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Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufacture of GDC-0084

SiliaMetS Thiol and Thiourea both outperform activated carbon (Darco) and polymer-based scavengers (Quadrapure) in the palladium scavenging from a drug candidate.

An improved route was designed to synthesize kg-scale quantities of GDC-0084, a drug candidate which showed promising results in the treatment of various brain cancers. The new route was plagued by a high level of palladium contamination (2400 ppm) leftover from a Suzuki cross-coupling. Using either SiliaMetS Thiol or Thiourea, a very low concentration (≤ 16 ppm) could be reached, much lower than what Darco or Quadrapure could achieve. A second generation route used 10 wt.% of a mixture of Si-Thiol and Si-Thiourea to reach 10 ppm of Pd on 7.7 kg scale.

Keywords:
palladium scavenging, metal removal, scavengers, SiliaMetS, activated carbon

> SiliCycle Scavenging Solutions

> SiliaMetS Thiol
> SiliaMetS Thiourea

 

Publication Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufacture of GDC-0084
Authors Andreas Stumpf, Andrew McClory, Herbert Yajima, Nathaniel Segraves, Remy Angelaud and Francis Gosselin
Organization Genentech Inc, South San Francisco, CA (USA)
Source Org. Process Res. Dev. 10.1021 / acs.oprd.6b00011
Date 2016
Reaction scheme Palladium Scavenging by SiliCycle's SiliaMetS Thiol in the Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufacture of a Drug Candidate for the Treatment of Brain Cancer
Full publication http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00011

 

SiliaMetS Metal Scavengers


SiliaMetS Metal Scavengers are functionalized silica gels designed to react and bind excess metal complexes.

Silica-based metal scavengers have been proven to be the purification method of choice over all other methods and several companies from various industries use them.
With the silica matrix advantages over polymers (no swelling, more general solvent compatibility, higher mechanical and thermal stabilities, applications easily scalables and products available in different formats (SPE, flash cartridges and bulk), etc.) combined to SiliCycle’ expertise in grafting technology, SiliaMetS are the solution for metal removal without contamination of drug candidates
SiliaMetS are highly selective and offer a cost-effective alternative for metal scavenging.

SiliaMetS Thiol

SiliCycle Metal Scavenger - SiliaMetS Thiol

SiliaMetS Thiol (Si-Thiol) is a robust metal scavenger for a variety of metals including Pd, Pt, Cu, Ag and Pb under a wide range of conditions. It has been used in pharmaceutical processes up to the pilot plant scale. It is our most versatile metal scavenger and is the preferred metal scavenger for Pd(II), Cu, Ag, and Hg.

SiliaMetS Thiourea

SiliCycle Metal Scavenger - SiliaMetS Thiourea

SiliaMetS Thiourea (Si-THU) is a versatile metal scavenger for all forms of palladium and is widely used in the pharmaceutical industry. It works particularly well in organic solvents. It can also be used to scavenge Ag, Pt, Ru, Rh and Hg. Once complexed with a transition metal, it has been reported as being an effective catalyst.

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