CN110615744B - 一种布瓦西坦中间体及其制备方法 - Google Patents
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Abstract
本发明提出一种化合物,3‑((((S)‑1‑氨基‑1‑氧代丁‑2‑基)氨基)甲基)己酸(I),以及其制备方法。该化合物(I)包含(R)‑3‑((((S)‑1‑氨基‑1‑氧代丁‑2‑基)氨基)甲基)己酸(I)‑R,或(S)‑3‑((((S)‑1‑氨基‑1‑氧代丁‑2‑基)氨基)甲基)己酸(I)‑S,或者任意比例的(I)‑R与(I)‑S的混合物。本发明式(I)的化合物,可以用于布瓦西坦的合成,为设计简洁高效的路线合成布瓦西坦提供了新的思路和方法。
Description
技术领域
本发明涉及布瓦西坦合成技术领域,更具体地,涉及中间体3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I),以及其合成技术领域。
背景技术
布瓦西坦(Brivaracetam)是UCB公司开发的新一代抗癫痫药物,2016年2月,美国FDA批准布瓦西坦上市,布瓦西坦可以作为其他药物的附加药物治疗部分发作性癫痫。
布瓦西坦(S)-2-((R)-2-氧代-4-丙基吡咯啉-1-基)丁酰胺的结构如式1所示,本发明设计了一种新的化合物3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I),该化合物(I)包含(R)-3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)-R,或(S)-3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)-S,或者任意比例的(I)-R与(I)-S的混合物。其中异构体(R)-3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)-R可以通过关环反应得到布瓦西坦。
由于布瓦西坦分子中有两个手性中心,对应四个不同的异构体,这给布瓦西坦的合成带来了一定的难度。目前合成布瓦西坦的方法主要有以下报道:
最早的方法是UCB开发的,以正戊醛为原料,先与乙醛酸环合,再与L-氨基丁酰胺反应,得到的产物氢化,生成一对非对映异构体,再通过柱层析分离纯化得到产物布瓦西坦(式2),如专利CN1208319C、CN1882535B所述。该方法步骤虽短,但最后一步只能柱层析分离,成本高而且不适合大量生产,限制了其应用。
CN107663185A报道了以(R)-4-丙基二氢呋喃-2(3H)-酮为中间体与L-氨基丁酰胺反应得到布瓦西坦(式3)。但是手性的(R)-4-丙基二氢呋喃-2(3H)-酮合成路线很长,涉及到金属试剂反应,而且它与L-氨基丁酰胺也需要多步转化才能得到目标产物。这使整个合成方案路线长,操作繁琐。
CN106748950A报道了以差向异构体混合物酸为中间体,通过与R-苯乙胺的成盐纯化的方法得到单一异构体酸,再转化成布瓦西坦的方法(式4)。该方法相对比较简洁,实用性较强。
发明内容
为了探索简洁高效的合成布瓦西坦的方法,本发明提出了一种中间体3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)。
该化合物(I)包含(R)-3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)-R,或(S)-3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)-S,或者任意比例的(I)-R与(I)-S的混合物。
本发明还提出一种合成中间体3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)的方法,该方法以(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)为原料,在水中氢化还原,得到式(I)的化合物。
较佳的,所述的氢化还原的催化剂为钯碳,反应温度为10~50oC,压力1~30bar。
本发明还涉及一种合成中间体(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)的方法,该方法以正戊醛与乙醛酸为原料,先按CN1208319C和CN1882535B中的方法合成中间体5-羟基-4-丙基呋喃-2(5H)-酮(III),中间体(III)与L-氨基丁酰胺在醇溶剂体系中反应得到中间体(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)。
较佳的,所述的醇溶剂为异丙醇,反应温度为30~40oC,反应时间2~4小时。
具体实施方式
为更好的理解本发明的内容,下面结合具体实施例作进一步说明。应理解,下列具体实施例仅仅用于说明本发明,而不是对本发明的限制。
实施例1:5-羟基-4-丙基呋喃-2(5H)-酮(III)的制备
将正庚烷125mL和吗啡啉30mL加入三口瓶中,常温下搅拌10min混合均匀,降温至4oC以下滴加50%乙醛酸水溶液25.0g。滴完后升温至25~30oC搅拌反应2h,然后在40oC以下缓慢加入正戊醛30.5g,继续搅拌反应18h。反应完成后降温至20oC,缓慢滴加浓盐酸21.3g搅拌。
降至室温,静置分去正庚烷相。水相中加入乙酸乙酯100mL,缓慢加入碳酸钠固体调pH=4,分层取有机相,再用乙酸乙酯萃取,合并的有机相用饱和食盐水洗涤,无水硫酸钠干燥、抽滤、减压浓缩,得棕色油状物5-羟基-4-丙基呋喃-2(5H)-酮(III) 43.9g,收率91.5%。1H NMR (400 MHz, Chloroform-d) δ 0.93-1.00 (t, 3H), 1.56-1.67 (q, 2H),2.31-2.43 (q, 2H), 5.81 (s, 1 H), 6.02 (s, 1 H). MS (ESI) m/z =143 (M++1)。
