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UCL Mur Ligase Local Team Meetings December 2021 #60

Open Yuhang-CADD opened 2 years ago

Yuhang-CADD commented 2 years ago

DOE of WYH17-X series

Part 1: Solvent screening

1.1 Tried in a small scale (30 mg SM1, 1.1 eq SM2, 1.0 Na2CO3, 1.0 DIPEA, MW 170℃, 45 min)

image

Conclusion: none of those solvents gave promising improvements to the yield under such conditions. So far, n-BuOH is still the best SNAr solvent for this system.

1.2 Solvent heating variables explored, trying to check if the solvents below could actually reach 170 ℃ under different conditions like vial size, solvent volume, machine settings, etc.

image

Conclusion: n-BuOH cannot reach 170℃ when the vial size is too large (10-20 mL range). And only n-BuOH, DMSO, DMF, and Pyridine can reach the targeting temperature 170℃.

The MW absorption level varies among solvents and the "Absorption Level" setting on Biotage Initiator is about changing the wavelength of supplied energy based on the general MW types of solvents (low, medium, high---from non-polar to polar).

Changing the vial size may cause the change of the "Absorption Level" setting; when increasing the vial size (and correspondingly the solvent volume), the heat take longer time to build up than the previous setting. Thus, changing the "Absorption Level" (e.g. from High to Normal) might give the machine a bit of more flexibility of heating solvents up.

Part 2: Condition modifications

2.1 Having changed the eq of SM2, Na2CO3, and reaction scale

image

Progress: having separated WYH17-1~WYH17-5 from the reverse phase column, obtaining fractions of P (with SM1) and BP. Need further purifications.

Haven't decided what the eq of SM2 should be for the larger scale reaction WYH17-6.

mattodd commented 2 years ago

Hi @ZigBu can I just check that this paper is included somewhere in the wiki, e.g. here? If not, can you please add it in?

ZigBu commented 2 years ago

Hi professor @mattodd: I have already added the compound mentioned in this paper and both cdx. and png. files have been uploaded. I also find this paper (DOI) related and also added that into the wiki. I hope you can check it. If there is any problem, I will correct it immediately.

Many Thanks, Best wishes