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Published synthesis of PD-0332991 (Palbociclib)

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The preferred range of temperature is between 60oC to 90oC (the range is important to keep the enzymatic reaction optimum, bsides, tis range attains the desired speed without altering the expected results), wich is maintained for 10 hours. After the process, te intermediate ester formed undergoes the cyclization process through AcOH and heating. Tis stage involves amino-pyridinyl Coupling. Te stage begins with the halogenation of the compound from the previous stage. Te halogenation process involves taking the compound through several conditions. I involves the addition of bromide compounds.

involves using a suitable solvent and a base. Te heating stage continues for 16 hours while stirring at a temperature between 40oC to 60o C. Example of base include the sodium acetate while solvents such as acetic acids require duration of 35 hours at a temperature of 50oc. Oher bases with a potential for the similar purpose include potassium acetate while the solvents such sdichlroromethane and methanol may also be used ( because they provide optimal medium for the reaction similar to the primary solvent) as alternative to this preferred agents for the halogenation process include the dibromohydantoin, NS, o bromine.

Te step involve using organosilicon compound named lithium bis(trimethylsilyl)amide-LiHMDS, wich act as a ligand. Te ligand reacts with the bromine halide (attached to the comound) through a process called salt metathesis reaction (as shown in the figure 7 below). Te process give rise to a meta trimethylsilyl amide, wich makes the compound lipophilic (because of the effect by the ligand). Te product formed will be soluble in the non polar solvents hence increasing its reactivity. Tis is regioselective Heck Coupling.

Te stage involves using a suitable solvent like n-butanol (because the complex has increased reactivity with n-butanol unlike other non polar solvents), wich is mixed with a base and vinyl ether. Prior to the commencement of heating the mixture, uually at a temperature of 75oC, acatalyst of palladium is added (as shown in figure 8 below). Te process is maintained for about 10 hours while stirring the mixture. Te final stage involve adding isethionic acid and carrying out deprotection. Te process of adding isethionic uses a protocol.

Te whole step last for about 1 hour with optimal results expected after 3.. .

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preview essay on Published synthesis of PD-0332991 (Palbociclib)
  • Pages: 4 (1000 words)
  • Document Type: Essay
  • Subject: Chemistry
  • Level: Undergraduate
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