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6th December 2011 @ 05:19
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Coupling of acid PMY 8-3 and 4-aminoantipyrine for a analogue of TCMDC-123794 that does not contain the ester linker. Using T3P as coupling reagent.

Reaction Scheme

Reaction start time: approx 1600 07/12/11
PMY 8-3 (50 mg, 0.21 mmol, 1 equiv.), 4-aminoantipyrine (48 mg, 0.24 mmol, 1.1 equiv.) were dissolved in EtOAc (approx. 1 mL) and pyridine (0.1 mL, 1.3 mmol, 6 equiv.) and cooled in salt/ice. T3P 50% in EtOAc (0.26 mL, 0.43 mmol, 2 equiv.) was added and the reaction allowed to warm to room temperature overnight. 0.5M HCl (4 mL) and EtOAc (4 mL) were added and the mixture stirred for 30 minutes. The layers separated and the organic layer washed with further 0.5M HCl (5 mL) then 5% NaOH (2 × 10 mL), water (3 × 5 mL), brine then dried (MgSO4) and concentrated. Mass spec consistent with expected product. Product to be purified by chromatography. Chromatography (0-10% MeOH/DCM) gave slightly cleaner material by NMR, gradient too steep, use circa 3% MeOH/DCM isocratic next time. Reaction to be repeated on larger scale, possibly elevated reaction temperature.

TLC (10% MeOH/DCM) visualised UV and vanillin:
TLC after quench


NMR:
1H NMR post washes


Mass Spec:
m/z (ESI+) 419 [M+H]+, 38%, 441 [M+Na]+, 100%.

Risk and Hazard Assessment:
See Synthesis of TCMDC-123794 Side-chain (PMY 5-1) and Synthesis of TCMDC-123812 using T3P (PMY 10-4)

See also:
Coupling of acid PMY 8-2 and 4-aminoantipyrine using EDC for a linker-less analogue of TCMDC-123794 (PMY 12-3)
Coupling of acid PMY 8-2 and 4-aminoantipyrine for a linker-less analogue of TCMDC-123794 (PMY 12-2)
Coupling of acid PMY 8-2 and 4-aminoantipyrine for a linker-less analogue of TCMDC-123794 (PMY 12-1)
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Attached Files
Reaction Scheme
1H NMR post washes
TLC after quench
1H NMR after column