化学合成，亮菌甲素的中间体。
医药
合成路线 1（1. 合成：3788-94-1）
产率：80%
合成条件：at 130℃; for 5 h;
实验步骤：2.22实施例22 {通过方案12制备）-6 - [（3-环丁基-2,3,4,5-四氢-1H-3-苯并吖庚因-7-基）甲基] -2-（3-甲氧基氮杂环丁烷-1-酮 y）-6,7-二氢-5H-吡咯并[3,4-d]嘧啶-5-酮。 步骤a）中间体2-（乙氧基亚甲基）-3-氧代丁酸乙酯将3-氧代丁酸乙酯（20g，154mmol），原甲酸三乙酯（51.1ml，307mmol）和乙酸酐（43.5ml，461mmol）的溶液加热 在130°C下保持5小时。 将反应冷却至室温。 减压浓缩除去原甲酸三乙酯和乙酸酐。 通过蒸馏（30毫巴，30-70℃）除去剩余的乙酸酐和原甲酸三乙酯。 蒸馏出2-（乙氧基亚甲基）-3-氧代丁酸乙酯（6毫巴，80℃至128℃），得到2-（乙氧基亚甲基）-3-氧代丁酸乙酯，为粘稠的黄色油状物（22.8g，80％）NMR（ 400MHz，CDCl 3）δ7.59-7.69（m，1H），4.17-4.34（m，4H），2.29-2.44（m，3H），1.25-1.44（m，6H）。
参考文献：
- [1] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 4, p. 946 - 950 [2] Mendeleev Communications, 2016, vol. 26, # 1, p. 54 - 56 [3] Patent: WO2011/83316, 2011, A1. Location in patent: Page/Page column 52-53 [4] Letters in Drug Design and Discovery, 2016, vol. 13, # 9, p. 912 - 920 [5] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3563 - 3567 [6] Patent: WO2013/109388, 2013, A2. Location in patent: Page/Page column 141 [7] Journal of medicinal chemistry, 2000, vol. 43, # 21, p. 3995 - 4004 [8] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 935 - 945 [9] Heterocycles, 2004, vol. 64, p. 177 - 191 [10] Journal of the American Chemical Society, 1952, vol. 74, p. 4889 [11] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1979, p. 464 - 471 [12] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 1875 - 1880 [13] Journal of Medicinal Chemistry, 1992, vol. 35, # 18, p. 3413 - 3422 [14] Journal of Medicinal Chemistry, 2005, vol. 48, # 4, p. 1229 - 1236 [15] Patent: US2005/96353, 2005, A1. Location in patent: Page/Page column 21 [16] Patent: US2006/30708, 2006, A1. Location in patent: Page/Page column 10-11 [17] Tetrahedron, 2013, vol. 69, # 40, p. 8564 - 8571 [18] Russian Journal of General Chemistry, 2013, vol. 83, # 7, p. 1330 - 1335 [19] Zh. Obshch. Khim., 2013, vol. 83, # 7, p. 1330 - 1335 [20] Russian Journal of Organic Chemistry, 2017, vol. 53, # 3, p. 381 - 392 [21] Zh. Org. Khim., 2017, vol. 53, # 3, p. 384 - 394,11 [22] Molecules, 2015, vol. 20, # 3, p. 4383 - 4394 [23] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4488 - 4510 [24] Patent: CN106212482, 2016, A. Location in patent: Paragraph 0031; 0032 [25] Patent: CN106135228, 2016, A. Location in patent: Paragraph 0027-0029 [26] Patent: CN106243101, 2016, A. Location in patent: Paragraph 0027; 0028
