TCMDC_ArylPyrrole

 

Product obtained in 10% yield.

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Synthesis of the core pyrrole of TCMDC-123794 and TCMDC-123812 from the GSK Tres Cantos antimalarial dataset listed in ChEMBLdb NTD database

Condensation of 4-fluoroaniline and 2,5-hexanedione to form 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole.



Experiment start time 16.10 EST 17/08/2011
4-fluoroaniline (94.7 μL, 1 mmol, 1 equiv.) and 2,5-hexanedione (117.3 μL, 1 mmol, 1 equiv.) were dissolved in ethanol (50% aqueous, 1 mL) in a microwave tube and heated in a CEM Discover microwave. Target temperature 160 °C for 20 minutes (5 minute ramp time). Measured 96 °C, 50 psi. Reaction shows new product by TLC and baseline starting materials. Reaction mixture diluted with water (10 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were then washed with 1M HCl (5 mL), dried (MgSO₄) and concentrated under reduced pressure to obtain a brown oil. The oil was purified by chromatography on base (NEt₃) washed silica (1% NEt₃/petrol) to obtain a thick colourless oil (18 mg, 10%) that turned blue on standing (10 minutes). No mass ions consistant with SM or products were observed by ESI (11.38 EST 18/08/2011). ¹H NMR consistant with product and literature¹

TLC (10% EtOAc/petrol) visualised by UV and vanillin:


Column TLC:


Analytical Data
¹H (200 MHz, CDCl3, TMS) 7.24-7.10 (4H, m), 5.90 (2H, s), 2.02 (6H, s).

¹H NMR Spectra


References:

1. Manetti, F.; Magnani, M.; Castagnolo, D.; Passalacqua, L.; Botta, M.; Corelli, F.; Saddi, M.; Deidda, D; De Logu, A. ChemMedChem, 2006, 1, 973–989. doi: 10.1002/cmdc.200600026
   

Hazard and Risk Assessment: