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09-06-2016, First step in synthesis of the hetero-oxadiazole, reaction of 2-6 dichloropyrazine with malononitrile, following procedure from Nikishkin et al (2013)
09-11-2016, Work up of the second attempt at step 1
09-23-2016. Step 1 redo, on 5 gram scale
09-24-2016. Work up of 09-23-2016
09-29-2016, work up and purification of [4]
09/28/2016 Step 4, on a larger scale this time. Conversion of methyl 6-chloropyrazine-2-carboxylate [3] to methyl 6-hydrazineylpyrazine-2-carboxylate [4] using hydrazine according to AEW 85-5
10/07/2016 GC mass spec characterization of rxn from [4]->[5]
10/18/16: Trial work up of reaction of 6-chloropyrazinecarbonitrile and hydrazine
10/4/16: Trial of Step 4:Product [4] to Product [5]
10/6/16: Trial Synthesis of 6-hydrazinelypyrazine-2-carbonitrile and from 6- hydrazinelypyrazine-2-carboximidhydrazide from chloropyrazinecarbonitrile
9/12/16 Step 2 in synthesis. Going from [2]->[3]
9/13/16: Work-up of product [3] and TLC plates
9/15/16: Second Synthesis of Methyl 6-chloropyrazine-2-carboxylate [product 3]
9/18/16-9/20/16: Trial Synthesis of Methyl 6-hydrazineylpyrazine-2-carboxylate (Product 4)
9/22/16: Inconclusive Trial Synthesis of Methyl 6-hydrazineylpyrazine-2-carboxylate (Product 4)
9/25/16-9/27/16: Synthesis of Product 3, methyl 6-chloropyrazine-2-carboxylate
9/27/2016 Late Night
9/29/2016 HNMR of product 4, and HNMR of product 4 after D2O exchange 01/10/2016
9/8/16-Continued Synthesis of 2-(6-chloropyrazin-2(1H)-ylidene)malononitrile
CNMR so far
HNMR so far, of all relevant compounds
The Synthetic scheme of Hetero-oxadiazole Synthesis
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29th September 2016 @ 02:29

The synthesis of product 2 was very successful. 4.86 g of product 2 was obtained, which is around a 79% yield. All of the product was dissolved in 285 mL of MeOH in a 500 mL round-bottom flask. 3.05 g of lithium carbonate was added and the solution was stirred for 30 minutes. The mixture was a dark yellow color with sediment forming on the bottom of the flask. After 30 minutes, magnesium monoperoxyphthalate hexahydrate (80% tech., 12.48 g) was added at 0 °C. The resulting mixture turned a brighter yellow color, and was stirred overnight.

The reaction was then filtered by vacuum filtration. The filtrate was dried in vacuo, and then portioned between 120 mL of water and 120 mL of CHCl3. The organic layer was taken and dried over MgSO4.

TLC showed that the reaction of product 2 to 3 had gone to completion; there was a substantial amount of product, but also some slight impurities. Eluent: 1:1 Ethyl acetate and hexane. Lane 1: product 2, Lane 2: cospot, Lane 3: crude product 3. Rf product 3: .563

The crude product 3 was a yellow oil. On 9/27/16 it was dry-transferred (DCM, silica gel) to an automated silica column (Biotage), and eluted in a mixture of ethyl acetate and hexane. Fractions were pooled based on UV signal, but have not yet been characterized. 

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