Abemaciclib

Abemaciclib is a pivotal CDK4/6 inhibitor API that has transformed the treatment landscape for HR+/HER2- breast cancer. As an orally bioavailable small molecule, Abemaciclib exerts its therapeutic effect through selective inhibition of CDK4 and CDK6, thereby arresting tumor cell proliferation. The unique chemical structure of Abemaciclib—featuring a 2-aminopyrimidine core with a benzimidazole substituent—enables potent target engagement with IC₅₀ values in the low nanomolar range. In pharmaceutical manufacturing, Abemaciclib serves as the final active pharmaceutical ingredient, with stringent quality requirements to ensure batch-to-batch consistency and therapeutic efficacy. The synthetic route to Abemaciclib typically involves palladium-catalyzed cross-coupling reactions including Suzuki coupling and Buchwald-Hartwig amination, followed by reductive amination as the final step. For generic manufacturers and research institutions, Abemaciclib represents both a high-value API and a compound of significant synthetic interest, with ongoing efforts to develop more efficient and scalable manufacturing processes.

 

Product Parameters

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Parameter	Specification
Product Name	Abemaciclib
CAS Number	1231929-97-7
Molecular Formula	C₂₇H₃₂F₂N₈
Molecular Weight	506.59 g/mol
Boiling Point	689.3±65.0 ℃
Density	1.32±0.1 g/cm3
pKa	7.69±0.10
Appearance	White to yellow solid
Storage Condition	4 °C, protect from light

 

Indication

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Abemaciclib is administered in combination with fulvestrant for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer. Verzenio is used alone to treat the same patient population who have undergone endocrine therapy and chemotherapy but developed cancer metastases.

 

Bioactivity

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Abemaciclib (LY2835219) is a cell cycle inhibitor that selectively targets CDK4/6, with IC50 values of 2 nM and 10 nM in cell-free assays, respectively.

 

Synthetic Route

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Under nitrogen protection, nitrogen gas was bubbled for 5 minutes into a solution containing 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzimidazole (5 g, 15.5 mmol), 5-(4-ethylpiperazin-1-yl)methyl)pyridine-2-amine (3.48 g, 15.8 mmol), potassium carbonate (4.71 g, 34.1 mmol), and xanthic acid (179 mg, 0.3 mmol) in tert-butanol (25 mL). Subsequently, tris(2-benzylideneacetone)dipaladium (0) (142 mg, 0.2 mmol) was added, and the reaction mixture was heated to 100°C and stirred for 19 hours until HPLC analysis confirmed complete conversion of the pyrimidinobenzimidazole compound. After completion, the mixture was cooled to room temperature, diluted with dichloromethane according to Chemicalbook guidelines, and filtered through a Whatman glass fiber filter. The filtrate was extracted with a 4N hydrochloric acid aqueous solution (2 × 25 mL); the aqueous phase was collected, activated carbon (250 mg) was added and stirred, followed by filtration (Through Whatman), and the mixture was alkalized with a 17% sodium hydroxide solution (30 mL). The alkalized mixture was then extracted twice with dichloromethane (2 × 20 mL); the organic phase was dried with anhydrous sodium sulfate, filtered, mixed with Quadrasil (800 mg), filtered again, and concentrated under reduced pressure. The remaining crude product was a yellow solid, which was slurryified in acetone, filtered, washed with acetone, and dried under reduced pressure to yield the final fine yellow powder product. Yield: 4.5 g (yield rate 57.3%); Chemical purity: 99.4% (as determined by peak area at λ = 320 nm).

 

Contact Us

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Securing Abemaciclib for your CDK4/6 inhibitor manufacturing campaign or oncology drug development program should be straightforward. Cosperpharm makes it simple.