ChemicalBook CAS DataBase List 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methyl-purine-2,6 -dione

8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methyl-purine-2,6 -dione synthesis

9synthesis methods

Product Name:8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methyl-purine-2,6 -dione
CAS Number:155270-99-8
Molecular formula:C20H24N4O4
Molecular Weight:384.43

Istradefylline (KW-6002) is a selective antagonist at the A2A receptor. It has been found to be useful in the treatment of Parkinson's disease. Istradefylline reduces dyskinesia resulting from long-term treatment with classical antiparkinson drugs such as levodopa. Istradefylline is an analog of caffeine. Synthetic Description Reference: Li, Fan; Hou, Xingpu; Li, Lin; Lu, Tao; Du, Yumin. Synthesis of antiparkinsonian agent istradefylline. Zhongguo Yiyao Gongye Zazhi. Volume 41. Issue 4. Pages 241-243. Journal. (2010). Synthetic Description Reference: LaBeaume, Paul; Dong, Ma; Sitkovsky, Michail; Jones, Elizabeth V.; Thomas, Rhiannon; Sadler, Sara; Kallmerten, Amy E.; Jones, Graham B. An efficient route to xanthine based A2A adenosine receptor antagonists and functional derivatives. Organic & Biomolecular Chemistry. Volume 8. Issue 18. Pages 4155-4157. Journal. (2010). Synthetic Description Reference: Jorg, Manuela; Shonberg, Jeremy; Mak, Frankie S.; Miller, Neil D.; Yuriev, Elizabeth; Scammells, Peter J.; Capuano, Ben. Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space. Bioorganic & Medicinal Chemistry Letters. Volume 23. Issue 11. Pages 3427-3433. Journal; Online Computer File. (2013). Synthetic Description Reference : Dong, Dandan. Method for preparing istradefylline crystal form III by ball milling. CN 108117554. (2018). Synthetic Description Reference: Wang, Zhenyu; Liu, Yanhua. Process for preparation of istradefylline. Assignee Hangzhou SIMBOS Pharmaceutical Co., Ltd., Peop. Rep. China. CN 106632332. (2017).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

Reference: Li, Fan; Hou, Xingpu; Li, Lin; Lu, Tao; Du, Yumin. Synthesis of antiparkinsonian agent istradefylline. Zhongguo Yiyao Gongye Zazhi. Volume 41. Issue 4. Pages 241-243. Journal. (2010).

8-[(1E)-2-(3,4-Dimethoxyphenyl)ethenyl]-1,3-diethyl-3,9-dihydro-1H-purine-2,6-dione

155270-98-7
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74-88-4
339 suppliers
$15.00/10g

8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methyl-purine-2,6 -dione

155270-99-8
209 suppliers
$50.00/250 mg

Yield:155270-99-8 99%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 50; for 5 h;

Steps:

1 Preparation Example 1: Preparation of crude istradefylline
Under the mechanical stirring, into 3L reaction flask, add intermediate II 50g (0.135 mol), potassium carbonate 28g (0.203 mol), N,N-dimethylformamide 550 ml and iodomethane 15 ml (0.241 mol), heated to 50 °C, stirring reaction 5h, cooled to 0 °C, add purified water to the reaction solution in 550 ml. Filtering, cake purified water 1.1L after washing, 45 °C lower vacuum drying, to obtain 51.3g pale yellow solid, yield 99%, HPLC purity 98.6%, used in the following istradefylline A crystal preparation.

References:

CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.;Gong, Denghuang;Wang, Jie;Ge, Jinghua;Yang, Jie;Sun, Wenjiao;Yang, Min;Yang, Chunqiao;Ma, Yuxiu CN106279169, 2017, A Location in patent:Paragraph 0044; 0045; 0046

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