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US 10,689,332 B2Granted
Racemic beta-aminosulfone compounds
AssigneeQuimica Sintetica, S.A.
InventorsGiuseppe Barreca, Giovanni Marras, Fabio Morana
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Abstract
It is described an industrially viable and advantageous process for the preparation of racemic beta-aminosulfone (1), an useful intermediate for the preparation of N-(2-((1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl)acetamide, also known as Apremilast, the latter being suitable for use in methods of treating, preventing and/or managing psoriasis or psoriatic arthritis.
Claims18
A process for preparing racemic beta-aminosulfone of formula (I),
- the process comprising:
- a) reacting 3-ethoxy-4-methoxybenzaldehyde of formula (9) with a compound of formula R1—NH2 and a compound of formula R2—S(O)OH or a salt thereof to obtain an aminosulfone of formula (2):
- wherein:
- R1 is an amino protecting group;
- and
- R2 is a C1-C6 alkyl, a substituted C1-C6 alkyl, a C6-C10 aryl or a substituted C6-C10 aryl;
- b) converting the aminosulfone of formula (2) into a sulfone of formula (3) by treatment with a carbanion derived from dimethyl sulfone:
- and
- c) deprotecting the sulfone of formula (3) to obtain 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1-amine of formula (1) in the form of a racemic mixture.
6 more elements
An Imine of formula (10):
- wherein R1 is an amino protecting group which forms, together with the nitrogen atom to which it is linked, a carbamate, an amide, or a phosphinoamide group.
Sulfone of formula (3):
- wherein R1 is a tert-butoxycarbonyl or a benzyloxycarbonyl group.
Dependencies are inferred from the claim text.