醋酸艾司利卡西平 | 236395-14-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 醋酸艾司利卡西平
• 中文别名: (S)-(-)-10-乙酸基-10,11-二氢-5H-二苯[b,f]吖庚因-5-甲酰胺；艾司利卡西平醋酸盐；艾司利卡西平醋酸酯
• 英文名称: eslicarbazepine acetate
• 英文别名: (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide；(S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate；BIA 2-093；(-)-(S)-10-acetoxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide；(-)-Licarbazepine acetate；[(5S)-11-carbamoyl-5,6-dihydrobenzo[b][1]benzazepin-5-yl] acetate
• CAS: 236395-14-5
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: QIALRBLEEWJACW-INIZCTEOSA-N

物化性质

• 熔点：
  183-185°C
• 沸点：
  427.4±55.0 °C(Predicted)
• 密度：
  1.32
• 溶解度：
  不溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

醋酸艾司利卡唑是迅速且广泛地通过水解首过代谢转化为其主要活性代谢物艾司利卡唑。艾司利卡唑大约占系统暴露的92%。次要活性代谢物（R）-利卡唑和氧卡唑占系统暴露的不到5%。活性代谢物随后转化为无活性的葡萄糖苷酸，这些葡萄糖苷酸大约占系统暴露的3%。在研究人类肝脏微粒体时，艾司利卡唑对CYP2C19有中等抑制作用，并对UGT1A1介导的葡萄糖苷酸化有轻微激活作用。已经证明艾司利卡唑在体内可诱导CYP3A4酶。

Eslicarbazepine acetate is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, via hydrolytic first-pass metabolism. Eslicarbazepine corresponds to about 92% of systemic exposure. Minor active metabolites (R)-licarbazepine and oxcarbazepine consist of <5% of systemic exposure. Active metabolites are then metabolized to inactive glucuronides that correspond to about 3% of systemic exposure. Eslicarbazepine had a moderate inhibitory effect on CYP2C19 and a mild activation of UGT1A1-mediated glucuronidation when studied in human hepatic microsomes. It has been shown to induce CYP3A4 enzymes in vivo.

来源:DrugBank

毒理性

• 蛋白质结合

Eslicarbazepine与血浆蛋白的结合率相对较低，不超过40%，且与浓度无关。体外研究表明，华法林、地西泮、地高辛、苯妥英或妥拉唑林等药物的存在并不会显著影响Eslicarbazepine的血浆蛋白结合。同样，Eslicarbazepine的存在也不会显著影响这些药物的蛋白结合。

Eslicarbazepine is bound to plasma proteins at a relatively low rate of <40%, independent of concentration. In vitro studies have shown that plasma protein binding is not relevantly affected by the presence of other medications such as warfarin, diazepam, digoxin, phenytoin or tolbutamide. Similarly, the binding of these medications was not significantly affected by the presence of eslicarbazepine.

来源:DrugBank

吸收、分配和排泄

• 吸收

Eslicarbazepine的活性代谢产物具有很高的生物利用度，在给定剂量后1-4小时达到血清峰浓度。Eslicarbazepine醋酸盐的吸收不受食物影响。

Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.

来源:DrugBank

吸收、分配和排泄

• 消除途径

醋酸艾司利卡西平及其代谢物主要通过肾脏排泄。艾司利卡西平的活性代谢物有三分之二以原形排泄，三分之一以葡萄糖醛酸苷结合形式排泄。这大约占总排泄代谢物的90%，其余10%为少量代谢物。预计艾司利卡西平会在肾小管发生重吸收。

Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

根据群体药代动力学分析，70公斤体重的乙酰卡马唑的表观分布容积为61.3升。

The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.

来源:DrugBank

吸收、分配和排泄

• 清除

在肾功能正常的健康受试者中，艾司利卡巴嗪的肾清除率大约为20毫升/分钟。

Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.

来源:DrugBank

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  温度在0-10°C之间；请避免加热。

SDS

Eslicarbazepine Acetate
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: Eslicarbazepine Acetate
5.3

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
HEALTH HAZARDS
Specific target organ toxicity Narcotic effects
- Single exposure [Category 3]
ENVIRONMENTAL HAZARDS Not classified
GHS label elements, including precautionary statements
Pictograms or hazard symbols
Signal word Warning
Hazard statements
May cause drowsiness or dizziness
Precautionary statements:
Avoid breathing dust/fume/gas/mist/vapours/spray.
[Prevention]
Use only outdoors or in a well-ventilated area.
IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for
[Response]
breathing.
Call a POISON CENTER or doctor/physician if you feel unwell.
[Storage] Store in a well-ventilated place. Keep container tightly closed.
Store locked up.
[Disposal] Dispose of contents/container through a waste management company authorized by
the local government.

