1227054-01-4

Basic information

• Product Name: (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione
• Synonyms: (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione
• CAS NO: 1227054-01-4
• Molecular Weight: 544.297
• Mol File: 1227054-01-4.mol

Chemical Properties

• CAS DataBase Reference: (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione(1227054-01-4)
• EPA Substance Registry System: (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione(1227054-01-4)

Safety Data

• Hazardous Substances Data: 1227054-01-4(Hazardous Substances Data)

Upstream product

• 1227053-99-7 5-chloro-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1227054-02-5 (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-nitrobenzenesulfonate 
• 1227053-98-6 2-amino-4-chloro-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carbonitrile 
• 14347-78-5 1,2-O-isopropylidene-D-glycerol 
• 1402613-56-2 C₇H₆FN₃O₂ 
• 1227053-96-4 C₇H₅FN₂O₃ 
• 1227053-97-5 2-amino-5-fluoro-4-hydroxy-1-methyl-6-oxo-1,6-dihydropyridine-3-carbonitrile 
• 1227054-00-3 (R)-5-chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7-(3H,8H)-dione 
• 29632-74-4 2-fluro-4-iodoaniline 

Downstream Products

• 1035555-63-5 TAK-733 

Relevant articles and documents

Process research and kilogram synthesis of an investigational, potent MEK inhibitor

TAK-733 (1) is an investigational, novel MEK kinase inhibitor that bears a 6-fluoropyridopyrimidone core. Process research of 1 was conducted, and an efficient, scalable route was developed. The key intermediate, a multisubstituted fluoropyridone, was formed in one pot via a three-step cascade reaction: condensation between a-fluoromalonate and malononitrile, methyl amide formation, and intramolecular cyclization. Chlorination of the hydroxyl functionality and cyclization with formic acid provided the desired pyridopyrimidone core in high yield. Subsequent N-alkylation with the nosylate of (R)-glycerol acetonide and displacement of the chlorine with 2-fluoro-4-iodoaniline proceeded successfully with good yields. Final acid-catalyzed deprotection of the acetonide functionality followed by a controlled crystallization protocol afforded the active pharmaceutical ingredient (API) with the desired polymorph. Compared to the initial synthesis, this route was more concise (six steps compared to the original nine steps), and the overall yield was improved significantly (from 3% to 25%). These improvements allowed for production of multikilograms of 1.

PROCESS FOR MAKING (R)-3-(2,3-DIHYDROXYPROPYL)-6-FLUORO-5-(2-FLOURO-4-IODOPHENYLAMINO)-8-METHYLPYRIDO[2,3-d]PYRIMIDINE-4,7(3H,8H)-DIONE AND INTERMEDIATES THEREOF

The present invention relates generally to processes of making (R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione, intermediates thereof, and a process for making a particular polymorph of (R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione.