Amino-thienopyrimidine Series

This experiment is designed to test the following conditions for substitution at the 4-amine, on the thienopyrimidine core. Tosyl chloride will be used as a substituent. Thienopyrimidines with tosyl groups on the 4-amine have been tested previously, but none bearing the m-sulfamoylbenzene group at the 4-position. Thus, this experiment is not only a proof of methodology to acheive substitution at the 4-position, but it shall also generate a useful analogue.

Conclusion: Desired product looks to probably have been made (trace yield)

Experiment start time: 10:50 am, 11/12/2012JRC 40-1 (114 mg, 0.5 mmol, 1 eq), tosyl chloride (120.3 mg, 0.63 mmol, 1.3 eq) and DMAP (8.6 mg, 14 mol %) were dissolved in chloroform (5 mL) and stirred at rt. To the stirring solution was added DIPEA (0.35 mL, 2 mmol, 4 eq). The flask containing the resultant solution did not feel warmer to touch. The solution was stirred at rt for 2 hr. TLC analysis showed no significant change. Reaction therefore heated to reflux for 48 hr. No TLC comparison to SM's possible since none remains. Four spots by TLC (10% MeOH/DCM): rf 0.1, rf 0.5, rf 0.55m rf 1.

Reaction allowed to cool to rt. EtOAc (100 mL) added to the solution. Organic layer extracted with H2O (2 x 50 mL) and brine (50 mL) before being dried over MgSO4, and concentrated in vacuoto yield 148 mg product as a maroon solid.

This solid was purified via flash chromatorgaphy (10% EtOAc/hexane -> 100% EtOAc) to yield two aromatic products:

f1: 4 mg\

f2: 42 mg

NOTE: NMR files mistakenly named as JRC 54-1, JRC 54-1F1, and JRC 54-1F2

the first fraction looks to be the desired product by NMR (0.013 mmol, trace). this fraction was mistakenly thrown away.