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12th September 2016 @ 12:55

Haochuan's attempts at forming crystals of HM 3-2 were successful. The structure was detemined by Peter Turner of the X-ray Crystal Structure Facility in the School of Chemistry, University of Sydney, and forwarded to the group by email on Sept 1st 2016. Files appended.

HM 3-2

 

3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine

BrC1=NN=C2C=NC=C(Cl)N21

InChI=1S/C5H2BrClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H

UGKMQVWBWSZEBB-UHFFFAOYSA-N

Synthesis of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (HM 3-2)

Crystallizing HM 3-2

Attached Files
14th September 2015 @ 03:18

 

AEW 85-8 (3.80 g, 26.3 mmol) was dissolved in EtOH (200 mL) and 4-(trifluoromethoxy)benzaldehyde (5.00 g, 26.3 mmol, 1 equiv.) was added. The reaction mixture (clear orange solution) was stirred at room temperature for 30 mins (precipitate formed) and left to stir for a further 6 h.

Solvents removed in vacuo to yield a yellow solid (quant).

Crude 200 MHz NMR recorded and then used in AEW 250-1 withouut futher purification (1 spot by TLC), too many proton peaks.

Data:

AEW 250-1 proton.pdf
AEW 250-1 crude.zip

AEW 250-1 (50:50 EtOAc:Hex).jpeg

Hazard and Risk Assessment:

HIRAC AEW 250-1.pdf
HIRAC AEW 250-1.doc

Strings

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

and

InChI=1S/C8H5F3O2/c9-8(10,11)13-7-3-1-6(5-12)2-4-7/h1-5H

to

InChI=1S/C12H8ClF3N4O/c13-10-6-17-7-11(19-10)20-18-5-8-1-3-9(4-2-8)21-12(14,15)16/h1-7H,(H,19,20)/b18-5+

 

ClC1=CN=CC(NN)=N1

and

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

to

ClC1=CN=CC(N/N=C/C2=CC=C(OC(F)(F)F)C=C2)=N1

Attached Files
9th July 2015 @ 02:04

Not using Ethanol as solvent, using only aqueous ammonia. (First attempt, TZ 1-1)

GitHub Issue #316


4rocedure:

2,6-dichloropyrazine (500 mg, 3.36 mmol, 1 eq) and ammona solution (6.7 mL, 0.50 M, 28% aqueous) were combined in a sealed tube. The reaction mixture was stirred at 100 degrees celcius for 18 hours. 

The reaction mixture was diluted with EtOAc (30 mL) and a saturated aqueous solution of sodium hydrogen carbonate (20 mL). The biphasic mixture was shaken in a separating funnel and then organic layers separated. Aqueous layers were washed with EtOAc (30 mL) and then combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered and evaporated to give a pale yellow crystalline solid, which was dried in vacuo (290.1 mg, 67 % yield). No further purification, to be scaled-up on Monday.

Data:


TLC (EtOAc/petroleum benzine 50:50)

 crude NMR 300MHz, desired product with trace SM

TZ 1-2 crude 300 MHz.pdf
TZ 1-2 crude.zip

1H NMR (CDCl3 300 MHz): δ 7.91 (1H, s),  7.86 (1H, s), 4.71 (2H, bs).

See SM spectra (Synthesis of 6-chloropyrazin-2-amine (TZ 1-1))

Hazard and Risk Assessment:

 

HIRAC TZ 1-2.pdf

Literature:

http://worldwide.espacenet.com/publicationDetails/originalDocument?CC=WO&NR=2013068755A1&KC=A1&FT=D&ND=&date=20130516&DB=&&locale=en_EP

Strings:

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(N)=N1

 

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

to

InChI=1S/C4H4ClN3/c5-3-1-7-2-4(6)8-3/h1-2H,(H2,6,8)

Attached Files
7th July 2015 @ 05:05

No reaction.

Started Wednesday 8th of July. Started 11 am and reached temp 11:30 am. 

 


Procedure:

Following procedure for AEW 85-7 

2,6-dichloropyrazine (500 mg, 3.36 mmol, 1 eq) was dissolved in EtOH (6.7 mL, 0.50 M) and ammona solution (0.2 mL, 3.36 mmol, 1 eq, 28% aqueous) was added. The reaction mixture was stirred at reflux for 1 hour.

TLC (1 hour) showed only starting material looked under UV light and revealed with Goofy dip and saw only SM.

TLC (overnight) showed only starting material looked under UV light.

Purification of the residue.

step 1 seperate the ethanol remaining by using rotary evaporation 
step 2 work-up using ethyl acetate and water
step 3 rotary evaporation of the solution obtianed in step2 and we got the crude material (61 mg) Lots of material lost up rotary evaporator and on vac line - caution in future.

NMR of crude material showed only SM, but problem with shim so will reconfirm on 300 MHz tomorrow - confirmed SM.

Data:

TLC (EtOAc/petroleum benzine 50:50) 1hour

TZ1-1 TLC(no flash 1 hour).JPG
TZ1-1 TLC(with flash 1 hour).JPG
TZ1-1 TLC (revealed by Goofy).JPG

TLC (EtOAc/petroleum benzine 50:50) overnight

TZ1-1 TLC(no flash overnight).JPG
TZ1-1 TLC(with flash overnight).JPG

300 MHz crude NMR - SM

TZ 1-1 crude 2 300 MHz.pdf
TZ 1-1 crude 2.zip

Hazard and Risk Assessment:

 

HIRAC TZ 1-1.pdf

Strings:

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(N)=N1

 

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

to

InChI=1S/C4H4ClN3/c5-3-1-7-2-4(6)8-3/h1-2H,(H2,6,8)

Linked Entries
Attached Files
25th June 2015 @ 04:44

Note replaced solvent (MeCN/AcOH with EtOH to improve procedure)

GitHub Issue 

 

AEW 85 (4.2 g, 29.1 mmol) was stirred into a solution of ethanol (90 mL).

4-(difluoromethoxy)benzaldehyde (5.0 g, 29.1 mmol) was added and the reaction mixture (yellow ppt) was stirred at room temperature for 30 minutes when it solidified (reaction complete), EtOH (20 mL) was added and the rection mixture stirred overnight to yield a yellow ppt. Solvents removed in vacuo to provide a yellow solid (8.72 g, >100%) crude.

NMR shows 5:1 product to aldehyde SM but used directly in next step, will separate aldehyde after cyclisation.

Data:

 

AEW 240 and 244-1.JPG

NMR 200 MHz

AEW 204 crude.pdf
AEW 204 crude.zip

NMR shows 5:1 product to aldehyde SM

Hazard and Risk Assessment: 

HIRAC AEW 217-1.pdf

InChI strings

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

and

InChI=1S/C8H6F2O2/c9-8(10)12-7-3-1-6(5-11)2-4-7/h1-5,8H

to

InChI=1S/C12H9ClF2N4O/c13-10-6-16-7-11(18-10)19-17-5-8-1-3-9(4-2-8)20-12(14)15/h1-7,12H,(H,18,19)/b17-5+


SMILES

ClC1=CN=CC(NN)=N1

and

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

to

ClC1=CN=CC(N/N=C/C2=CC=C(OC(F)F)C=C2)=N1


 
Attached Files