The Synthetic Routes of Velpatasvir

Velpatasvir is an anti-viral drug that is used to treat hepatitis B virus (HBV) infections.
It is a nucleotide analog inhibitor, which means it prevents the viral DNA from replicating.
The synthetic route of Velpatasvir involves several steps, each of which is designed to build the molecule gradually until the final product is obtained.

The synthetic route of Velpatasvir can be broadly divided into six stages: (1) starting material selection, (2) route optimization, (3) intermediate synthesis, (4) final synthesis, (5) characterization, and (6) scale-up.

1. Starting Material Selection:

The synthesis of Velpatasvir begins with the selection of an appropriate starting material.
In this case, the starting material is 2',3'-dideoxy-2',3'-dihydro-c-acyclonucleoside (V3DP).
This material is a precursor to the key intermediate in the synthesis of Velpatasvir, which is 2',3'-dideoxy-2',3'-dihydro-c-cytidine (V2DP).

2. Route Optimization:

Route optimization involves the selection of the best method for synthesizing the target molecule.
This step is critical because it can impact the yield, cost, and scalability of the final product.
In the case of Velpatasvir, the route optimization involved testing different reagents and conditions to determine the best method for converting V3DP to V2DP.

3. Intermediate Synthesis:

Intermediate synthesis is the process of synthesizing the key intermediates required for the synthesis of the final product.
In the case of Velpatasvir, V2DP is a critical intermediate, which is synthesized using a P2P reaction.
The P2P reaction involves the condensation of phenyl-2-propanone (P2P) with 3-iodo-2',3':5',6'-tetrahydro-2H-pyrano[2,3-d]pyrimidin-4-one (IHP) in the presence of a base such as sodium hydroxide.

4. Final Synthesis:

The final synthesis involves the synthesis of Velpatasvir itself.
This is achieved by condensing V2DP with 3-(2,4-dioxo-3,4-dihydro-2H-pyrano[2,3-d]pyrimidin-5-yloxy)benzenesulfonic acid (Tristetraprolinamide) in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC) and hydroxy benzene (HBZ).

5. Characterization:

Characterization is an important step in the synthesis of Velpatasvir.
It involves the determination of the physical and chemical properties of the final product, such as its molecular weight, purity, and stability.
This step is critical for ensuring that the final product meets the quality standards required for use as a pharmaceutical.

6. Scale-Up:

Scale-up involves the synthesis of Velpatasvir on a larger scale, typically in the range of tens of kilograms.
This step is critical for ensuring that the synthesis can be scaled up to meet commercial demand.
Scale-up requires careful attention to the optimisation of reaction conditions, the selection of appropriate reagents, and the use of appropriate equipment.

In conclusion, the synthetic route of Velpatasvir involves several steps that are designed to build the molecule gradually until the final product is obtained.
The starting material selection is critical, as is the choice of optimal reaction conditions and the use of appropriate equipment.
The final product must meet quality standards and be scalable to meet commercial demand.
With careful attention to each step in the synthetic route, it is possible to synthesize high-quality Velpatasvir in the chemical industry.