实施例2:(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)的制备
将氨基丁酰胺盐酸盐96.2g混溶于异丙醇1000mL中,通氨气进行游离,直至体系pH值为9~10,且pH值不变化为止。过滤除去盐,滤液浓缩至500mL待用。
将5-羟基-4-丙基呋喃-2(5H)-酮(III) 98.4g分批加入上述500mL氨基丁酰胺溶液中,控温30~40oC反应2h以上。反应完成后过滤去除盐,滤液缓慢降温至0~5oC析晶,抽滤,用少量乙酸乙酯漂洗,得白色固体(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)139.2g,收率88.8%。1H NMR (500 MHz, Chloroform-d) δ 6.45 (s, 1H),5.89 (s, 1H), 5.85 (s, 1H), 5.57 (s, 1H), 3.42 (s, 1H), 2.39 (s, 3H), 1.82(dq, J = 14.4, 7.4, 6.9 Hz, 1H), 1.74 (dt, J = 14.2, 7.2 Hz, 1H), 1.67 (dd, J= 14.6, 7.2 Hz, 2H), 1.02 (dt, J = 11.3, 7.4 Hz, 6H). MS (ESI) m/z =227 (M++1)。
实施例3:3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)的制备
将(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II) 15.0g加入到150mL水中,再加入5%的Pd/C 1.5g, 搅拌均匀,氮气置换。通氢气至20bar,常温搅拌反应过夜。反应完后,过滤去钯碳,旋干滤液得到淡黄色油状物3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)16.3g,收率93.7%。1H NMR (400 MHz, DMSO-d 6) δ 7.34 (s,1H), 7.01 (s, 1H), 2.96 – 2.79 (m, 1H), 2.56 (dd, J = 11.6, 4.9 Hz, 1H), 2.40(d, J = 4.8 Hz, 1H), 2.29 (ddt, J = 28.6, 20.1, 10.3 Hz, 1H), 2.13 (ddd, J =21.1, 11.9, 5.2 Hz, 1H), 1.93 – 1.74 (m, 1H), 1.49 (tt, J = 13.6, 6.5 Hz,2H), 1.41 – 1.07 (m, 4H), 0.82 (dt, J = 29.2, 6.6 Hz, 6H). MS (ESI) m/z =231(M++1)。
在此说明书中,本发明已参照其特定的实施例作了描述。但是,很显然仍可以作出各种修改和变换而不背离本发明的精神和范围。因此,说明书应被认为是说明性的而非限制性的。
Claims (1)
1.一种制备化合物3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)的方法,该化合物有如下结构;
所述的一种制备化合物3-((((S)-1-氨基-1-氧代丁-2-基)氨基)甲基)己酸(I)的方法,包括将(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)在水中氢化还原,得到式(I)的化合物;
所述氢化还原方法的催化剂为钯碳,反应温度为10~50℃,压力20~30bar;
所述的(2S)-2-(2-羟基-5-氧代-3-丙基-2,5-二氢-1H-吡咯-1-基)丁酰胺(II)的制备方法,包括将5-羟基-4-丙基呋喃-2(5H)-酮(III)与L-氨基丁酰胺在醇类溶剂中反应得到式(II)的化合物;
所述的醇类溶剂为异丙醇,反应温度为30~40℃,反应时间2~4小时。
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US16/973,022 US11518741B2 (en) | 2018-06-20 | 2018-10-30 | Brivaracetam intermediate, preparation method therefor, and preparation method for brivaracetam |
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CN110615744B (zh) | 2018-06-20 | 2023-01-06 | 上海朴颐化学科技有限公司 | 一种布瓦西坦中间体及其制备方法 |
CN112341413A (zh) * | 2019-12-18 | 2021-02-09 | 上海朴颐化学科技有限公司 | 一种用于合成布瓦西坦的中间体及其制备方法 |
CN111187175A (zh) * | 2020-01-08 | 2020-05-22 | 上海朴颐化学科技有限公司 | 一种利用微通道反应器氢化制备布瓦西坦的中间体的方法 |
CN113651745B (zh) * | 2021-09-09 | 2023-06-02 | 上海医药工业研究院 | 布瓦西坦中间体及其制备方法和纯化方法 |
CN114634437B (zh) * | 2022-03-29 | 2023-05-30 | 武汉氟本氘合新材料科技有限公司 | 一种布瓦西坦的简易制备方法 |
CN116891879A (zh) * | 2023-09-08 | 2023-10-17 | 山东静远药业有限公司 | 一种布瓦西坦关键中间体的合成方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1882535A (zh) * | 2003-09-24 | 2006-12-20 | Ucb股份有限公司 | 2-氧代-1-吡咯烷衍生物的制备方法 |
