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US 2022/0033365 A1Published application
Process for the preparation of sphingosine-1-phosphate receptor agonist
AssigneeQuimica Sintetica, S.A.
InventorsGiuseppe BARRECA, Luca CARCONE, Maurizio TADDEI, Damian Mark GRAINGER, Samantha Louise STANILAND, Claudio CIANFEROTTI, Giovanni MARRAS
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Abstract
Industrially viable and advantageous processes for the preparation of Ozanimod are described. The invention also discloses the intermediates obtained in the process.
Claims19
A process for the preparation of a compound of general formula (7) or a salt thereof, said process comprising:
- a) reacting an indanone of general formula (1) with a compound of general formula (2) so as to provide a compound of general formula (3);
- b) converting said compound of general formula (3) into a compound of general formula (7) or a salt thereof;
- wherein:
- R1 is selected from the group consisting of —CN and 1,2,4-oxadiazole, said 1,2,4-oxadiazole being attached to the bicycle via carbon 3 and optionally substituted in position 5 with a 3′-cyano-4′-isopropoxyphenyl group;
- one of the dashed lines indicates a single bond and the other one a double bond,
- when the dashed line linked to R2 is a double bond, R2 is N, and when the dashed line linked to R2 is a single bond, R2 is NH;
- R10 is selected from the group consisting of —CH2OH, —CH2OPg and —CO2R12;
- R12 is selected from the group consisting of H, a linear or branched (C1-C8)alkyl or a linear or branched (C1-C8)alkyl substituted with a (C6-C10)aryl;
- Pg is an oxygen protecting group;
- and
- the * indicates a stereogenic center;
- wherein step a) is carried out in the absence of titanium alkoxides.
9 more elements
Compound of formula:
- wherein:
- R1 is selected from the group consisting of —CN and 1,2,4-oxadiazole, said 1,2,4-oxadiazole being attached to the bicycle via carbon 3 and optionally substituted in position 5 with a 3′-cyano-4′-isopropoxyphenyl group;
- R2 is selected from the group consisting of N and NH;
- R3 and R4 are, independently of each other, hydrogen or a linear or branched (C1-C6)alkyl;
- R5 and R6 are, independently of each other, a linear or branched (C1-C8)alkyl;
- R7 is selected from the group consisting of a linear or branched (C1-C8) alkyl, a linear or branched (C1-C8)alkyl substituted with a (C6-C10)aryl, R8C(O)— and (R9)3Si—;
- R8, and R9 are, independently of each other, a linear or branched (C1-C8)alkyl or a linear or branched (C1-C8)alkyl substituted with a (C6-C10)aryl;
- R10 is selected from the group consisting of —CH2OH, —CH2OPg and —CO2R12;
- R11 is imidazole;
- R12 is selected from the group consisting of H, a linear or branched (C1-C8)alkyl and a linear or branched (C1-C8)alkyl substituted with a (C6-C10)aryl;
- R13 is selected from the group consisting of H and Pg;
- R14 is —CO2R12;
- R16 is a nitrogen protecting group;
- the dashed lines indicate, independently of each other, a single or a double bond;
- Pg is an oxygen protecting group;
- Y together with the carbon atom to which it is bonded forms a cyclic ketal a ketal or an enol ether;
- the * indicates a stereogenic center;
- Z is (CR3R4)n;
- and
- n is 2 or 3;
- with the proviso that:
- when the dashed line linked to R2 is a double bond R2 is N, and when the dashed line linked to R2 is a single bond R2 is NH;
- in the compounds of formula (3), (3A) and (3B), one of the dashed lines indicates a single bond and the other one a double bond,
- in the compounds of formula (4), (5), (6) and (6′), when the dashed line indicates a double bond, Y, together with the carbon atom to which it is linked, forms an enol ether;
- in the compound of formula (7A″) R13 is Pg;
- and
- in the compound of formula (7B″) R4 is different from —CO2H.
24 more elements
Dependencies are inferred from the claim text.