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30th January 2014 @ 14:37

Methyl 6-chloro-2-pyrazinecarboxylate (1.03 g, 10.3 mmol) from sample 3/4 of EO 6-2 was dissolved in EtOH (14.5 mL). 2M NaOH (14.5 mL) was added, and the reaction stirred at ambient temperature for 2 h. The reaction mixture was acidified to pH3 with 2M HCl (aq). The mixture was then diluted with water (86.80 mL) and extracted with EtOAc (4 x 57.87 mL). The organic extracts were combined, washed with brine (57.87 ml) dried over Na2SO4, filtered and concentrated under vacuum to provide the title compound as a white solid (0.63 g, xx %).  NMR was derived.

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29th January 2014 @ 05:03

 

4-hydroxybenzaldehyde (1 g, 7.34 mmol) was dissolved in hydrazine hydrate (10 mL) and heated at 100 ˚C overnight then allowed to cool to rt - yellow solution. TLC showed that reaction was complete.

Data:

TLC 16 h (50/50 EtOAc/Hexane)

AEW 115-1 (50:50 EtOAc in Hex).jpg
 

Hazard and Risk Assessment:

HIRAC AEW 115-1.pdf

InChi:

InChI=1S/C7H6O2/c8-5-6-1-3-7(9)4-2-6/h1-5,9H

to

InChI=1S/C7H8N2O/c8-9-5-6-1-3-7(10)4-2-6/h1-5,10H,8H2/b9-5-


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24th January 2014 @ 16:17

Product from EO 9-1 (0.92 g) was vigorously stirred in ethanol (10 mL) and hydrazine hydrate (0.33 mL) was added. The resulting mixture was heated at 105˚C for 60 hrs.

After completion, the  solvent was removed under vacuum to yield a crude orange liquid (3.13 g). NMR data (EO 10.1 x 4 NMR)

Work up on the product was carried out involving addition of 0.1 M HCl (0.9 ml) to the product (0.9 ml) No seperation occured. EtOAc (5 ml) wqas then added. the bottom HCl layer was discarded and the top EtOAc layer washed with 5% LiCl (4 x 3 ml), disgarding the bottom LiCL layer with each wash. top layer was then collected and placed under vacuum to remove EtOAc. NMR was derived for the work up product  (EO 10.1 b x 4)

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24th January 2014 @ 00:59

Resynthesis of AEW 97 this time using MeTHF in place of CH2Clas both reaction and work-up solvent. Was suggested by Joie Garfunkle and referenced in AEW 97-7. It was hoped that problems with starting material and product solubility mihgt be overcome by the use of this solvent.

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To a well stirred solution of AEW 95-1 (100 mg,  0.38 mmol) in MeTHF (6 mL) was added PhI(OAc)2 (122 mg,  0.38 mmol) and the resulting reaction mixture was stirred at room temperature for 1 h.  

Crude 1H NMR (CDCl3):

 

Iodobenzene

AEW 97-7 crude.pdf

PIDA

PIDA.pdf
Hazard and Risk Assessment:

See 4-(5-chloro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)benzonitrile (AEW 97-1) but using MeTHF in place of CH2Cl2 which is a highly flammable solvent, class 2 M, U.

 

InChi:

InChI=1S/C12H8ClN5/c13-11-7-15-8-12(17-11)18-16-6-10-3-1-9(5-14)2-4-10/h1-4,6-8H,(H,17,18)/b16-6+

to

InChI=1S/C12H6ClN5/c13-10-6-15-7-11-16-17-12(18(10)11)9-3-1-8(5-14)2-4-9/h1-4,6-7H


23rd January 2014 @ 05:39

Starting materials:

4-(5-Chloro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)benzonitrile (AEW 97-7) and Synthesis of 2-(3,4-difluorophenyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)ethanol (AEW 113-1)

Freshly hexane washed NaH (1.5 mg, 0.06 mmol, 2 equiv.) was stirred in THF (0.3 mL) and a solution of AEW 113-1 (8 mg, 0.03 mmol, 1 equiv.) in THF (0.3 mL) was added dropwise and the resulting mixture was stirred for 15 minutes. AEW 97-7 (8 mg, 0.03 mmol, 1.01 equiv.) was added to the mixture (pale yellow solution turned deep red) and the resulting mixture was allowed to stir for a further 30 minutes.

 

Hazard and Risk Assessment:

HIRAC AEW 114-1.pdf

InChi:

InChI=1S/C13H16F2O3/c14-10-5-4-9(7-11(10)15)12(8-16)18-13-3-1-2-6-17-13/h4-5,7,12-13,16H,1-3,6,8H2

and

InChI=1S/C12H6ClN5/c13-10-6-15-7-11-16-17-12(18(10)11)9-3-1-8(5-14)2-4-9/h1-4,6-7H

to 

InChI=1S/C25H21F2N5O3/c26-19-9-8-18(11-20(19)27)21(35-24-3-1-2-10-33-24)15-34-23-14-29-13-22-30-31-25(32(22)23)17-6-4-16(12-28)5-7-17/h4-9,11,13-14,21,24H,1-3,10,15H2

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