---

Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: Eslicarbazepine Acetate
Percent: >98.0%(HPLC)(N)
CAS Number: 236395-14-5
BIA 2-093 , (S)-(-)-10-Acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide
Synonyms:
Chemical Formula: C17H16N2O3
Eslicarbazepine Acetate

---

Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Call a POISON CENTER or doctor/physician if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Gently wash with plenty of
soap and water. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth.
A rescuer should wear personal protective equipment, such as rubber gloves and air-
Protection of first-aiders:
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
Special protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

---

Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, Use extra personal protective equipment (P3 filter respirator for toxic particles). Keep
protective equipment and people away from and upwind of spill/leak. Entry to non-involved personnel should
emergency procedures: be controlled around the leakage area by roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

---

Section 7. HANDLING AND STORAGE
Precautions for safe handling
Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment.
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a closed system if possible. Use a local exhaust if dust or aerosol will be
generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a refrigerator.
Store locked up.
Store away from incompatible materials such as oxidizing agents.
Heat-sensitive
Packaging material: Comply with laws.

---

Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Engineering controls: Install a closed system or local exhaust. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator, self-contained breathing apparatus(SCBA), supplied air respirator,
etc. Use respirators approved under appropriate government standards and follow
local and national regulations.
Hand protection: Impervious gloves.
Safety goggles. A face-shield, if the situation requires.
Eye protection:
Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires.
Eslicarbazepine Acetate

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Crystal- Powder
Form:
Colour: White - Almost white
No data available
Odour:
pH: No data available
Melting point/freezing point:187°C
Boiling point/range: No data available
No data available
Flash point:
Flammability or explosive
limits:
Lower: No data available
No data available
Upper:
Relative density: No data available
Solubility(ies):
[Water] No data available
[Other solvents]
Soluble: Pyridine

---

Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx)
products:

---

Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
No data available
NTP =
Reproductive toxicity: No data available

---

Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
Algae: No data available
Persistence / degradability: No data available
Bioaccumulative No data available
potential(BCF):
Mobility in soil
Log Pow: No data available
Soil adsorption (Koc): No data available
Henry's Law No data available
constant(PaM3/mol):

---

Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.
Eslicarbazepine Acetate

---

Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
UN-No: Not listed

---

Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Eslicarbazepine Acetate（BIA 2093，商品名：Zebinix、Exalief、Stedesa、Aptiom）是一种抗癫痫药物。

体内研究

在latrunculin A诱导的癫痫、痉挛及阵发性脑电活动中，Eslicarbazepine Acetate（ESL）表现出显著的抗痉挛作用。除了直接抑制癫痫发作外，它还具有改善病情的效果，这可能通过调整过度兴奋的神经网络来实现。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	eslicarbazepine acetate	——	C17H16N2O3	296.326
  ——	licarbazepine methoxyacetate	1296102-92-5	C18H18N2O4	326.352
  卡马西平 10,11-环氧化物	carbamazepine 10,11-epoxide	36507-30-9	C15H12N2O2	252.272
  10,11-二氢-10-羟基卡马西平	10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide	29331-92-8	C15H14N2O2	254.288
  艾司利卡西平	S-licarbazepine	104746-04-5	C15H14N2O2	254.288
  (10R)-10,11-二氢-10-羟基-5H-二苯并[b,f]氮杂卓-5-甲酰胺	R-licarbazepine	104746-03-4	C15H14N2O2	254.288
  ——	10-acetoxy-5H-dibenzo[b,f]azepine-5-carboxamide	952740-00-0	C17H14N2O3	294.31
  奥卡西平	oxcarbazepine	28721-07-5	C15H12N2O2	252.272
  ——	(S)-(-)-10,11-dihydro-5H-dibenzo[b,f]azepin-10-ol	——	C14H13NO	211.263

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  艾司利卡西平	S-licarbazepine	104746-04-5	C15H14N2O2	254.288
  奥卡西平	oxcarbazepine	28721-07-5	C15H12N2O2	252.272

反应信息

• 作为反应物：
  描述：

  醋酸艾司利卡西平 在 lithium hydroxide monohydrate 、 水 作用下， 以 甲醇 为溶剂， 生成 艾司利卡西平
  参考文献：
  名称：

