KBS30-5 - N-alkylation with KBS29

[KlementineJBS]

Link to HIRAC and master page.

Previous attempt is #165

KBS30 - Generic alkylation of 1,x-diaminoalkane with naphthalene-triazole pendant (updated).docx

Notes

Using sodium hydride as base instead of potassium carbonate.

Reaction scheme

Outcome

Bis product: 14.1 mg, 0.0157 mmol, 10%
Mono product: 4.6 mg, 0.0066 mol, 4%
Mixed: 13.9 mg (max. 12%)

[KlementineJBS]

12.12.23

1. Added linear amine SM (78.1 mg, 0.161 mmol) to a flask with NaH (14 mg, 0.348 mmol, 2.2 equiv., 60% mineral oil dispersion) and dissolved in dry DMF (2 mL)
2. Backfilled and evacuated x 5
3. Left stirring for ~30 minutes
4. Put on ice and added pendant group KBS29 (100 mg, 0.348 mmol, 2.2 equiv.) dissovled in dry DMF (2 mL). Left stirring from ~ 2.15 pm

TLC consistently indicated that pendant SM was not consumed. A new spot, closer to the baseline than the linear amine SM, formed - it is unknown what this is. Potentially hydrolysis of the KBS29 pendant again.

Reaction was heated to 50 C for ~ 2hrs but this had little effect. Reaction turned off at 5.30 pm.

[KlementineJBS]

14.12.23

Reaction had been left untended due to power outages. Quenched with ammonium chloride solution (10 mL), then worked up with toluene (3 x 25 mL), washed with lithium chloride solution (5%, 2 x 40 mL), water (40 mL) and brine (40 mL).

Note that DCM dissolves the product better than toluene but makes it more difficult to wash.

[KlementineJBS]

Column

Tried columning with a gradient of 1 - 5% ammonia in methanol / in DCM.

[KlementineJBS]

LRMS

Signs of both mono and bis in F2, and of mono, bis and SM in F3-4.

mono = 716+ [M+Na]+, 692- [M-H]-
bis = 923+ [M+Na]+
SM = 485- [M-H]-, 509+ [M+Na]+

KBS30-5 F3-4.pdf
KBS30-5 F2.pdf
KBS30-5 F2, F3-4.zip

[KlementineJBS]

Column e

Fractions	Tare (g)	Mass (mg)	Substance
1-3	-	-	junk
8-57	-	2 mg	not tested
58-65	15.6712	13.9	SM and mono product
66-73	15. 8277	4.6	mono product
92-93	15.6791	14.1	bis product

Solvent system is 2% ammonia-saturated methanol in DCM.

[KlementineJBS]

LRMS

484.76 [M-H]- for SM, 691.91 [M-H]- for mono product

616 match with cesium adducts but these shouldn't be present in this sample.

KBS30-5e 58-73.pdf

923.22 [M+Na]+ of bis product

KBS30-5e 92-95.pdf
KBS30-5e fractions.zip

[KlementineJBS]

H NMR

KBS30-5e fractions.pdf
KBS30-5e 58-65_1.zip
KBS30-5e 92-95_1.zip
KBS30-5e 66-73_1.zip