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26th October 2011 @ 04:42
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Coupling of the acid chloride of PMY 8-2 and 4-aminoantipyrine for a analogue of TCMDC-123794 that does not contain the ester linker. Forming acid chloride to avoid acylurea by-product and to determine if the "anhydride is formed".

Reaction Scheme

Reaction Start Time: 1500 26/10/11
PMY 8-2 in DCM (4 mL) was cooled in an ice bath. 1 drop DMF was added followed by oxalyl chloride (0.05 mL, 0.59 mmol, 2.8 equiv.). After 10 minutes visible evolution of gas had stopped. Reaction allowed to warm to room temperature. After 2 hours, reaction was concentrated under reduced pressure, then redissolved in DCM (4 mL). 4-aminoantipyrine (48 mg, 0.24 mmol, 1.1 equiv.) dissolved in DCM (1 mL) and added to the reaction. After over night reaction, TLC shows disappearance of antipyrine (despite being in excess). Triethylamine (approx 0.5 mL) was added, a solid (NEt3.HCl) forms. Reaction diluted with DCM (10 mL) and washed with water (2 × 10 mL), 10% NaHCO (10 mL), water (2 × 10 mL), brine and dried (MgSO4) and concentrated under reduced pressure to a brown solid (116 mg). Purified by chromatography (0.5-10% MeOH/DCM).
12-2-A, top spot, yellow crystalline solid (26 mg), consistent with PMY 10-1 by 1H NMR.
12-2-B, 3 mixed spots (mid), brown oil.
12-2-C bottom spot (UV only), pale brown crystalline solid (35 mg), not desired product. Appears to be derived from 4-aminoantipyrine, 8.96 ppm (1H, s), 5 × ArH, 12 alkyl H?! DMF adduct?

TLC (10% MeOH/DCM) visualised with UV and vanillin:[b]
TLC
Column TLC


[b]NMR:

1H NMR 12-2-A
1H NMR 12-2-B
1H NMR 12-2-C


Risk and Hazard Assessment:
See: Coupling of acid PMY 8-2 and 4-aminoantipyrine for a linker-less analogue of TCMDC-123794 (PMY 12-1)
Replacing DCC and DMAP for oxalyl chloride (toxic, corrosive).
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Attached Files
Reaction Scheme
TLC
Column TLC
1H NMR 12-2-A
1H NMR 12-2-B
1H NMR 12-2-C