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17th July 2014 @ 03:20

Reaction completed unsuccessfully: instead of desired product, N'-(6-chloropyrazin-2-yl)formohydrazide was formed and isolated.

TM 37-1

 

Attempting to follow the methodology of patent CA2850137.

2-chloro-6-hydrazinylpyrazine (Synthesis of 2-chloro-6-hydrazinylpyrazine (TM 34-1): crude, assume 3.36 mmol) was dissolved in formic acid (5 mL), and triethyl orthoformate (0.57 mL, 3.4 mmol, ~1 eq) added. The reaction mixture was stirred at 100 oC for 20 hours: TLC still showed some remaining starting material, but a workup was performed. The solution was (ineffectually) concentrated under vacuum, then neutralised with sodium bicarbonate solution (this increased the volume to ~25 mL: next time, use NaOH), extracted with EtOAc (4 x 15 mL), washed with water (10 mL) then brine (10 mL), then concentrated under vacuum to give crude TM 37-1 (350 mg). The crude was purified by flash chromatography (10 % EtOH in chloroform), to give pure TM 37-1 (280 mg) as a tank solid.

NMR (1H, DMSO, 200 MHz):

TM 37-1 columnde 1H DMSO 200 MHz.pdf

There are too many signals for this to be the desired product, and so (together with an LCQ-MS spectrum without pdf to upload: [M-H]- 171.07, 173.07; calculated 153, 155), the product obtained appears to be N'-(6-chloropyrazin-2-yl)formohydrazide. This would imply that the reaction pathway favoured under these conditions begins with condensation to formic acid, not the orthoester, but without the desired cyclisation occurring. Thoughts for next time: try hotter conditions (boil off water?); try reaction in neat orthoester, perhaps with catalytic acid.

 

InChI:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

to

InChI=1S/C5H3ClN4/c6-4-1-7-2-5-9-8-3-10(4)5/h1-3H

HIRAC:

HIRAC.pdf
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Attached Files
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HIRAC.pdf
TM 37-1 columnde 1H DMSO 200 MHz.pdf
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