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2nd February 2012 @ 06:30
Target synthesised in 39% yield. Requires 13C, 19F

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Synthesis of the amide analogue of TCMDC-123812 by coupling of glycinamide and preformed acid chloride PMY 32-2.

Reaction Scheme

Reaction start time: 18.00 02/02/12
Glycinamide.HCl (51 mg, 0.51 mmol, 1.2 equiv.) and DIPEA (0.11 mL, 0.89 mmol, 2.3 equiv.) in dry DMF (6 mL). Incomplete solution (even on heating). PMY 32-2 (90 mg, 0.39 mmol, 1 equiv.) was dissolved in dry THF (4 mL) and added to the Glycinamide suspension. Reaction heated to 80 °C. After overnight heating, reaction was cooled to room temperature. After standing over the weekend, the mixture was concentrated under reduced pressure. The residue was purified by chromatography (50-100% EtOAc/hexane then 0-20% MeOH/DCM) to obtain a clear yellow oil (162 mg, 145% of theory!). 1H NMR shows residual DIPEA (salt?) and expected product. After drying under high vacuum overnight, mass still greater than theory (134 mg). White powder dissolved in 10% NaHCO3 (10 mL) and DCM (10 mL, yellow solution) some insoluble powder. Separated and the organic washed with water (3 × 10 mL), brine and dried (MgSO4) and concentrated under reduced pressure to a white powder (44 mg, 39%). Mpt 193-195 °C.

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

DMF interfering with TLC.

NMR:
1H NMR with residual DIPEA
1H NMR, dried under high vac


Mass Spec:
m/z (ESI+) 312 [M+Na]+, 100%
Mass Spec


See also:
Coupling of pyrrole carboxylic acid PMY 8-3 and glycinamide (PMY 31-4)
Synthesis of pyrrole acid chloride of PMY 8-4 (PMY 32-2)

Risk and Hazard Assessment:
Synthesis of TCMDC-123812 via acid chloride (PMY 10-1)
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Attached Files
TLC
1H NMR with residual DIPEA
Mass Spec
1H NMR, dried under high vac