ChemicalBook CAS DataBase List Safinamide

Safinamide synthesis

9synthesis methods

Product Name:Safinamide
CAS Number:133865-89-1
Molecular formula:C17H19FN2O2
Molecular Weight:302.34

Safinamide, also known as FCE-26743 and EMD-1195686, is a drug indicated for the treatment of Parkinson's disease with multiple methods of action. Potential additional uses might be restless legs syndrome (RLS) and epilepsy. Safinamide is a reversible and selective monoamine oxidase B inhibitor, reducing degradation of dopamine, and a glutamate release inhibitor. It also inhibits dopamine reuptake. Additionally, safinamide blocks sodium and calcium channels. Safinamide has been approved by the European Medicines Agency for the treatment of adult patients with idiopathic Parkinson’s disease as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD drugs in patients with mid-to-late-stage fluctuating disease. Synthetic Description Synthetic Description Reference: Murugan, Muthukrishnan; Mohammad, Mujahid. An improved enantioselective and regioselective process for preparation of anti-parkinson agent safinamide and its analogues. WO 2014178083. (Council of Scientific & Industrial Research, India) Synthetic Description Reference: Barbanti, Elena; Faravelli, Laura; Salvati, Patricia; Canevotti, Renato; Ponzini, Francesco. Process for the production of highly pure 2-[4-(3- or 2-fluorobenzyloxy)benzylamino]propanamides as cytochrome P450 inhibitors and their pharmaceutical compositions and use in the treatment of diseases. WO 2009074478. (Newron Pharmaceuticals S.p.A., Italy) Synthetic Description Reference: Barbanti, Elena; Caccia, Carla; Salvati, Patricia; Velardi, Francesco; Ruffilli, Tiziano; Bogogna, Luigi. Process for the production of 2-[4-(3- and 2-fluorobenzyloxy) benzylamino]propanamides. US 20090156678. (Newron Pharmaceuticals S.p.A., Italy) Synthetic Description Reference: Barbanti, Elena; Caccia, Carla; Salvati, Patricia; Velardi, Francesco; Rufilli, Tiziano; Bogogna, Luigi. Process for the production of 2-[4-(3- and 2-fluorobenzyloxy)benzylamino]propanamides (safinamide and ralfinamide) of high purity by catalytic hydrogenation of Schiff base intermediates and their use for treating CNS disorders. WO 2007147491. (Newron Pharmaceuticals S.p.A., Italy)

Synthetic Routes

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ROUTE 2

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Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T.; Wang, Yuying; Ripsch, Matthew S.; White, Fletcher A.; Khanna, Rajesh; Kohn, Harold. Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide. Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy. (ACS Chemical Neuroscience Volume 6 Issue 2)

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Yield:133865-89-1 96%

Reaction Conditions:

with potassium borohydride in methanol;

Steps:

2 Example 2

A solution of L-alanine amide hydrochloride 84. 41 g (0.68 mol) was added to the reaction flask,Triethylamine 171 · 42 g (l. 69 mol)Methanol 1300ml, room temperature stirring 30min,Then add 4- (3-fluorobenzyloxy) benzaldehyde 130. llg (0. 56 mol) and stirred at room temperature for 2 h.Then add KBH4 182. 71g (3. 39mol) and stir well overnight.After completion of the reaction, the reaction solution was concentrated to dryness,Add 1300ml water room temperature stirring 1h, pumping filter,40 ° C in vacuo for 4 h to give a white solid (S) -2- [4- (3-fluorobenzyloxy)Benzylamino] propanamide 163. 92 g, yield: 96.0%. HPLC purity: 99.04%.

References:

CN106565520,2017,A Location in patent:Paragraph 0016

66742-57-2 Synthesis