ChemicalBook CAS DataBase List Brivaracetam

Brivaracetam synthesis

1synthesis methods

Product Name: Brivaracetam
CAS Number:357336-20-0
Molecular formula:C11H20N2O2
Molecular Weight:212.29

Brivaracetam, also known as UCB 34714, is a chemical analog of levetiracetam, is a racetam derivative with anticonvulsant (antiepileptic) properties approved for the treatment of epilepsy. Brivaracetam was discontinued. Synthetic Description Reference: Qiu S, Tehrani KA, Sergeyev S, Bultinck P, Herrebout W, Mathieu B. Stereochemistry of the Brivaracetam Diastereoisomers. Chirality. 2016 Mar;28(3):215-25. doi: 10.1002/chir.22558. Epub 2016 Jan 6. PubMed PMID: 26740317. Synthetic Description Reference: Huang, Shaozhi; Shi, Lei; Chen, Yiwen; Xu, Yawen. Method for preparing brivaracetam. CN 105646319. (Assignee Foshan Longxin Pharmaceutical Science and Technology Co., Ltd., Peop. Rep. China) Synthetic Description Reference: Wang, Chunyan; Chen, Zhiyong; Wang, Cong. Preparation method of brivaracetam and its intermediate. CN 106748950. (Assignee Chengdu Miracle Pharmaceutical Co., Ltd., Peop. Rep. China) Synthetic Description Reference: Liu, Xingxin; Wu, Liming; Li, Qian; Xiao, Jianyang; Guo, Peng. Synthesis method of brivaracetam from pentanoic acid or pentoyl halide. CN 107216276. (Assignee AstaTech (Chengdu) Biopharmaceutical Co., Ltd., Peop. Rep. China) Synthetic Description Reference: Kenda BM, Matagne AC, Talaga PE, Pasau PM, Differding E, Lallemand BI, Frycia AM, Moureau FG, Klitgaard HV, Gillard MR, Fuks B, Michel P. Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J Med Chem. 2004 Jan 29;47(3):530-49. PubMed PMID: 14736235. Synthetic Description Reference: Ates, Celal; Lurquin, Francoise; Quesnel, Yannick; Schule, Arnaud. Preparation of 4-substituted-pyrrolidin-2-ones and their uses for the synthesis of 2-oxo-pyrrolidin-1-yl derivatives. WO 2007031263. (Assignee UCB S. A., Belg.) Synthetic Description Reference: Schule, Arnaud; Merschaert, Alain; Szczepaniak, Christophe; Marechal, Christophe; Carly, Nicolas; O'Rourke, John; Ates, Celal. A Biocatalytic Route to the Novel Antiepileptic Drug Brivaracetam. Organic Process Research & Development. (UCB Pharma S.A.) Synthetic Description Reference: Ates, Celal; Schule, Arnaud. Preparation of 1-carbamoylalkyl-3-carboxy-2-oxopyrrolidines. WO 2007065634. (Assignee UCB Pharma, S. A., Belg.) Synthetic Description Reference: Wang, Peng; Li, Pixu; Wei, Qiang; Liu, Yuanhua. Processes to produce brivaracetam. WO 2016191435. Synthetic Description Reference: Defrance, Thierry; Septavaux, Jean; Nuel, Didier. Process for preparing brivaracetam. WO 2017076738. (Assignee UCB Biopharma Sprl, Belg.) Synthetic Description Reference: Kumar, Pramod; Sankareswaran, Srimurugan; Mannam, Madhavarao; Gaddam, Venugopal Reddy; Chiluukuru, Srikanth; Chaubey, Bipin Kumar. Novel process for the preparation of Brivaracetam. WO 2018042393. (Assignee Micro Labs Limited, India)

Synthetic Routes

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ROUTE 2

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ROUTE 4

ROUTE 5

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ROUTE 8

ROUTE 9

ROUTE 10

ROUTE 11

ROUTE 12

Reference: Qiu S, Tehrani KA, Sergeyev S, Bultinck P, Herrebout W, Mathieu B. Stereochemistry of the Brivaracetam Diastereoisomers. Chirality. 2016 Mar;28(3):215-25. doi: 10.1002/chir.22558. Epub 2016 Jan 6. PubMed PMID: 26740317.

Ciceri, Samuele; Grisenti, Paride; Elahi, Shahrzad Reza; Ferraboschi, Patrizia. A new chemoenzymatic synthesis of the chiral key intermediate of the antiepileptic brivaracetam. Molecules.Volume 23. Issue 9.Pages 2206/1-2206/11. 2018.

357338-13-7 Synthesis

(S)-2-(2-oxo-4-propyl-2,5-dihydro-1H-pyrrol-1-yl)butanamide

357338-13-7
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357336-20-0
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Yield:357336-20-0 99.3%

Reaction Conditions:

with (R)-(-)-5,5'-bis[di(3,5-ditert-butyl-4-methoxyphenyl)phosphino]-4,4'-bi-1,3-benzodioxole;copper chloride (I);sodium tertiary butoxide in toluene at -40; for 24 h;Inert atmosphere;

Steps:

1

(2S) -2- ((4R) -2-oxo-4-n-propyl-1-pyrrolidinyl) butanamide,Which comprises the following steps: adding 430 mg of cuprous chloride, 420 mg of sodium tert-butoxide, 120 mg of (R) -DTBM-SEGPH0S to the reaction vessel under the protection of nitrogen And 240 ml of toluene, stirred for 20 min; then the temperature was adjusted to -40 ° C, 60 g of the starting material was added,(2S) - (2-oxo-4-propyl-2,5-dihydro-1-pyrrolyl) butanamide; and the reaction mixture was added 40 ml of polymethylhydrogensiloxane (S0 0.67 mil of polymethylhydrogensiloxane) and then incubated at a temperature of -40 ° C After 24 hours of reaction, the temperature was adjusted to 0 ° C, then 100 ml of saturated sodium bicarbonate solution and 150 ml of ether were added, And then stirring l0h; then, the use of ether on the reaction material extraction 2 times, combined with 2 extracted organic layer, and then there will beThe machine bed is dried, filtered, concentrated to obtain the product. 58 g of crude product was weighed and then recrystallized using isopropyl ether, 49 g of product was obtained, and the product after recrystallization was detected by high performance liquid chromatography. The detection conditions were: 0D-HColumn, n-hexane: isopropanol (90:10) as mobile phase, tassel is 1.01111 / 1 ^ 11, detection wavelength is 210 brain, detected by 4(R) type chiral material (i.e., (2S) -2- ((4R) -2-oxo-4-n-propyl-1-pyrrolidinyl) butanamide) 99.3%.

References:

CN104892483,2017,B Location in patent:Paragraph 0029-0030

Brivaracetam Related Search:

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