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30th June 2015 @ 06:31

Started at 15:30.

2,6-dichloropyrazine (21 g, 141 mmol) was dissolved in ethanol (282 mL), and hydrazine hydrate (13.5 mL, 270 mmol) was added. The reaction mixture was refluxed (80oC, 7 h).

HIRAC:

hazard-and-assessment-form.pdf

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)

Attached Files
29th June 2015 @ 10:37

Reaction Scheme

Procedure

AEW 204 (~29.1 mmol) was stirred into CH2Cl2 (250 mL). PhI(OAc)(9.37 g, 29.1 mmol) was added and the resulting solution was stirred at room temperature overnight. The orange/brown suspension turned to a read/orange solution. The reaction was quenched by addition of a saturate aqueous solution of sodium hydrogen carbonate (150 mL) and diluted with dichloromethane (50 mL). Organic layers were separated and aqueous layers washed with dichloromethane (100 ml). Combined organic layers were washed with a saturate aqueous solution of sodium hydrogen carbonate (100 mL), brine (100 mL), dried (MgSO4), filtered and evaporated to give a brown/orange sludge. Ethyl Acetate (~90 mL) was added and the mixture heated to ~70 ˚C with intermittent sonication, until all of the solid had dissolved. The solution was left to cool to room temperature and a solid precipated from the solution. The mixture was cooled in ice water bath for a further 30 minutes and then filtered and washed with cod ethyl acetate (20 mL) to yield a gold solid that was dried at the high vac (4.49 g, 15.1 mmol, 52% yield). (NMR showed pure product). The residue was reduced to ~50 mL and left in the fridge overnight. A red/orange solid had formed at the bottom of the flask and was broken up by sonication. The solid was filtered and washed with cold ethyl acetate (~15 mL) to give a red/orange crystalline material that was dried at the high vac (1.71 g, 5.76 mmol, 20% yield). 

TLC shows product in mother liquor, to be columned. Current total: (6.2 g, 72% yield)

 

Data:

AEW 205 second cryst 300 MHz.pdf
AEW 205 2nd recryst.zip
205 crude first batch.zip

HIRAC

 See 5-chloro-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine (JU 19-1)

InChI strings

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+

to

InChI=1S/C12H7ClF2N4O/c13-9-5-16-6-10-17-18-11(19(9)10)7-1-3-8(4-2-7)20-12(14)15/h1-6,12H

SMILES

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

to

ClC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

Linked Entries
Attached Files
29th June 2015 @ 08:00

Crude AEW 244-1 (~2.35 mmol) was dissolved in CH2Cl2 (23 mL) (orange/brown solution) and PIDA (757 mg, 2.35 mmol, 1 equiv.) was added and the reaction mixture stirred at room temperature for


Data:



Strings:

ClC1=CN=CC(N/N=C/C2CCCN(C2)C(OC(C)(C)C)=O)=N1

to

ClC1=CN=CC2=NN=C(C3CN(CCC3)C(OC(C)(C)C)=O)N21

InChI=1S/C15H22ClN5O2/c1-15(2,3)23-14(22)21-6-4-5-11(10-21)7-18-20-13-9-17-8-12(16)19-13/h7-9,11H,4-6,10H2,1-3H3,(H,19,20)/b18-7+

to

InChI=1S/C15H20ClN5O2/c1-15(2,3)23-14(22)20-6-4-5-10(9-20)13-19-18-12-8-17-7-11(16)21(12)13/h7-8,10H,4-6,9H2,1-3H3

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
25th June 2015 @ 04:26

AEW 85 (340 mg, 2.35 mmol) was stirred into a solution of ethanol (6 mL).

1-Boc-piperidine-3-carboxaldehyde (500 mg, 2.35 mmol) was added and the reaction mixture stirred at room temperature for 4 hours. A yellow/orange ppt formed after 20 minutes but reaction was left to stir for the complete 4 hours. Solvent evaporated to yield a yellow orange solid (779 mg, 98%) crude yield.

NMR showed product. Used directly in AEW 245-1

 

Data:

NMR 200 MHz

AEW 244-1 crude.pdf
AEW 244-1 crude.zip

Hazard and Risk Assessment: 

HIRAC AEW 217-1.pdf

 

Strings:

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

and

InChI=1S/C11H19NO3/c1-11(2,3)15-10(14)12-6-4-5-9(7-12)8-13/h8-9H,4-7H2,1-3H3

to

InChI=1S/C15H22ClN5O2/c1-15(2,3)23-14(22)21-6-4-5-11(10-21)7-18-20-13-9-17-8-12(16)19-13/h7-9,11H,4-6,10H2,1-3H3,(H,19,20)/b18-7+

ClC1=CN=CC(NN)=N1

and

O=C([H])C1CCCN(C1)C(OC(C)(C)C)=O

to

ClC1=CN=CC(N/N=C/C2CCCN(C2)C(OC(C)(C)C)=O)=N1

Attached Files