Triazolopyrazine Series

Crude AEW 232-1  was stirred at room temperature in 4M HCl in dioxane (0.05 mL) for x h

Reaction was quenched with a saturated solution of sodium hydrogen carbonate (2 mL), and then extracted into EtOAc (2 x 10 mL). Combined organic layers were washed with water (5 mL), brine (5 mL) and then dried (MgSO₄), filtered and evaporated.

Adsorbed onto silica and purified using the Biotage Isolera (25g , Hexane/EtOAc - see report) to yield a fluffy yellow solid (28 mg, 0.07 mmol, 20% yield over two steps). NMR looks good but contains solvent impurity - dried further.

Data:

Hazard and Risk Assessment:

Strings:

InChI=1S/C25H24F2N4O4/c26-25(27)34-19-11-9-18(10-12-19)24-30-29-21-14-28-15-22(31(21)24)33-16-20(17-6-2-1-3-7-17)35-23-8-4-5-13-32-23/h1-3,6-7,9-12,14-15,20,23,25H,4-5,8,13,16H2

to

InChI=1S/C20H16F2N4O3/c21-20(22)29-15-8-6-14(7-9-15)19-25-24-17-10-23-11-18(26(17)19)28-12-16(27)13-4-2-1-3-5-13/h1-11,16,20,27H,12H2

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(OC4OCCCC4)C5=CC=CC=C5)=CN=C3

to

OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2016

Scheme:

Procedure:

AEW 85 (1.50 g, 10.4 mmol, 1.00 equiv.) was dissolved in EtOH (52 mL) and then 4-fluorobenzaldehyde (1.11 mL, 10.4 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 30 mins and then progress monitored by TLC (20% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale brown solid 2.9 g, that was dried overnight at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions.

Hazard and Risk Assessment:

Data:

TLC at 40 min (20% EtoAc in Hexane)

NMR

Strings:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

and

InChI=1S/C7H4Cl2O/c8-6-2-1-5(4-10)7(9)3-6/h1-4H

to

InChI=1S/C11H7Cl3N4/c12-8-2-1-7(9(13)3-8)4-16-18-11-6-15-5-10(14)17-11/h1-6H,(H,17,18)/b16-4+

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(Cl)C=C1Cl)=O

to

ClC1=CN=CC(N/N=C/C2=CC=C(Cl)C=C2Cl)=N1

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2016

Scheme:

Procedure:

AEW 85 (1.50 g, 10.4 mmol, 1.00 equiv.) was dissolved in EtOH (52 mL) and then 2,4-dichlorobenzaldehyde (1.82 g, 10.4 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 30 mins and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale brown solid 3.4 g, that was dried overnight at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions.

Hazard and Risk Assessment:

Data:

TLC at 40 min (10% EtoAc in Hexane)

NMR

Strings:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

and

InChI=1S/C7H4Cl2O/c8-6-2-1-5(4-10)7(9)3-6/h1-4H

to

InChI=1S/C11H7Cl3N4/c12-8-2-1-7(9(13)3-8)4-16-18-11-6-15-5-10(14)17-11/h1-6H,(H,17,18)/b16-4+

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(Cl)C=C1Cl)=O

to

ClC1=CN=CC(N/N=C/C2=CC=C(Cl)C=C2Cl)=N1

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2016

Scheme:

Procedure:

AEW 85 (1.50 g, 10.4 mmol, 1.00 equiv.) was dissolved in EtOH (52 mL) and then 3,4-dichlorobenzaldehyde (1.82 g, 10.4 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 30 mins and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Hazard and Risk Assessment:

Data:

TLC at 40 min (10% EtoAc in Hexane)

NMR

Strings:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

and

InChI=1S/C7H4Cl2O/c8-6-2-1-5(4-10)3-7(6)9/h1-4H

to

InChI=1S/C11H7Cl3N4/c12-8-2-1-7(3-9(8)13)4-16-18-11-6-15-5-10(14)17-11/h1-6H,(H,17,18)/b16-4+

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(Cl)C(Cl)=C1)=O

to

ClC1=CN=CC(N/N=C/C2=CC=C(Cl)C(Cl)=C2)=N1

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2016

Scheme:

Procedure:

AEW 85 (1.50 g, 10.4 mmol, 1.00 equiv.) was dissolved in EtOH (52 mL) and then 3,4-difluorobenzaldehyde (1.47 g, 1.14 mL, 10.4 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 30 mins and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale brown solid 3.1 g, that was dried overnight at the high vac to yield a pale brown powder in quantitative yield. Used as crude in following SSP reactions.

Hazard and Risk Assessment:

Data:

TLC at 40 min (10% EtoAc in Hexane)

little bit 'wonky' must have placed TLC at angle but gives clear result

NMR

Strings:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

and

InChI=1S/C7H4F2O/c8-6-2-1-5(4-10)3-7(6)9/h1-4H

to

InChI=1S/C11H7ClF2N4/c12-10-5-15-6-11(17-10)18-16-4-7-1-2-8(13)9(14)3-7/h1-6H,(H,17,18)/b16-4+

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(F)C(F)=C1)=O

to