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11th October 2012 @ 02:49
Product obtained according to 1H NMR evidence. Low yield due to inefficient extraction and losses on DMSO NMR samples. Further characterisation data to be collected.

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Synthesis des-methyl pyrazole analogue of TCMDC-123812 using method developed by Alice Williamson.

PMY66-1.png

Reaction Start Time: 15.55 11/10/12
PMY 65-1 (83 mg, 0.35 mmol, 1 equiv.)[calculation error: should be 0.40 mmol] was dissolved in DMF (2 mL) at room temperature. 2-Bromoacetamide (59 mg, 0.43 mmol, 1.2[1.1] equiv.) was added followed by potassium carbonate (98 mg, 0.71 mmol, 2[1.8] equiv.). TLC at 40 mins shows SM and potential product under DMF peak. Not conclusive from initial TLC. Reaction stirred overnight. Partionioned with water and EtOAc (10 mL 1:1). Extracted with EtOAc (3 × 10 mL). Combined organic layers were washed with water (2 × 10 mL), brine and dried (MgSO4) concentrated under reduced pressure and high vacuum to a white solid (36 mg). Crude 1H NMR consistent with expected product and unreacted 2-bromoacetamide (approx 1.1:1 product:acetamide). Aqueous/DMF layer re-extracted using DCM (4 × 10 mL).

Solid recrystallised from hot methanol (approx 4 mL) to obtain colourless needles (10 mg, 9% yield after losses from DMSO NMR samples and recryst). 1H NMR consistent with expected product, clean except very minor impurity doublet at 3.17 ppm. LC/MS shows clean product (264 [M+H]+)

Mpt. 220-221 °C (MeOH)

NMR:
1H NMR crude
1H NMR recrystallised


Sample submitted for service NMR.

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 40 min


LC/MS:
LC/MS after recryst

0to100ov30 MNR method

See also:
Ester synthesis (AEW 5-3)
Hydrolysis of PMY 64-1 ethyl ester (PMY 65-1)

Risk and Hazard Assessment:
As for: Synthesis of ether-linked analogue of TCMDC-123812 (PMY 37-1) except the safer base, potassium carbonate and dimethylformamide as solvent (flammable, harmful in contact with skin or inhaled, eye irritant, may damage unborn child).
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Attached Files
Scheme
TLC 40 min
1H NMR crude
1H NMR recrystallised
LC/MS after recryst