Triazolopyrazine Series

Crude AEW 272-2 (6.12 g, 20.3 mmol, 1 equiv.) was dissolved in anhdrous CH­₂Cl₂ (203 mL) and (diacetoxyiodo)benzene (6.60 g, 20.3 mmol, 1 equiv.) was added. The reaction mixture was stirred at rt for 3 h and then quenched by the addition of a saturated aqueous solution of sodium hydrogen carbonate. Aqueous layers were separated and then extracted with CH­₂Cl₂ and then organic layers were combined and washed with brine (× 1), dried (MgSO4), filtered and evaporated. The crude mixture was then purified by

NMR

Hazard and Risk Assesment:

Strings:

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+

to

InChI=1S/C11H5Cl3N4/c12-7-2-1-6(3-8(7)13)11-17-16-10-5-15-4-9(14)18(10)11/h1-5H

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

to

ClC1=CN=CC2=NN=C(C3=CC(Cl)=C(Cl)C=C3)N21

Repeat of Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1), see also Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-2) and Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-3)

2,6-dichloropyrazine (21 g, 141 mmol, 1 eq) was dissolved in EtOH (282 mL, 0.50 M), and hydrazine hydrate (13.5 mL, 270 mmol, 2 eq) added. The reaction mixture was stirred at reflux for 8 hours.

The solvent was removed under reduced pressure to give a pale yellow solid. Water (~150 mL) and EtOAc (~200 mL) were added, and the mixture was shaken in an attempt to dissolve all solid. The organic layer was removed, the aqueous layer extracted with EtOAc (3 x 100 mL), and the combined organic layers washed with brine (~30 mL) before being concentrated under reduced pressure to yield a yellow solid 

Data:

Crude 300 MHz Data:

Hazard and Risk Assessment:

See Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1)

InChi Strings:

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

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

Apologies this lab experiment was performed on Thurs/Fri 4/5th May

Outcome:

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

Reason for Experiment: Synthesised for SSP Class 2017

Scheme:

Procedure:

AEW 85 (5.00 g, 34.6 mmol, 1.00 equiv.) was dissolved in EtOH (346 mL) and then 4-chlorobenzaldehyde (4.86 g, 34.6 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 2 h and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale yellow solid 9.8 g, that was dried at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions without NMR evaluation

Hazard and Risk Assessment:

Data:

TLC at 40 min (10% EtoAc in Hexane)

NMR

Strings:

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

to

ClC1=CN=CC2=NN=C(C3=CC=C(Cl)C=C3)N21

InChI=1S/C11H8Cl2N4/c12-9-3-1-8(2-4-9)5-15-17-11-7-14-6-10(13)16-11/h1-7H,(H,16,17)/b15-5+

to

InChI=1S/C11H6Cl2N4/c12-8-3-1-7(2-4-8)11-16-15-10-6-14-5-9(13)17(10)11/h1-6H

Apologies this lab experiment was performed on Thurs/Fri 4/5th May

Outcome:

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

Reason for Experiment: Synthesised for SSP Class 2017

Scheme:

Procedure:

AEW 85 (5.00 g, 34.6 mmol, 1.00 equiv.) was dissolved in EtOH (346 mL) and then 2,4-dichlorobenzaldehyde (6.05 g, 34.6 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 2 h and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale brown solid 11.2 g, that was dried at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions without NMR evaluation

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