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Topic: Help needed with Imatinib synthesis step.  (Read 3208 times)

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Offline kea1118

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Help needed with Imatinib synthesis step.
« on: March 28, 2017, 09:50:33 PM »
Hi All,

I've been trying to work out the mechanism for the following step in the synthesis of Imatinib. I would greatly appreciate any tips on how the mechanism begins or if there are any sources online that show a reaction mechanism somewhat like this.

Thank you in advance for your help,

Offline wildfyr

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Re: Help needed with Imatinib synthesis step.
« Reply #1 on: March 28, 2017, 10:13:48 PM »
I feel strongly that there are other reagents in this. Or at least a solvent.

Offline phth

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Re: Help needed with Imatinib synthesis step.
« Reply #2 on: March 28, 2017, 11:30:29 PM »
I feel strongly that there are other reagents in this. Or at least a solvent.

Are you sure?  It's an ortho amide, which has a higher transition state than tetrahedral intermediates between immines and aldehdyes. The 2 methoxy anions are the 2 eq of base required to start the reaction.  It seems like one less thing to do if you are already gonna distill the orhto acid dry.

Offline kea1118

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Re: Help needed with Imatinib synthesis step.
« Reply #3 on: March 28, 2017, 11:49:01 PM »
Is the alpha hydrogen acidic enough with just the DMF-DMA to be deprotonated to form the carbanion? That's where I'm getting lost. I got the picture from synthesis pathway Pharmaceutical Substances. There was a mistake in the esomeprazole one so it is possible that maybe a solvent is missing because I don't think the methoxy ion would be a strong enough base to deprotonate the alpha hydrogen.

Offline wildfyr

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Re: Help needed with Imatinib synthesis step.
« Reply #4 on: March 29, 2017, 08:23:42 AM »
Perhaps I am wrong. Methoxy ion should be strong enough to pluck that alpha hydrogen.

Offline sjb

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Re: Help needed with Imatinib synthesis step.
« Reply #5 on: March 29, 2017, 12:22:09 PM »
Perhaps I am wrong. Methoxy ion should be strong enough to pluck that alpha hydrogen.

I'd think so - having carried out work similar to that described in WO2007054254A1 in the past.

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