866084-31-3

Basic information

• Product Name: tert-butyl 4-(6-(8-cyclopentyl-5-Methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyriMidin-2-ylaMino)pyridin-3-yl)piperazine-1-carboxylate
• Synonyms: tert-butyl 4-(6-(8-cyclopentyl-5-Methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyriMidin-2-ylaMino)pyridin-3-yl)piperazine-1-carboxylate;Palbociclib INT;tert-butyl 4-(6-((6-(1-butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate;4-[6-[[6-(1-Butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino]pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester;2-Methyl-2-propanyl 4-(6-{[8-cyclopentyl-5-methyl-7-oxo-6-(1-prop oxyvinyl)-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-3-pyridin yl)-1-piperazinecarboxylate
• CAS NO: 866084-31-3
• Molecular Formula: C32H43N7O4
• Molecular Weight: 589.72832
• Product Categories: Anticancer
• Mol File: 866084-31-3.mol
• Article Data: 19

Chemical Properties

• Boiling Point: 764.2±70.0 °C(Predicted)
• Appearance: /
• Density: 1.224±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• PKA: 5.24±0.10(Predicted)
• CAS DataBase Reference: tert-butyl 4-(6-(8-cyclopentyl-5-Methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyriMidin-2-ylaMino)pyridin-3-yl)piperazine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-butyl 4-(6-(8-cyclopentyl-5-Methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyriMidin-2-ylaMino)pyridin-3-yl)piperazine-1-carboxylate(866084-31-3)
• EPA Substance Registry System: tert-butyl 4-(6-(8-cyclopentyl-5-Methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyriMidin-2-ylaMino)pyridin-3-yl)piperazine-1-carboxylate(866084-31-3)

Safety Data

• Hazardous Substances Data: 866084-31-3(Hazardous Substances Data)

Usage

Uses

tert-Butyl 4-[6-[[6-(1-Butoxyethenyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl]amino]-pyridin-3-yl]-piperazine-1-carboxylate is an intermediate in the commercial development of palbociclib, a highly selective reversible inhibitor of CDK 4/6 for breast cancer treatment.

Upstream product

• 571188-81-3 6?bromo?8?cyclopentyl?5?methyl?2?(methylsulfinyl)pyrido[2,3?d]pyrimidin?7(8H)?one 
• 362656-23-3 8?cyclopentyl?5?methyl?2?(methylthio)pyrido[2,3?d]pyrimidin?7(8H)?one 
• 733039-23-1 5?bromo?N?cyclopentyl?2?(methylthio)pyrimidin?4?amine 
• 571188-59-5 tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate 
• 1016636-76-2 2-chloro-5-methyl-6-bromo-8-cyclopentylpyridine[2,3-d]pyrimidin-8-hydro-7-one 
• 111-34-2 -butyl vinyl ether 
• 571189-16-7 4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 39856-50-3 5-bromo2-nitropyridine 
• 1013916-37-4 2-chloro-5-methyl-8-cyclopentylpyridin[2,3-d]pyrimidin-8-hydro-7-one 
• 733039-20-8 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine 
• 1003-03-8 Cyclopentamine 
• 571188-82-4 tert?butyl 4?(6?((6?bromo?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate 

Downstream Products

• 571190-30-2 PD 0332991 
• 1651214-74-2 4-[6-(6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridine-3-yl]piperazine-1-carboxylic acid tert-butyl ester 
• 827022-33-3 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one isethionate 
• 827022-33-3 PD 0332991 isethionate 
• 827022-33-3 C₂₄H₂₉N₇O₂*2C₂H₆O₄S 

Relevant articles and documents

Palbociclib Commercial Manufacturing Process Development. Part II: Regioselective Heck Coupling with Polymorph Control for Processability

A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, reversible inhibitor of CDK 4/6. The second step, which utilizes a Heck coupling to install the enol ether side chain, is described. A highly regioselective catalyst was identified for this transformation along with reaction conditions that ensure robustness upon scale-up. Effective removal of palladium was accomplished via filtration of insoluble metal and an extractive chelation step. Finally, efficient isolation of coupled product 3 was achieved through careful polymorph control via seeding and an optimized cooling protocol that avoids nucleation of a kinetically favored, slow-filtering polymorph.

A new route for the synthesis of Palbociclib

Abstract: In this paper, a novel synthetic method for Palbociclib was reported. It was synthesized in eight steps from 2-(methylthio) pyrimidin-4-(3H)-one with approximately 10% overall yield. This protocol started material 2-(methylthio) pyrimidin-4-(3H)-one, involved nucleophilic substitution by thionyl chloride, bromination, nucleophilic substitution by cyclopentylamine, a one pot-two step method (Heck reaction, ring close sequence), oxidation and bromination, cross-coupling reaction, Heck reaction, aqueous workup to afford Palbociclib. This synthetic route used inexpensive raw material and reagents, involved readily controllable reaction conditions and reduced environmental hazards. Graphic abstract: Synthesis of Palbociclib, a small molecule CDK inhibitor, starting from 2-(methylthio) pyrimidin-4-(3H)-one by 8 steps reaction. This method afforded the Palbociclib in 10% yield. [Figure not available: see fulltext.].

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

A focused PROTAC library hijacking cancer therapeutic target CDK6 was developed. A design principle as "match/mismatch" was proposed for understanding the degradation profile differences in these PROTACs. Notably, potent PROTACs with specific and remarkable CDK6 degradation potential were generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. The PROTAC strongly inhibited proliferation of hematopoietic cancer cells including multiple myeloma and robustly degraded copy-amplified/mutated forms of CDK6, indicating future potential clinical applications.