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22nd July 2013 @ 07:35

Coupling of Synthesis of 6-bromo-N,N-dimethylthieno[3,2-d]pyrimidin-4-amine (MJT 10-1) with ortho-sulfonamide boronic acid ester, MNR 103-1. Following methods used by Althea: 90oC for 30 minutes in a microwave reactor (200 W). This is the final stage of the synthesis of one of the aminothienopyrimidine analogues discussed in the May 2013 Open Consultation (see 1b).

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MJT 17-1 was synthesised in 47 % yield.

This is a novel compound, data to be collected: Carbon NMR in DMSO, IR, LRMS, HRMS

Procedure

 A solution of MJT 10-1 (29.5 mg, 0.114 mmol, 1 equiv.), MNR 103-1 (43.0 mg,  0.152 mmol, 1.3 equiv.) and PdCl2dppf (17.0 mg, 0.0232 mmol, 0.20 equiv.) in isopropanol (2.3 mL) and K2CO3 (1 M,  0.23 mL, 0.23 mmol, 2.0 equiv.) was degassed with argon for 10 minutes (see photo MJT17-1A). The reaction mixture was heated at 90oC for 30 minutes in a microwave reactor (200 W). It is now a black solution (see photo MJT17-1B)

The reaction mixture was diluted with MeOH (50 mL) and filtered through celite. The resulting solution was concentrated to a brown solid (0.116 g, 0.347 mmol, >100 %). TLC showed no SM remained and several new products had formed. NMR of this crude product was taken though it was incorrectly calibrated to CDCl3 solvent, and so the peaks occur at the wrong chemical shift values. Correct aromatic peak pattern can be interpreted inferring correct product was made.

Column chromatography (4.5 % MeOH, 0.5 % NH3, 95 % DCM) was used to purify the product and gave one mixed fraction as a brown solid (0.0346 g, 0.10 mmol, 91 %) and one pure fraction as a brown solid (0.005 g, 0.01 mmol, 13 %). It was decided to purify by column again in an attempt to obtain the pure product.

Column chromatography (2.5 % MeOH, 0.5 % NH3, 97 % DCM) was used to purify the combined pure and mixed fractions from the previous column and gave one fraction as a brown solid (0.018 mg, 0.054 mmol, 47 %)

 

Hazard and Risk Assessment

HIRAC MJT 17-1.pdf

Data

TLC

TLC MJT 17-1.JPG

NMR

Crude

MJT_17-1_crude.pdf

Comparable to AT 11-4 NMR - the signals in aromatic region match up


Photos


MJT17-1A

IMG_2161.JPG
 

MJT 17-1B

 

MJT 17-1 post reaction.JPG

Characterisation Data

1H NMR

MJT17-1 pure.pdf
MJT 17-1 raw data H NMR

Mpt. decomposition to black solid at 245-250 ˚C

Linked Posts
Attached Files
Reaction Scheme MJT 17-1.png
HIRAC MJT 17-1.pdf
IMG_2161.JPG
MJT_17-1_crude.pdf
TLC MJT 17-1.JPG
MJT 17-1 post reaction.JPG
Amounts table MJT 17-1.PNG
MJT17-1 pure.pdf
MJT 17-1 raw data H NMR