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7th May 2014 @ 03:06

Repeat of JU 1-5 for synthesis of key starting material.

Reaction Scheme

Procedure

Started 6pm

2,6-Dichloropyrazine (Aldrich, ~5 g, 34 mmol) was dissolved in ethanol (55 mL) to give a clear solution. The exact quantity is unknown as ethanol was used to wash out the remianing amount in the bottom of the container. Hydrazine hydrate (1.85 mL, 1.9 g, 38 mmol) was added resulting in a pale yellow solution. The resulting mixture was heated at reflux (bath temperature 80˚C) for 15.5 h. Analysis by TLC indicated the reaction was complete. 

TLC JU 1-6 30:70 EtOAc:Hex 15.5 h.jpg

The reaction was was cooled to room temperature and the solvent removed by rotary evaporation and the crude product dried in vacuo. The crude product (6.42 g, >100% yield) was analysed by 1H NMR.

1H NMR, crude, DMSO, 200 MHz

JU 1-6 crude DMSO 200 MHz.pdf
JU 1-6 crude DMSO.zip

The crude NMR showed a substantial amount of starting material left (peak at 8.86 ppm). The reaction was re-started at 3:45pm on 8/5/14 using ethanol (50 mL) and hydrazine hydrate (1.6 mL, 1.6g, 32 mmol). The resulting mixture was heated at reflux (bath temperature 80˚C) for 20 h. Analysis by TLC again showed completion. Note that the third spot that has appeared is likely to be excess hydrazine hydrate.

TLC JU 1-6 30:70 EtOAc:Hex 20 h.jpg

The reaction was was cooled to room temperature and the solvent removed by rotary evaporation and the crude product dried in vacuo. The crude product (7.04 g, >100% yield, pale yellow crystals) was analysed by 1H NMR.

1H NMR, crude, DMSO, 300 MHz

JU 1-6 crude DMSO 2 300 MHz.pdf
JU 1-6 crude DMSO 2.zip

A small amount of starting material is still present, however this seems to be in similar quantities to previous attempts which were carried through to the next step.

IR

JU 1-6.pdf


HIRAC & Risk Assessment

See JU 1-1

InChI strings

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

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

SMILES

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(NN)=N1


Linked Posts
Attached Files
Reaction Scheme JU 1-3.png
TLC JU 1-6 30:70 EtOAc:Hex 15.5 h.jpg
JU 1-6 crude DMSO 200 MHz.pdf
JU 1-6 crude DMSO.zip
TLC JU 1-6 30:70 EtOAc:Hex 20 h.jpg
JU 1-6 crude DMSO 2 300 MHz.pdf
JU 1-6 crude DMSO 2.zip
JU 1-6 crude DMSO 2.zip
JU 1-6 crude DMSO 2 300 MHz.pdf
JU 1-6.pdf
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