CN106279074A (zh) * | 2015-05-25 | 2017-01-04 | 苏州鹏旭医药科技有限公司 | 一种化合物及其制备方法和在合成布瓦西坦中的用途 |
TW201730151A (zh) * | 2016-02-24 | 2017-09-01 | Suzhou Pengxu Pharmatech Co Ltd | 布瓦西坦(Brivaracetam)之製備方法 |
CN109593055A (zh) * | 2017-09-30 | 2019-04-09 | 上海医药工业研究院 | 一种布瓦西坦异构体(2s,4s)的制备方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1206699B (it) * | 1984-02-27 | 1989-04-27 | Isf Spa | Procedimento per preparare derivati di pirrolidone. |
GB0004297D0 (en) | 2000-02-23 | 2000-04-12 | Ucb Sa | 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses |
AU2002224847A1 (en) * | 2000-11-21 | 2002-06-03 | U C B, S.A. | N-alkylated gaba compounds, processes for their preparation and their use as medicaments |
WO2008132142A2 (en) | 2007-04-27 | 2008-11-06 | Ucb Pharma S.A. | New heterocyclic derivatives useful for the treatment of cns disorders |
WO2011086565A1 (en) * | 2010-01-15 | 2011-07-21 | Lupin Limited | Method for preparation of enantiomerically enriched and/or racemic gamma-amino acids |
JP6872500B2 (ja) | 2015-05-25 | 2021-05-19 | エステベ・キミカ・ソシエダッド・アノニマEsteve Quimica, S.A. | ブリバラセタムを製造する方法 |
RU2629117C1 (ru) * | 2016-06-14 | 2017-08-24 | Сизов Владимир Владимирович | Способ получения 4-замещенного 2-[2-оксо-1-пирролидинил] ацетамида |
CN106748950B (zh) * | 2017-01-13 | 2019-09-03 | 成都美域高制药有限公司 | 一种布瓦西坦及其中间体的制备方法 |
WO2018220646A1 (en) | 2017-05-29 | 2018-12-06 | Msn Laboratories Private Limited, R&D Center | An improved process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyltetrahydro-1h-pyrrol-1-yl] butanamide and its intermediates thereof |
CN107513032A (zh) | 2017-07-25 | 2017-12-26 | 峨眉山宏昇药业股份有限公司 | 一种用于治疗癫痫的药物及其中间体的合成方法 |
CN107663185A (zh) | 2017-11-14 | 2018-02-06 | 安徽华胜医药科技有限公司 | 一种丁内酯衍生物的合成方法 |
CN110615744B (zh) | 2018-06-20 | 2023-01-06 | 上海朴颐化学科技有限公司 | 一种布瓦西坦中间体及其制备方法 |
-
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1882535A (zh) * | 2003-09-24 | 2006-12-20 | Ucb股份有限公司 | 2-氧代-1-吡咯烷衍生物的制备方法 |
CN106279074A (zh) * | 2015-05-25 | 2017-01-04 | 苏州鹏旭医药科技有限公司 | 一种化合物及其制备方法和在合成布瓦西坦中的用途 |
TW201730151A (zh) * | 2016-02-24 | 2017-09-01 | Suzhou Pengxu Pharmatech Co Ltd | 布瓦西坦(Brivaracetam)之製備方法 |
CN109593055A (zh) * | 2017-09-30 | 2019-04-09 | 上海医药工业研究院 | 一种布瓦西坦异构体(2s,4s)的制备方法 |
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CN110615744A (zh) | 2019-12-27 |
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JP2021527703A (ja) | 2021-10-14 |
EP3812377A4 (en) | 2022-03-16 |
US11518741B2 (en) | 2022-12-06 |
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EP3812377A1 (en) | 2021-04-28 |
CN112020498A (zh) | 2020-12-01 |
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