KBS30-7 - N-alkylation with KBS29

[KlementineJBS]

Link to HIRAC and master page.

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

Notes

Using cesium carbonate as base and THF as solvent.

Reaction scheme

[KlementineJBS]

1. Added 58 mg of SM (0.120 mmol) to a flask
2. Evacuated and backfilled x 5
3. Added dry THF (2 mL) and chilled to 0 C
4. Tried to dissolve KBS29 (77.2 mg, 0.269 mmol, 2.2 equiv.) in dry THF (2 mL) but couldn't get it to dissolve. Ended up transferring contents of flask to the vial containing KBS29 and putting this under nitrogen instead.
5. Added cesium carbonate (246.5 mg, 0.757 mmol, 6 equiv.).
6. Left stirring at rt from 3.50 pm

[KlementineJBS]

LRMS

SM, mono product evident. Some mystery peaks.

Mystery 1+ peaks: 602.10, 639.03
Mystery 1- peaks: 566.91

618.93 [M+Cs]+ of SM

KBS30-7 RM 11-01-24.pdf
KBS30-7 RM 11-01-24.zip

[KlementineJBS]

12.01.24

Quenched with 10 mL ammonium chloride solution at ~4 pm to maintain consistency.

TLC at time of quenching:

solvent system is 4.5% MeOH, 0.5% ammonium hydroxide in DCM

[KlementineJBS]

Worked up with toluene (3 x 10 mL) and a little DCM, washed with water (30 mL) and brine (30 mL). DCM is an easier solvent to use if multiple washes aren't required (as with DMF) but wanted consistency across these screens.

[KlementineJBS]

LRMS

no sign of product.

KBS30-7 cr.pdf
KBS30-7.d.zip

[KlementineJBS]

LRMS take 2

Tiny peak of mono product visible.

KBS30-7 cr 16-01-24.d.zip
KBS30-7 cr 16-01-24.pdf

[KlementineJBS]

Column details

Note that the 10% MeOH in DCM is made using ammonia-saturated methanol (~7 M).

Expected that the lower spots would be product as with #169 but this wasn't the case. None of the fractions appear to contain any linear amines.

Fractions	Tare (g)	Mass (mg)	Substance
1-4	-	-	SM KBS29
10-26	-
27-34	15.
35	15.
36-37
38+

[KlementineJBS]

H NMR

KBS30-7 column.pdf

KBS30-7 F1-4_1.zip
KBS30-7 F10-26_1.zip
KBS30-7 F35_1.zip
KBS30-7 F36-37_1.zip
KBS30-7 F38+_1.zip

[KlementineJBS]

LRMS of F10-26

Again only signs SM and a tiny amount of mono product.

KBS30-7 F10-26.pdf
KBS30-7 F10-26.d.zip