  COMPOSITIONS AND METHODS FOR THE TREATMENT OF EPILEPSY AND NEUROLOGICAL DISORDERS

  摘要：

  该发明涉及公式I和公式Ia的化合物，或其药用可接受的多型、溶剂化合物、对映体、立体异构体及其水合物。包括有效量的公式I或公式Ia的药物组合物；以及用于治疗或预防癫痫、抽搐和痉挛的方法可以制备为口服、颊下、直肠、局部、经皮、经粘膜、静脉、体内、糖浆或注射给药。这种组合物可用于治疗癫痫、抽搐和痉挛。

  公开号：

  US20160090379A1
• 作为产物：
  描述：

  奥卡西平 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 乙醇 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 20.67h， 生成 醋酸艾司利卡西平
  参考文献：
  名称：

  一种S-利卡西平的回收方法

  摘要：

  本发明公开了一种S‑利卡西平的回收方法。该回收方法通过手性拆分剂酒石酸酐拆分，获得S‑利卡西平酒石酸酯直接用于制备目标化合物醋酸艾司利卡西平酯。分离出的另一半对应的手性化合物R‑利卡西平酒石酸酯，通过水解获得R‑利卡西平，R‑利卡西平通过光延反应手性翻转化合物获得S‑利卡西平对应的酯，通过水解获得目标化合物S‑利卡西平，进一步与醋酐成酯制备醋酸艾司利卡西平酯，实现S‑利卡西平的回收，从而提高了起始物料奥卡西平的利用率。

  公开号：

  CN116063231A
• 作为试剂：
  描述：

  艾司利卡西平 、 吡啶 、 2-二甲氨基吡啶 、 乙酰氯 在 盐酸 、 水 、 醋酸艾司利卡西平 、 乙酸乙酯 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.0h， 以to obtain the title compound (m. p. 186.0-187.2° C.)的产率得到醋酸艾司利卡西平
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF (S)-(+)- OR (R)-(-)-10-HYDROXY DIHYDRODIBENZ[B,F]AZEPINES BY ENANTIOSELECTIVE REDUCTION OF 10,11-DIHYDRO-10-OXO-5H-DIBENZ[B,F]AZEPINES AND POLYMORPHS THEREOF

  摘要：

  本发明提供了一种新型工艺，用硼酸酯或其衍生物从10,11-二氢-10-氧代-5H-二苯并[b,f]氮杂环制备取代的光学纯(S)-(+)-或(R)-(-)-10-羟基-二氢二苯并[b,f]氮杂环或其衍生物。本发明还提供了利用这些制备的(S)-(+)-或(R)-(-)-10-羟基-二氢二苯并[b,f]氮杂环制备它们的酯，例如(S)-(-)-10-乙酰氧基-10,11-二氢-5H-二苯并[b,f]氮杂环-5-羧酰胺或(R)-(+)-10-乙酰氧基-10,11-二氢-5H-二苯并[b,f]氮杂环-5-羧酰胺。本发明还提供了eslicarbazepine的新型固态结晶形式J1、J2、J3、J4和无定形形式以及其制备工艺。此外，本发明还提供了eslicarbazepine乙酸盐的新型固态结晶形式和无定形形式以及其制备工艺。eslicarbazepine的新型固态形式对于制备eslicarbazepine乙酸盐等衍生物非常有用。

  公开号：

  US20130345198A1

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  申请人：Kandula Mahesh

  公开号：US20160122332A1

  公开（公告）日：2016-05-05

  The invention relates to the compounds of formula I and formula IA or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I and formula IA; and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder (ADHD), schizophrenia, neuropathic pain, seizures, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, Myotonia congenita and post-traumatic stress disorder.

  该发明涉及公式I和公式IA的化合物或其药用可接受盐，以及其多晶型、溶剂合物、对映体、立体异构体和水合物。包括有效量的公式I和公式IA化合物的药物组合物；以及用于口服、颊内、直肠、局部、经皮、经粘膜、静脉内、肠外给药、糖浆或注射的治疗或预防神经系统疾病的方法。这些组合物可用于治疗癫痫、躁郁症、三叉神经痛、注意缺陷多动障碍（ADHD）、精神分裂症、神经痛、癫痫发作、躁郁症、狂躁症、幻肢综合征、复杂性区域性疼痛综合征、阵发性极端疼痛综合征、神经肌痉挛、间歇性爆发障碍、边缘人格障碍、先天性肌张力过高症和创伤后应激障碍。
• 一种抗癫痫药物醋酸艾司利卡西平的制备方法
  申请人：杭州述康生物技术有限公司

