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18th July 2013 @ 00:41

Bromination of MJT 7-2, using same process as MJT 9-2 but with fewer (2.0) equivalents of n-BuLi. This reduced number of equivalents of n-BuLi was used to attempt deprotonation more selectively at the N-6 position (cf MJT 9-2 which used 2.5 eq and yielded a mixture of 2 regioisomeric products that were brominated at N-6 and N-7). This is an effort towards synthesising aminothienopyrimidine analogues discussed in the May 2013 Open Consultation.


A mixture (27 % yield; 54 % considering amount SM recovered) of the desired product and the product brominated at the other carbon of the thiene bond was isolated but these two compounds were not separated. 50 % of SM was recovered.


MJT 7-2 (0.148 g, 0.900 mmol, 1.0 equiv.) was dissolved in THF (18 mL) under an atmosphere of argon and cooled to -78 °C over 10 minutes. To the stirring solution was added n-BuLi (2.5 M in hexane, 0.72 mL, 1.8 mmol, 2.0 equiv.) and the stirring was continued for 30 minutes. Bromine (0.10 mL, 1.8 mmol, 2.0 equiv.) was added dropwise and the reaction mixture was allowed to reach room temperature and was stirred for 3.5 hours, it is now an orange solution. TLC  at 1h shows some SM remains and some new product spots. TLC at 3.25 hours again shows SM remains and new product spots. The reaction mixture was quenched after 3.5 hours stirring with a saturated sodium thiosulphate solution (50 mL). From this, product was extracted with ethyl acetate (3 x 25 mL). The combined organic extract was washed with brine (25 mL), dried with MgSO4and concentrated to a brown oil (0.170 g, 0.70 mmol, "78%"). NMR analysis of this crude product showed that it contained SM as well as both monobrominated product isomers.

TLC shows that the aqueous washings contain SM and no product; TLC of aqueous extract basified to pH 12 shows it contains SM and a spot on the baseline.

Column chromatography (50 %, 80 % EtOAc in hexane; 40 - 60 micron silica particles) was conducted to give mixed monobrominated products (0.067 g, 0.27 mmol, 27 %) and recovered SM (0.075 g, 0.45 mmol, 50 % recovery).

Hazard and Risk Assessment

HIRAC MJT 9-2.pdf



TLC after 1 h and after 3.25 h

TLC 1h and 3.25 h.JPG

TLC of organic extract and aqueous layer

TLC of organic extract and aqueous layer.JPG


crude product:

MJT 9-3 crude.pdf

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Attached Files
HIRAC MJT 9-2.pdf
MJT 9-3 crude.pdf
MJT 9-3 reaction scheme.png
MJT 9-3 amoun ts table.PNG
TLC 1h and 3.25 h.JPG
TLC of organic extract and aqueous layer.JPG
TLC 1h and 3.25 h.JPG