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26th November 2014 @ 05:25

Synthesis performed by Evan Hockings, James Manton-Hall, Andreas Orsmond and Hugh Russell.

Repeat of Synthesis of (E)-2-chloro-6-(2-(pyridin-3-ylmethylene)hydrazinyl)pyrazine (AEW 199-2).

SGS 1-1 (crude, 1.01 g, 7.0 mmol) was stirred into MeCN (12 mL). 4-Pyridinecarboxaldehyde (0.75 g, 7.0 mmol, density 1.137 g/mL) was added and the reaction mixture (terracotta) was stirred at room temperature for 24 h.  Solvent was removed in vaccuo to produce a pale orange solid.

 

InChi:

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

and

InChI=1S/C6H5NO/c8-5-6-2-1-3-7-4-6/h1-5H

to

InChI=1S/C10H8ClN5/c11-9-6-13-7-10(15-9)16-14-5-8-2-1-3-12-4-8/h1-7H,(H,15,16)/b14-5+


Smiles

ClC1=CN=CC(NN)=N1

and

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

to

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

Attached Files
25th November 2014 @ 04:37

5-chloro-[1,2,4]triazolom4,3-a]pyrazine (500 mg, 3.24 mmol) was combined with N-bromosuccinimide (0.98 g, 3.56 mmol, 1.7 eq) in chloroform (25 mL) and refluxed from 4 pm. TLC showed new spots (plus two for SM) but still SM so left to stir o/n.

TLC:

AEW 206-2 (50:50 EtOAc:Hex) 24 h.JPG

N-bromosuccinamide purified prior to AEW 206-1 by recrystalliation in water:

20 g in 200 mL, heated to 95 ˚C until all solid dissolved and then left to cool at rt until white crystals formed. Then cooled to 0 ˚C for 30 minutes, filtered washed with cold water to yield a white solid (15 g).

Hazard and Risk Assessment:

See Synthesis of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (TM 57-1)

 

Strings:

InChI=1S/C5H3ClN4/c6-4-1-7-2-5-9-8-3-10(4)5/h1-3H

to

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

ClC1=CN=CC2=NN=CN21

to 

ClC1=CN=CC2=NN=C(Br)N21

Attached Files
24th November 2014 @ 06:44

AEW 207-1  (from Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-4)): 381 mg, 3.46 mmol) was dissolved in toluene (5 mL), triethyl orthoformate (0.737 ml, 6.92 mmol, 2 eq) and TsOH (60 mg, 0.35 mmol, 10 mol%) added, and the reaction mixture refluxed (bath temp 110 oC) for 24 h. 


Hazard and Risk Assessment:

See Synthesis of 5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (TM 37-1)

 

Strings:

InChI=1S/C4H6N4/c5-8-4-3-6-1-2-7-4/h1-3H,5H2,(H,7,8)

to

InChI=1S/C5H4N4/c1-2-9-4-7-8-5(9)3-6-1/h1-4H

 

NNC1=NC=CN=C1

to

C12=NN=CN1C=CN=C2


Attached Files
24th November 2014 @ 06:24


2-Chloro-6-hydrazinylpyrazine (from Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-4)): 8.00 g, 55.3 mmol) was dissolved in toluene (150 mL), triethyl orthoformate (18.3 ml, 110 mmol, 2 eq) and TsOH (500 mg, 2.76 mmol, 10 mol %) added, and the reaction mixture refluxed (bath temp 110 oC) for 24 h. 


Hazard and Risk Assessment:

See Synthesis of 5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (TM 37-1)


Strings:

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

to

InChI=1S/C5H3ClN4/c6-4-1-7-2-5-9-8-3-10(4)5/h1-3H


NNC1=NC(Cl)=CN=C1

to

ClC1=CN=CC2=NN=CN21

Attached Files
20th November 2014 @ 15:03

Reaction Scheme: 


Experimental Procedure: 

 see Synthesis of (E)-4-((2-(6-chloropyridin-2-yl)hydrazono)methyl)benzonitrile (JS 10-1) 

To a solution of JS 10-1 (100 mg, 0.39 mmol, crude) stirred in CH2Cl(5.5 mL) was added Iodosobenzene diacetate (138.5 mg, 0.43 mmol). The reaction was stirred at room temperature and was monitored by TLC. 

After one hour the reaction was complete as indicated by TLC (100% EtOAc). The reaction was washed with NaHCO3 (10 mL) and the layers separated. The water layer was extracted with DCM ( 3 x 10 mL) and the combined organic layers were then dried over MgSO4 before the solution was filtered and the solvents removed in vacuo. 

The crude product was purified using flash column chromatography (from 100% EtOAc to 9/1 EtOAc /MeOH in a gradient) to yield compound 5 ( 90 mg, 91% yield % ) 

Risk Assessment :

 

JS 8-1.docx

SMILES 

ClC1=CC=CC(N/N=C/C2=CC=C(C#N)C=C2)=N1

to

ClC1=CC=CC2=NN=C(C3=CC=C(C#N)C=C3)N21

 

InchI Strings

InChI=1S/C13H9ClN4/c14-12-2-1-3-13(17-12)18-16-9-11-6-4-10(8-15)5-7-11/h1-7,9H,(H,17,18)/b16-9+

to

InChI=1S/C13H7ClN4/c14-11-2-1-3-12-16-17-13(18(11)12)10-6-4-9(8-15)5-7-10/h1-7H

NMR

JS 11-1 .png
Linked Posts
Attached Files