KBS22-3 - Linear click coupling of bis-propargyl diaminohexane and azidoadamantane

[KlementineJBS]

Link to HIRAC, original method and previous attempt #29

KBS22 Linear amine click coupling with azidoadamantane.docx

Reaction scheme

Outcome

[KlementineJBS]

06.05.24

1. Added 1-azidoadamantane (89.1 mg, 0.503 mmol, 1.3 equiv.), sodium ascorbate (42.9 mg, 0.6 equiv.) and copper sulfate pentahydrate (24.6 mg, 0.0989 mol, 0.3 equiv.) to an RBF
2. evacuated and backfilled with N2 x 3
3. Added KBS22-2 crude product (204 mg, 0.387 mmol assuming all mass is mono-clicked product) dissolved in dry, sparged THF (4 mL)
4. Added sparged water (4 mL)
5. left stirring at rt from 12.30 pm

[KlementineJBS]

added another 26 mg sodium ascorbate at 4.30 pm after TLC indicated reaction was not complete

[KlementineJBS]

07.05.24

Added more copper sulfate (62 mg) as reaction was green in colour. Took a crude NMR which suggested that reaction is almost complete - compare to previous crude mixture.

KBS22-3 RM.pdf nmr300_20240507_KBS22-3 RM_1.zip

[KlementineJBS]

08.05.24

Worked up today.

• quenched with 20 mL ammonium chloride soln (sat.)
• extracted with DCM, 3 x 20 mL
• washed with EDTA (25 mM, 20 mL)
• washed with 40 mL brine and dried over mag sulphate

vial: 15.9973 mass: 235.8 mg (0.316 mmol, 82%)

[KlementineJBS]

H NMR

Some solvent peaks (DCM) but mostly clean. Some signs of mono-clicked compound remaining - seems like maybe 1:2 ratio of mono:bis ?

Need to decide whether to column now or deprotect then column.

NEO500-20240508-15_KBS22-3 cr_1.zip KBS22-3 cr.pdf

[KlementineJBS]

09.05.24

Attempted a multiple silica plug purification. Used about 4-5 cm silica.

1: 100 mL of 10% MeOH in DCM 2: 50 mL methanol 3: 100 mL methanol 4: silica flush (methanol)

[KlementineJBS]

H NMR

Seems like this hasn't really worked as an effective way to clean up sample. Will TLC to confirm then perhaps pool and column normally.

KBS22-3 silica plug.pdf nmr300_20240509_KBS22-3 SP1_1.zip nmr300_20240509_KBS22-3 SP3_1.zip nmr300_20240509_KBS22-3 SP2_1.zip

[KlementineJBS]

Pooled in vial SP1 (tare weight 16.1024 g)