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17th July 2012 @ 04:27
Desired product synthesised in 79% yield.

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Synthesis of amine linked TCMDC-123812 analogue using conditions employed for PMY 51-2.

PMY38-5.png

Reaction Start Time: 13.40 17/07/12
Glycinamide hydrochloride (132 mg, 1.20 mmol, 1.3 equiv.) was dissolved in water (approx 0.2 mL). Sodium hydroxide (48 mg, 1.20 mmol, 1.3 equiv.) was added and the reaction stirred for 10 minutes, then concentrated under reduced pressure. PMY 2-5 (200 mg, 0.92 mmol, 1 equiv.) was added and the mixture dissolved in MeOH (10 mL) and acetic acid (0.25 mL). 1505: Sodium cyanoborohydride (64 mg, 1.01 mmol, 1.1 equiv.) was added in 3 portions over 3 minutes. Reaction complete by TLC at 18 hours; 2(+) product spots. The mixture was concentrated under reduced pressure then treated with 1M NaOH (10 mL). The mixture was then extracted with DCM (3 × 15 mL). The extracts were washed with brine then dried (MgSO4) and concentrated to an orange solid (247 mg). Purified by chromatography on silica (2-8% MeOH/DCM then NH4OH/MeOH/DCM 3:8:89). Gave PMY 38-5-A (22 mg) consistent with bis-alkylated material and PMY 38-5-B (200 mg, 79%), consistent with desired product.

TLC (5% MeOH/DCM) visualised with UV and vanillin:
TLC 18 hours


NMR:
1H NMR PMY 38-5-B
1H NMR PMY 38-5-A
1H, 13C, 19F NMR PMY 38-5-B


Mass Spec:
PMY 38-5-A: HRMS (ESI+) found 477.24699 [M+H], C28H31N4OF2 requires 477.24604.
PMY 38-5-B: HRMS (ESI+) found 298.13340 [M+Na], C15H18N3OFNa requires 298.13261.

See Also:
Reductive alkylation of glycinamide (PMY 51-2)
Reductive amination of pyrrole aldehyde with crude PMY 53-2 (PMY 56-1)
Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium cyanoborohydride (PMY 38-4)

Risk and Hazard Assessment:
See: Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium cyanoborohydride (PMY 38-4)
Linked Entries
Attached Files
Scheme
TLC 18 hours
1H NMR PMY 38-5-A
1H NMR PMY 38-5-B
1H, 13C, 19F NMR PMY 38-5-B