2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one Chemical Properties

Melting point:

176 - 178°C

Boiling point:

428.0±34.0 °C(Predicted)

Density 

1.346±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

pka

0.82±0.20(Predicted)

color 

Yellow to Dark Yellow

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C13H14ClN3O/c1-8-6-11(18)17(9-4-2-3-5-9)12-10(8)7-15-13(14)16-12/h6-7,9H,2-5H2,1H3

InChIKey

BSKNQSYIDZUXQT-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=C2C(C)=CC(=O)N(C3CCCC3)C2=N1

2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one Usage And Synthesis

Description

2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one is used as an intermediate for Palbociclib, a CDK 4/6 inhibitor used to treat patients with hormone receptor (HR)-positive, HER-2-negative advanced or metastatic (cancer that has spread) breast cancer.

Uses

2-Chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one is used as pharmaceutical intermediate.

Synthesis

To the reaction vessel was added 5-bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine (10.0 g, 1.0 eq.) and N-methylpyrrolidone (NMP, 50 mL, 5.0 vol.) at room temperature. Subsequently, crotonic acid (4.7 g, 1.5 eq.) and triethylamine (20.2 mL, 4.0 eq.) were added to the reaction mixture. The vessel was degassed and purged three times with nitrogen. Palladium acetate (Pd(OAc)2, 0.25 g, 0.03 eq.) was added to the degassed reaction mixture. The vessel was again degassed and purged with nitrogen three times in the same manner. The reaction mixture was heated to 65 °C and stirred continuously until the feedstock was completely consumed (at least 6 hours). Then, acetic anhydride (6.8 mL, 2.0 eq.) was added to the reaction mixture. The reaction was kept at 65 °C until the feedstock was completely consumed (usually takes 1-2 hours). Upon completion of the reaction, the mixture was cooled to 20 °C and water (100 mL, 10 v/v) was added to dissolve the triethylamine-HBr salt while 2-chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7(8H)-one was precipitated. The precipitate was stirred at 20°C for 1 hour. The solid was collected by filtration and washed sequentially with a mixture of water (20 mL, 2.0 v/v) and isopropanol/water (4:1, 50 mL, 5.0 v/v). Finally, the crude product was vacuum dried at 55-70 °C to afford 2-chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7(8H)-one (7.8 g, 81% yield) as a tan to gray solid.

References

[1] Patent: WO2014/128588, 2014, A1. Location in patent: Page/Page column 34; 35
[2] Patent: WO2008/32157, 2008, A2. Location in patent: Page/Page column 26

2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one(1013916-37-4)Related Product Information

• 4-[6-[(8-cyclopentyl-6-ethenyl-7,8-dihydro-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl]-1-piperazinecarboxylic acid tert-butyl ester
• 4-(5-AMINOPYRIDIN-2-YL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER
• 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
• 2-Amino-5-bromopyridine
• Palbociclib Impurity 7
• 4-[6-(6-BROMO-8-CYCLOPENTYL-5-METHYL-7-OXO-7,8-DIHYDRO-PYRIDO[2,3-D]PYRIMIDIN-2-YLAMINO)-PYRIDIN-3-YL]-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER
• Pyrido[2,3-d]pyriMidin-7(8H)-one, 8-cyclopentyl-5-Methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]aMino]-
• Phosphine oxide, tris (2-methylphenyl)-
• tert-butyl 4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate
• 1-Piperazinecarboxylic acid, 4-(2-aMino-3-pyridinyl)-, 1,1-diMethylethyl ester
• 5-(piperazin-1-yl)pyridin-2-aMine
• 571188-59-5
• 8-cyclopentyl-6-(1-hydroxyethyl)-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one
• 1,4-bis(4-nitrophenyl)piperazine
• 1-(5-Nitropyridin-2-yl)piperazine
• 6-broMo-8-cyclopentyl-5-Methyl-2-(5-(piperazin-1-yl)pyridin-2-ylaMino)pyrido[2,3-d]pyriMidin-7(8H)-one