1035556-22-9

Basic information

• Product Name: 3-benzyl-6-(methylamino)pyrimidin-4(3H)-one
• Synonyms: 3-benzyl-6-(methylamino)pyrimidin-4(3H)-one
• CAS NO: 1035556-22-9
• Molecular Weight: 215.255
• Mol File: 1035556-22-9.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 3-benzyl-6-(methylamino)pyrimidin-4(3H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3-benzyl-6-(methylamino)pyrimidin-4(3H)-one(1035556-22-9)
• EPA Substance Registry System: 3-benzyl-6-(methylamino)pyrimidin-4(3H)-one(1035556-22-9)

Safety Data

• Hazardous Substances Data: 1035556-22-9(Hazardous Substances Data)

Upstream product

• 1122-67-4 6-(methylamino)pyrimidin-4(3H)-one 
• 100-39-0 benzyl bromide 
• 698-82-8 3-methyl-6-methylamino-3H-pyrimidin-4-one 

Downstream Products

• 1035556-23-0 3-benzyl-5-hydroxy-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035556-35-4 3-benzyl-5-hydroxy-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035556-41-2 3-benzyl-6-fluoro-5-(2-fluoro-4-nitrophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1286748-45-5 C₂₁H₁₅F₂IN₄O₂ 
• 1035556-43-4 5-(2-fluoro-4-iodophenylamino)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-51-1 (R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-50-0 (S)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-83-9 3-(2-(dimethylamino)ethyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1286747-87-2 C₁₇H₁₅ClFIN₄O₄ 
• 1035555-63-5 TAK-733 
• 1035555-65-7 (R)-5-(4-bromo-2-fluorophenylamino)-3-(2,3-dihydroxypropyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-67-9 (R)-3-(2,3-dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-64-6 (S)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 
• 1035555-62-4 6-fluoro-5-(2-fluoro-4-iodophenylamino)-3-(2-hydroxyethyl)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 

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.

MAPK/ERK KINASE INHIBITORS

Compounds of the following formula are provided for use with MEK (I): wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.