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30th June 2016 @ 02:51

GitHub Issue #400 Resynthesised as part of "Frontrunner" campaign.

(218 mg, 0.051 mmol, 44% yield)

Starting material synthesis: Synthesis of 5-chloro-3-(6-(trifluoromethyl)pyridin-3-yl)-[1,2,4]triazolo[4,3-a]pyrazine (AEW 227-2) 

Procedure:

AEW 227-2 (350 mg, 1.17 mmol, 1 equiv.), potassium hydroxide (229 mg, 4.09 mmol, 3.5 equiv.) and 18-crown-6 (21.6 mg, 81.8 μmol, 0.07 equiv.) were stirred in toluene (11 mL) and 2-(3,4-difluorophenyl)ethanol (185 mg, 1.17 mmol, 1 equiv.) was added and the reaction mixture stirred at rt for 30 mins. TLC showed reaction complete (9:1 EtOAc/hex)


Water (20 mL) was added and the mixture was extracted with EtOAc (3 x 40 mL). Combined organic layers were washed with water (20 mL), brine (20 mL), dried (MgSO4) filtered and evaporated to give a pale yellow solid which was purified by flash column chromatography using the Biotage IsoleraTM with handpacked 50 g column and EtOAc gradient. One fraction collected and evaporated to yield the desired product as a pearlescent cream solid (218 mg, 0.051 mmol, 44% yield).

Screen Shot 2016-07-06 at 4.43.20 PM.png

Data:

200 MHz NMR confirms product + purity, more analysis required.

Screen Shot 2016-07-06 at 4.37.47 PM.png
AEW 296-1 200 MHz.png
aew 296-1_frac.pdf


Hazard and Risk Assessment:

HIRAC AEW 296-1 .doc

Strings:

ClC1=CN=CC2=NN=C(C3=CN=C(C(F)(F)F)C=C3)N21

to

FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4=CN=C(C(F)(F)F)C=C4)N32)=C1

InChI=1S/C11H5ClF3N5/c12-8-4-16-5-9-18-19-10(20(8)9)6-1-2-7(17-3-6)11(13,14)15/h1-5H

to

InChI=1S/C19H12F5N5O/c20-13-3-1-11(7-14(13)21)5-6-30-17-10-25-9-16-27-28-18(29(16)17)12-2-4-15(26-8-12)19(22,23)24/h1-4,7-10H,5-6H2


Attached Files