US 12,134,589 B2
Process for the production of substituted 2-[2-(phenyl) ethylaminojalkaneamide derivatives
Wolfgang Skranc, Vienna (AT); Michael Wolberg, Neutraubling (DE); Matthias Riepl, Altenhann (DE); Christoph Imboden, Hofstetten Solothurn (CH); and Erwin Waldvogel, Aesch (CH)
Assigned to Newron Pharmaceuticals S.p.A., Bresso (IT)
Appl. No. 17/603,454
Filed by Newron Pharmaceuticals S.p.A., Bresso (IT)
PCT Filed Apr. 8, 2020, PCT No. PCT/EP2020/060037
§ 371(c)(1), (2) Date Oct. 13, 2021,
PCT Pub. No. WO2020/212227, PCT Pub. Date Oct. 22, 2020.
Claims priority of application No. 19169714 (EP), filed on Apr. 17, 2019.
Prior Publication US 2022/0177417 A1, Jun. 9, 2022
Int. Cl. C07C 231/12 (2006.01)
CPC C07C 231/12 (2013.01) 17 Claims
 
1. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof:

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wherein R is (C3-C10)alkyl, or ω-trifluoro(C3-C10)alkyl;
R1 and R2 are, independently, hydrogen, hydroxy, (C1-C8)alkoxy, (C1-C8) alkylthio, halo, trifluoromethyl or 2,2,2-trifluoroethyl; or one of R1 and R2 is at the ortho position to the R—O— group and, taken together with the same R—O—, represents a

OG Complex Work Unit Chemistry
group where R0 is (C2-C9)alkyl;
R3 and R4 are independently hydrogen or (C1-C6)alkyl; or taken together with the adjacent nitrogen atom form a 5-6 membered monocyclic saturated heterocycle, optionally containing one additional heteroatom chosen among —O—, —S— and —NR7— where R7 is hydrogen or (C1-C6) alkyl;
R5 is hydrogen or (C1-C6)alkyl;
and wherein optionally one or more hydrogen atom in the groups R, R1, R2, R3, R4 and R5 can be substituted by a deuterium atom;
said process comprising the steps of:
i) reacting a compound of formula (II) or a salt thereof

OG Complex Work Unit Chemistry
wherein R, R1, R2, are as above defined, with a compound of formula (III):

OG Complex Work Unit Chemistry
wherein R3, R4 and R5 are as above defined, under reducing conditions, to obtain the compound of formula (I) as above defined, and
ii) optionally salifying the obtained compound of formula (I).