  公开号：CN106938986A

  公开（公告）日：2017-07-11

  本发明提供了一种抗癫痫药物醋酸艾司利卡西平的制备方法。本方法以奥卡西平为起始原料，经过还原和乙酰化反应后得到外消旋的醋酸利卡西平，然后连续通过脂肪酶水解和光延反应将外消旋混合物中醋酸艾司利卡西平的对映异构体全部转化为醋酸艾司利卡西平。
• PROCESS FOR THE PREPARATION AND PURIFICATION OF ESLICARBAZEPINE ACETATE AND INTERMEDIATES THEREOF
  申请人：Hirpara Ketan

  公开号：US20150065704A1

  公开（公告）日：2015-03-05

  The present invention provides a novel process for the preparation of 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide, commonly known as oxcarbazepine, which is a medicament and a useful intermediate in the preparation of eslicarbazepine acetate. The present invention further provides a process for the preparation and purification of eslicarbazepine acetate.

  本发明提供了一种新颖的制备10-氧代-10,11-二氢-5H-二苯并[b,f]氮杂环庚-5-甲酰胺，通常称为奥卡西平（oxcarbazepine）的方法，该化合物是一种药物，也是制备艾司卡西平乙酸酯的有用中间体。本发明还提供了一种制备和纯化艾司卡西平乙酸酯的方法。
• One-step lipase-catalysed preparation of eslicarbazepine
  作者：M. F. El-Behairy、E. Sundby

  DOI：10.1039/c6ra23915c

  日期：——

  RS-licarbazepine via lipase catalysed kinetic resolution. A novel stereoselective simultaneous HPLC separations of RS-licarbazepine (1) and its racemic esters RS-2–5 have been developed on Lux® cellulose-2 column using cyclohexane/ethanol 1/1 v/v as mobile phase. The developed enantioselective HPLC separations have been utilized for monitoring of lipase catalyzed kinetic resolution of RS-licarbazepine (1). Lipase

  抗癫痫药依斯卡西平（S -licarbazepine）是由外消旋形式RS-利卡卡西平通过脂肪酶催化的动力学拆分一步制备的。的一种新的立体选择性同时HPLC分离RS -licarbazepine（1）和其外消旋酯RS - 2-5已经对Lux®纤维素-2柱，使用环己烷/乙醇1/1 V / V作为流动相显影。已开发的对映选择性HPLC分离已用于监测脂肪酶催化的RS-利卡西平的动力学拆分（1）。已经进行了脂肪酶催化的酯交换和水解反应。研究了四种不同的酯（乙酸酯（2），丙酸酯（3），丁酸酯（4）和苯甲酸酯（5））的酯交换和水解反应，使用了十种来自多种来源的脂肪酶。用的反式酯化所示的对映体选择性最好RS与以M苯甲酸乙烯酯-licarbazepine吨BE从溶剂和脂肪酶皱褶假丝酵母，其中所述药理学活性对映异构体，小号- （+） -利卡西平，已完成[ ë = 31，EE = 97％，产率84％，α 20 d=
• [EN] PROCESS FOR THE RESOLUTION OF RACEMIC (±)-10,11-DIHYDRO-10-HYDROXY-5H-DIBENZ[B,F]AZEPINE-5-CARBOXAMIDE<br/>[FR] PROCÉDÉ DE RÉSOLUTION RACÉMIQUE (±)-10,11-DIHYDRO -10-HYDROXY -5 H-DIBENZ / B, F / AZÉPINE -5-CARBOXAMIDE
  申请人：WATSON LAB INC

  公开号：WO2012121701A1

  公开（公告）日：2012-09-13

  A process for resolving racemic (±)-10,l l-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5- carboxamide comprising reacting (±)-10,l l-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5- carboxamide with S-ibuprofen or a pharmaceutically acceptable salt thereof to form a mixture of the SS and SR diastereomer esters of 10,l l-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5- carboxamide, followed by separating the SS-ibuprofen ester from the SR ibuprofen ester, and removal of the S-ibuprofen moiety to form S-(+)-10,l l-dihydro-10-hydroxy-5H- dibenz[b,f]azepine-5-carboxamide with a chiral purity greater than 90%.

  将(±)-10,11-二氢-10-羟基-5H-二苯并[b,f]氮杂-5-羧酰胺与S-布洛芬或其药用可接受的盐反应，形成10,11-二氢-10-羟基-5H-二苯并[b,f]氮杂-5-羧酰胺的SS和SR对映异构体酯的混合物，然后将SS-布洛芬酯与SR-布洛芬酯分离，并去除S-布洛芬基团，形成手性纯度大于90%的S-(+)-10,11-二氢-10-羟基-5H-二苯并[b,f]氮杂-5-羧酰胺。