23491-48-7 5-(4-甲基哌嗪)-2-硝基苯胺

运输方式为冰袋运输。危险等级为IRRITANT（刺激性），海关编码29335990，非危险化学品。

化学合成

化学合成

合成路线 1（原料：5-氟-2-硝基苯胺）

• 步骤：将5-氟-2-硝基苯胺（1g）、1-甲基哌嗪（0.752ml）和三乙胺（1.86ml）在N-甲基吡咯烷酮（1.5ml）中混合，置于微波反应器中，于100℃加热反应20小时。反应完成后冷却至室温，加入去离子水（50ml）稀释，搅拌20分钟后过滤，黄色固体用去离子水洗涤，高真空干燥得目标产物。
• 条件：微波辐射；100℃；20小时；溶剂为N-甲基吡咯烷酮（NMP）；碱为三乙胺（TEA）
• 收率：1.45g
• 参考文献：[1] Journal of Medicinal Chemistry, 2009, vol. 52, #2, p.278-292；[2] Journal of Medicinal Chemistry, 2016, vol.59, #14, p.6690-6708；[3] Patent: US2004/122237, 2004, A1 (Page 247-248)；[4] Patent: WO2004/18419, 2004, A2 (Page 260)；[5] Patent: US2010/81653, 2010, A1 (Page/Page column 12)；[6] Bioorganic and Medicinal Chemistry Letters, 2011, vol.21, #24, p.7325-7330；[7] Patent: WO2013/114332, 2013, A1 (Page/Page column 123)；[8] Patent: US2014/371204, 2014, A1 (Paragraph 0867)

合成路线 2（原料：2-硝基-5-氯苯胺）

• 步骤：将2-硝基-5-氯苯胺（3.4g，19.77mmol）、1-甲基哌嗪（4.4ml，52mmol）、无水碳酸钾（K₂CO₃）和无水N,N-二甲基甲酰胺（DMF，41ml）混合，用CaCl₂干燥管保护，120℃加热反应20小时。冷却后倒入300ml冰冷水中，过滤得黄色固体，用四氯化碳（CCl₄）重结晶得目标产物。
• 条件：120℃；20小时；溶剂为N,N-二甲基甲酰胺（DMF）；碱为碳酸钾（K₂CO₃）；保护装置为CaCl₂干燥管
• 收率：4.237g（100%）
• 表征：熔点152℃；IR；¹H NMR（δ: 7.27(s,3H,NCH₃), 2.47(m,4H,H₃',5'), 6.0(d,J=3Hz,1H,H6), 6.37(dd,J=10,3Hz,1H,H4), 6.89(s,2H,NH₂)）
• 参考文献：[1] Patent: WO2004/63170, 2004, A1 (Page 7)；[2] Chimia, 2006, vol.60, #9, p.584-592；[3] Patent: WO2008/112509, 2008, A1 (Page/Page column 28-29)；[4] Patent: WO2006/81445, 2006, A2 (Page/Page column 37-38)；[5] Patent: WO2006/127926, 2006, A2 (Page/Page column 63)；[6] Patent: WO2005/82340, 2005, A2 (Page/Page column 95)；[7] Patent: WO2014/141015, 2014, A1 (Page/Page column 32-34)；[8] Patent: WO2008/112509, 2008, A1 (Page/Page column 27-28)；[9] Patent: US2008/293738, 2008, A1 (Page/Page column 10; 12-13)；[10] Patent: WO2005/82340, 2005, A2 (Page/Page column 95)；[11] Patent: WO2006/81445, 2006, A2 (Page/Page column 36)；[12] Patent: WO2006/125130, 2006, A1 (Page/Page column 57-58)；[13] Patent: WO2006/125130, 2006, A1 (Page/Page column 59-60)；[14] Patent: WO2006/127926, 2006, A2 (Page/Page column 63)；[15] Patent: WO2005/82340, 2005, A2 (Page/Page column 94)；[16] Patent: WO2006/124413, 2006, A2 (Page/Page column 52-54)；[17] Patent: WO2008/112509, 2008, A1 (Page/Page column 27)；[18] Patent: US2008/293738, 2008, A1 (Page/Page column 12)；[19] Patent: WO2005/82340, 2005, A2 (Page/Page column 94)；[20] Patent: WO2006/125130, 2006, A1 (Page/Page column 60-62)；[21] Patent: WO2006/125130, 2006, A1 (Page/Page column 61)；[22] Patent: WO2006/125130, 2006, A1 (Page/Page column 55; 58-59; 62-63)；[23] Patent: CN108610293, 2018, A (Paragraph 0032-0038; 0048-0049; 0052-0053; 0056-0057)；[24] Patent: WO2006/125130, 2006, A1 (Page/Page column 61-62; 64)；[25] Journal of Organic Chemistry USSR (English Translation), 1987, vol.23, p.576-580；[26] Zhurnal Organicheskoi Khimii, 1987, vol.23, #3, p.637-642；[27] Journal of Medicinal Chemistry, 2014, vol.57, #16, p.6973-6988；[28] Journal of Medicinal Chemistry, 2010, vol.53, #3, p.1357-1369；[29] Organic and Biomolecular Chemistry, 2015, vol.13, #30, p.8335-8348；[30] European Journal of Medicinal Chemistry, 2011, vol.46, #2, p.659-669；[31] Bioorganic and Medicinal Chemistry Letters, 2001, vol.11, #21, p.2905-2919；[32] Patent: WO2007/45096, 2007, A1 (Page/Page column 39; 72; 74)；[33] Patent: WO2009/110000, 2009, A1 (Page/Page column 10)；[34] Pharmazie, 1989, vol.44, #9, p.606-607；[35] Letters in Drug Design and Discovery, 2015, vol.12, #5, p.374-384；[36] Journal of Medicinal Chemistry, 1996, vol.39, #4, p.992-998；[37] Bioorganic and Medicinal Chemistry, 2016, vol.24, #16, p.3680-3686；[38] Bioorganic and Medicinal Chemistry, 2006, vol.14, #13, p.4490-4518；[39] Journal of Medicinal Chemistry, 2014, vol.57, #15, p.6642-6652；[40] Australian Journal of Chemistry, 1994, vol.47, #2, p.247-262；[41] Bioorganic and Medicinal Chemistry Letters, 2013, vol.23, #20, p.5689-5693；[42] Patent: US9072761, 2015, B2 (Page/Page column 81; 82; 95; 96; 101)；[43] Bioorganic and Medicinal Chemistry Letters, 2012, vol.22, #5, p.1949-1952；[44] Bioorganic and Medicinal Chemistry Letters, 2004, vol.14, #18, p.4791-4794；[45] Patent: US2005/261307, 2005, A1；[46] Patent: WO2004/18419, 2004, A2 (Page 260)；[47] Journal of Medicinal Chemistry, 2012, vol.55, #17, p.7460-7471；[48] RSC Advances, 2015, vol.5, #93, p.75911-75917；[49] Chemical Communications, 2015, vol.51, #80, p.14885-14888；[50] Patent: WO2008/55959, 2008, A1 (Page/Page column 68)