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3rd February 2012 @ 02:41
Target synthesised in 67% yield over 2 steps. Needs 13C, 19F === Coupling of acid chloride of PMY 8-4 and glycinamide derivative PMY 30-3 (crude) to access the amide analogue of TCMDC-123794. [b]Reaction start time: 10.40 03/02/12[/b] PMY 8-4 (178 mg, 0.76 mmol, 1 equiv.) was stirred in dry PhMe (4 mL) and cooled in ice. Thionyl chloride (100 μL, 1.38 mmol, 1.8 equiv.) was added followed by DMF (20 μL). The reaction was allowed to warm to room temperature. After 3.5 hours, reaction was concentrated under reduced pressure twice from PhMe (3 mL). Triturated with hexane (4 mL), filtered (syringe filter) and concentrated to a yellow solid. The acid chloride was dissolved in dry THF (4 mL). Crude PMY 30-3 was stirred in dry THF (4 mL) and DIPEA (0.99 mL, 7.63 mmol, 10 equiv.) was added. After stirring for 5 minutes, the acid chloride solution was added and the reaction heated to 80 °C. After 20 hours, the reaction was cooled to room temperature and left under a nitrogen atmosphere. TLC shows reaction complete. After 2 days, the reaction was concentrated under reduced pressure to an orange oil. Oil crystallised when attempting to load onto silica column. Adsorbed onto silica and purified by chromatography (50-100% EtOAc/hexane, then 5% MeOH/DCM) to obtain an orange oil that solidified on standing (1.25 g). The oil was dissolved in DCM (10 mL) and washed with 10% NaHCO3 (10 mL), water (3 × 10 mL) and brine then dried (MgSO4) and concentrated under reduced pressure to a yellow solid (170 mg, 70% of theory), consistent with a mixture of expected product and DIPEA by 1H NMR. After further drying under high vacuum, 1H NMR is free of DIPEA (162 mg, 67% over 2 steps based on PMY 30-3). [b]TLC (10% MeOH/DCM) visualised with UV and vanillin:[/b] [data]1538[/data] [b]NMR:[/b] [data]1542[/data][data]1566[/data] [b]Mass Spec:[/b] [i]m/z[/i] (ESI+) 498 [M+Na]+, 100%. [data]1568[/data] [b]See also:[/b] [blog]1819[/blog] [blog]1795[/blog] [blog]1792[/blog] [b]Risk and Hazard Assessment:[/b] See: [blog]499[/blog]
Attached Files
Scheme
TLC 20 hours
1H NMR with residual DIPEA
1H NMR, dried under high vac
Mass Spec