Methods for the synthesis of activated ethylfumarates and their use as intermediates

US10071969B2 · kind B2 · utility

Assignee

• MannKind Corporation · US

Inventors

• Kelly Sullivan Kraft · Hopewell Junction, US
• John J. Freeman · Longmont, US
• Paul Serwinski · Bristol, US
• Vincent Pavia · Valencia, US
• Otto Phanstiel · Oviedo, US
• Navneet Kaur · Chandigarh, IN

Key dates

• Filing date: Nov 23, 2015
• Grant date: Sep 11, 2018
• Expiry date: Nov 23, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C201/12
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.