journal of Pharmaceuticals
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Chinese Journal of Pharmaceuticals ›› 2015, Vol. 46 ›› Issue (12) : 1269-1273. DOI: 10.16522/j.cnki.cjph.2015.12.001

Synthesis of Pacritinib Hydrochloride

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Abstract

Pacritinib hydrochloride was synthesized from 2-hydroxy-5-nitrobenzaldehyde by nucleophilic substitution with 1-(2-chloroethyl)pyrrolidine hydrochloride to give 5-nitro-2-[2-(pyrrolidin-1-yl)ethoxy]benzaldehyde, then followed by reduction, substitution, reduction and salification to obtain 3-[(allyloxy)methyl]-4-[2-(pyrrolidin-1- yl)ethoxy]aniline ditoluenesulfonate, which was subjected to condensation with 4-[3-[(allyloxy)methyl]phenyl]-2- chloropyrimidine, and olefin metathesis with an overall yield of about 13％(based on 2-hydroxy-5-nitrobenzaldehyde).

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myelofibrosis / pacritinib / synthesis / olefin metathesis

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HAN Chang1, GUO Yajun1, PENG Jiajuan2, ZHU Xueyan1, SHAN Hanbin1*. Synthesis of Pacritinib Hydrochloride. Chinese Journal of Pharmaceuticals. 2015, 46(12): 1269-1273 https://doi.org/10.16522/j.cnki.cjph.2015.12.001

References

[1] 潘 崚. 原发性骨髓纤维化发病机制研究进展[ J] . 白血病· 淋巴瘤, 2009, 18(10): 638-640.

[2] 吴 文. 原发性骨髓纤维化的诊治进展[J]. 中华临床医师杂志, 2013, 7(5): 25-28.

[3] Hart S, Goh KC, Novotny-Diermayr V, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies [J]. Leukemia, 2011, 25(11): 1751-1759.

[4] 魏春华, 杨彦彪, 张志叶. 首个骨髓纤维化的口服治疗药Ruxolitinib [J]. 甘肃科技, 2012, 28(24): 129-131.

[5] Hart S, Goh KC, Novotny-Diermayr V, et al. Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia [J]. Blood Cancer J, 2011, 1(11): e44.

[6] Derenzini E, Younes A. Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib [J]. Expert Opin Inv Drug, 2013, 22(6): 775-785.

[7] William AD, Lee AC, Blanchard S, et al. Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa- 5,7,26-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-125,226,3,5, 8,10,1227,16,21,23-decaene(SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3(JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma [J]. J Med Chem, 2011, 54(13): 4638-4658.

[8] William AD, Lee AC, Goh KC, et al. Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa- 5,7,14,26-traazatetracyclo [19.3.1.12,6.18,12]heptacosa-125,226,3,5,827,9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2(JAK2), and Fms-like tyrosine kinase-3(FLT3)

for the treatment of cancer [J]. J Med Chem, 2011, 55(1): 169-196.

[9] 史蒂芬妮· 班尼乔, 哈瑞许· 库玛· 密索· 那卡伽, 迈克尔· 安克森, 等. 氧连接的嘧啶衍生物: 中国, 101360751[P]. 2009-02-04.

[10] Chen DZ. Indole sustituted pyrimidines and use thereof in the treatment of cancer: WO, 2008060248 [P]. 2008-05-22.

[11] Penning TD, Chandrakumar NS, Chen BB, et al. Structureactivity relationship studies on 1-[2-(4-phenylphenoxy)- ethyl] pyrrolidine( SC-22716) , a potent inhibitor of leukotriene A4 (LTA4) hydrolase [J]. J Med Chem, 2000, 43(4): 721-735.

[12] Gandhi A, Dimartino J, Chopra R. Methods for the treatment of locally advanced breast cancer: WO, 2014039960 [P]. 2014-03-13.

[13] 迪莫克B, 李静霞, 威廉AD. 11-(2- 吡咯烷-1- 基- 乙氧基)-14,19- 二氧杂-5,7,26- 三氮杂- 四环[19.3.1.12,6.18,12]-二十七碳-125,226,3,5,8,10,1227,16,21,23- 十烯柠檬酸盐: 中国, 102282148 [P]. 2011-12-14.
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