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9th July 2013 @ 02:24

Nucleophilic displacement of the chlorine of MNR 99-3 for 2-dimethylaminoethanol. As effort towards synthesising aminothienopyrimidine analogues discussed in the May 2013 Open Consultation.

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Reaction completed and gave 59 % yield after purification by column chromatography. Product taken forward in to bromination (MJT 16-1).

This is a novel compound; data to be collected: IR, LRMS, HRMS

Procedure

2-dimethylaminoethanol (1.7 mL, 17 mmol, 6.0 equiv.) was added to MNR 99-3 (0.496 g, 2.91 mmol, 1.0 equiv.) to give a yellow solution. This solution was heated to 85oC and left at this temperature with stirring for 3 hours. TLC analysis showed all MNR 99-3 had been consumed and formation of new, more polar product(s). The solution was cooled to room temperature, a white solid precipitated out of solution. Ethyl acetate (2 mL) was added and the reaction mixture was left stirring at room temperature in a sealed vessel for 14 hours. Water (10 mL) was added to the solution and the white solid dissolved. The crude product was extracted with ethyl acetate (3 x 20 mL), the combined extracts were washed with brine (10 mL) and then dried using anhydrous Na2SO4 before concentration under reduced pressure to give a pale yellow oil (0.529 g, 2.4 mmol, 81 %). NMR analysis showed presence of the desired product though it was wet and contained some amine still. The crude product was dissolved in ethyl acetate, washed with water (20 mL) and then brine (20 mL) before drying over anhydrous Na2SOand concentration to give a yellow oil (0.529 g, 2.4 mmol, 81%). NMR analysis after this second wash showed product was contaminated with some impurities - it had extra signals in the aromatic region. The crude product was purified by column chromatography (2%, 5%, 7.5%, 10% methanol in DCM) over silica (40-60 micron particles) to give 2 fractions: the top spot as a white solid (0.03 g) and a bottom spot as a pale yellow oil (0.381 g, 1.7 mmol, 59%); the bottom spot is pure product by NMR.


Hazard and Risk Assessment

MJT 14-1 HIRAC


Data

TLC 

TLC MJT 14-1

H NMR

 after column:

MJT_14-1_purified_by_column.pdf

before column:

MJT 14-1 after second wash.pdf

 

H NMR of MNR 99-3 

H NMR of 2-dimethylaminoethanol

Characterisation Data

1H NMR


MJT 14-1 proton.pdf
MJT 14-1 proton nmr raw data

13C NMR

MJT 14-1 carbon.pdf
MJT 14-1 carbon nmr raw data

Mpt. < RT, MJT 14-1 is an oil

Attached Files
MJT 14-1.png
MJT 14-1 amounts table
MJT 14-1 HIRAC
MJT 14-1 HIRAC
TLC MJT 14-1
MJT 14-1 after second wash.pdf
fid
MJT 14-1 crude after first wash raw nmr data
MJT_14-1_purified_by_column.pdf
MJT 14-1 carbon.pdf
MJT 14-1 proton.pdf
MJT 14-1 proton nmr raw data
MJT 14-1 carbon nmr raw data