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12th February 2014 @ 02:53

T3P was used as a coupling reagent, and after column purification final yield was 71 % (0.635 g).

TM 3-1 scheme

 

Procedure: 

6-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol, 1 eq), 3-chloro-2-methylaniline (450 mg, 1 eq), and DIPEA (1.65 mL, 3 eq) were dissolved in DMF (3.2 mL) and cooled to 0 oC on ice. T3P (50% in EtOAc, 4 mL, 2 eq) was added dropwise with stirring, the reaction mixture kept at 0 oC for 15 minutes, then stirred overnight at room temperature. After 18 h, the reaction was judged complete by TLC by the disappearance of the carboxylic acid:

rxn TLC.jpg

(6:1 hexane EtOAc)

 

The reaction mixture was diluted with EtOAc (12 mL), then washed with NaHCO3 (3 x 6 mL). The aqeuous portions were combined and extracted with EtOAc (2 x 12 mL), and the combined organic layers were washed with water (1 x 6 mL) and brine (1 x 6 mL) before being dried over MgSO4. The solvent was removed under vacuum, yielding crude product as fine pale pink crystals. The product was suspended in cold petroleum ether, filtered, and washed with more cold petroleum ether.

After drying on the high vac, yield was 0.785 g (2.79 mmol, 89%) of crude product.

PRODUCT.jpg

The crude product was purified by column chromatography eluted by 1:7 EtOAc:petroleum ether, giving pure TM 3-1 as fine beige crystals after solvent evaporation. The pink colouring observed earlier seemed very polar, barely moving down the column.

Yield: 0.635 g, 2.23 mmol, 71%.

 

Data:

200 MHz CDCl3 1H spectrum (prior to drying under high vacu, unlabelled peaks are remaining EtOAc and DMF)

TM 3-1 crude CDCl3 200 MHz.pdf

 

300 MHz CDCl3 1

1H CDCl3 300 MHz.pdf

300 MHz CDCl3 13

13C CDCl3 300 MHz.pdf

TM 3-1 PURElong.zip

INCHIs:

From:

InChI=1S/C5H3ClN2O2/c6-4-2-7-1-3(8-4)5(9)10/h1-2H,(H,9,10)

InChI=1S/C7H8ClN/c1-5-6(8)3-2-4-7(5)9/h2-4H,9H2,1H3

To:

InChI=1S/C12H9Cl2N3O/c1-7-8(13)3-2-4-9(7)17-12(18)10-5-15-6-11(14)16-10/h2-6H,1H3,(H,17,18)

HIRAC:

HIRAC.pdf

Linked Posts
Attached Files
scheme 3-1.png
HIRAC.pdf
rxn TLC.jpg
TM 3-1 crude CDCl3 200 MHz.pdf
PRODUCT.jpg
1H CDCl3 300 MHz.pdf
13C CDCl3 300 MHz.pdf
TM 3-1 PURElong.zip
Comments
Re: 6-chloro-N-(3-chloro-2-methylphenyl)pyrazine-2-carboxamide (3-chloro-2-methylaniline amide) by Alice Williamson
12th February 2014 @ 05:23
HIRAC seen, slightly more detail on procedures is required.