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15th June 2012 @ 08:04
Conversion of PMY 48-1 to more polar 2-imino-thiazolidin-4-one arylpyrrole compounds by methylation then condensation with amines.

PMY49-1.png

Reaction start time 17.05
Crude PMY 48-1 (502 mg, 1.51 mmol, 1 equiv.) was dissolved in EtOH (30 mL). N,N-diisopropylethylamine (395 μL, 2.27 mmol, 1.5 equiv.) was added followed by iodomethane (478 μL, 7.55 mmol, 5 equiv.). Reaction was stirred for 64 hours, then concentrated under reduced pressure to an orange solid. TLC shows complete reaction. Solid recrystallised from hot methanol (no washes, iodide salts still present most likely. The batch was dissolved in methanol (55 mL), split in 2 portions. The 2 reactions were treated with Ethanolamine (137 μL, 2.27 mmol, 1.50 equiv. PMY 49-1-A) and morpholine (195 μL, 2.27 mmol, 1.50 equiv. PMY 49-1-B) were added and the reactions heated to reflux. After 24 hours, the reactions were cooled to room temperature and concentrated under reduced pressure. The yellow solids were recrystallised from EtOH/water to obtain yellow powders. Yellow powders (PMY 49-1-A, 31 mg) insoluble in CDCl3 and MeOD. Both batches extracted with DCM (4 × 20 mL). The extracts washed with brine (2 × 30 mL), dried (MgSO4) and concentrated under reduced pressure. PMY 49-1-B, orange foam. PMY 49-1-A orange solid. Triturated with Et2O and transferred to vial using DCM, only partially soluble in DCM. Tedious to handle. Light brown solid.

Both dried under vacuum overnight: PMY 49-1-A (134 mg), PMY 49-1-B (253 mg).

TLC (50% EtOAc/hexane) visualised with UV and KMnO4:
TLC intermediate


NMR:
1H NMR intermediate


Risk and Hazard Assessment:
RA
Attached Files
14th June 2012 @ 00:41
Synthesis of the rhodanine derivative of PMY 2-5 for further elaboration to give variation at the imine of 2-iminothiazolidin-4-one.

PMY48-1.png

Experiment Start Time: 0940 12/06/12
Rhodanine (379 mg, 2.84 mmol, 0.95 equiv.) was dissolved in EtOH (20 mL). Piperidine (443 μL, 4.49 mmol, 1.50 equiv.) was added followed by aldehyde PMY 2-5 (650 mg, 2.99 mmol, 1 equiv.). The brown solution was heated to 60 °C. After 7 hours, TLC shows a only a small amount of SM remaining. Reaction allowed to cool to room temperature. After approx. 16 hours, the mixture was cooled in ice. No precipitate formed. Water was added slowly until the mixture became yellow milky and a sticky gum precipitated out. The mixture was extracted with DCM (3 × 25 mL) and washed with brine then dried (MgSO4) and concentrated under reduced pressure to an orange solid (1.36 g). 1H NMR show new product, a small amount of PMY 2-5, piperidine, ethanol and (potential piperidine salts?).

The crude mixture was dissolved in DCM (60 mL) and washed with 1M HCl (2 × 10 mL), 10% NaHCO3 (2 × 10 mL) where upon the mixture became a milky suspension, water (3 × 20 mL), brine then dried (MgSO4) and concentrated under reduced pressure to a yellow solid.

TLC (20% EtOAc/hexanes) visualised with UV and vanillin:
TLC 7 hours


NMR:
1H NMR crude


Reference:
doi: 10.1016/j.bmcl.2011.09.049
doi: 10.1016/j.bmcl.2007.01.081

Risk and Hazard Assessment:
RA
Attached Files