Identification | Back Directory | [Name]
2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one | [CAS]
1013916-37-4 | [Synonyms]
-5-methyL oro-8-cycL 3-d]pyriMidin-7(8H)-one Palbociclib Intermediate2 Palbociclib intermediates 2-chloro-8-cyclopentyl-5-Me pyrido[2,3-d]pyrimidin-7(8H)-one 2-chloro-8-cyclopentyl-5-Methylpyrido[2 2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7-one 2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one 2-Chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one Pyrido[2,3-d]pyriMidin-7(8H)-one, 2-chloro-8-cyclopentyl-5-Methyl- 2-chloro-8-cyclopentyl-5-methyl-7H,8H-pyrido[2,3-d]pyrimidin-7-one 2-Chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one,97% 2-Chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (For Palbociclib) | [EINECS(EC#)]
800-066-8 | [Molecular Formula]
C13H14ClN3O | [MDL Number]
MFCD13181207 | [MOL File]
1013916-37-4.mol | [Molecular Weight]
263.723 |
Chemical Properties | Back Directory | [Melting point ]
176 - 178°C | [Boiling point ]
428.0±34.0 °C(Predicted) | [density ]
1.346±0.06 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,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 |
Hazard Information | Back Directory | [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 |
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