TCMDC_ArylPyrrole

 

Synthesis of the amide analogue of TCMDC-123812 by coupling of glycinamide and acid PMY 8-3.



Reaction start time: 1630 06/01/12
Glycinamide.HCl (78 mg, 0.71 mmol, 1.1 equiv.) were dissolved in EtOAc (approx. 3 mL) and pyridine (0.3 mL, 3.9 mmol, 6 equiv.) and DMF (3 mL). PMY 8-3 (150 mg, 0.63 mmol, 1 equiv.) was added followed by T3P 50% in EtOAc (0.80 mL, 1.26 mmol, 2 equiv.) was added. Glycinamide did not dissolve upon sonication. 0900 09/01/12 Glycinamide appears to have dissolved. 1000 10/01/12 0.5 M HCl (20 mL) and EtOAc (20 mL) added. The layers were separated and the aqueous extracted with further EtOAc (2 × 20 mL). The organic extracts were combined and washed with water (3 × 20 mL) and brine then dried (MgSO₄) and concentrated under reduced pressure. ¹H NMR shows SM acid, trace of a new product and residual DMF. Reaction to be repeated at a higher temperature. Crude material dissolved in EtOAc (approx 20 mL) and washed with 10% NaHCO₃ (3 × 10 mL) and brine then dried (MgSO₄) and concentrated under reduced pressure. The residue (26 mg) was purified by chromatography (3% MeOH/DCM) to obtain two fractions (trace masses), neither of which is consistent with expected product by ¹H NMR.

NMR:


Risk and Hazard Assessment:
See: Synthesis of TCMDC-123812 using T3P (PMY 10-4)