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17th June 2014 @ 06:02

Using the PIDA cyclisation optimised by Jo, and used successfully in Resynthesis of N-(3-chlorophenyl)-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxamide (TM 14-2), TM 9-2 was obtained in 71 % yield.

scheme

 

Purified TM 7-3 Resynthesis of (E)-N-(3-chloro-2-methylphenyl)-6-(2-(4-(difluoromethoxy)benzylidene)hydrazinyl)pyrazine-2-carboxamide (TM 7-3)) (200 mg, 0.46 mmol) was stirred into DCM (10 mL), phenyliodine diacetate (PIDA) (1 eq, 0.46 mmol, 148 mg) added, and the reaction mixture stirred at RT for 6 hours.

The reaction mixture was washed with saturated NaHCO3 solution (15 mL), then the aqueous portion was re-extracted with DCM (5 x 10 mL), and concentrated under vacuum to give crude TM 9-2. The crude was purified by automatic column chromatography to give pure TM 9-2 as a pearlescent white solid (140 mg, 0.33 mmol, 71 %).

 

NMR:

1H (DMSO-d6, 400 MHz):

TM 9-2 pure 1H DMSO 400 MHz.pdf

13C (DMSO-d6, 400 MHz):

TM 9-2 pure 13C DMSO 400 MHz.pdf

HSQC (DMSO-d6, 400 MHz):

TM 9-2 pure HSQC DMSO 400 MHz.pdf

TM 9-2 pure CHARACTERISATION.zip

InChIs:

InChI=1S/C20H16ClF2N5O2/c1-12-15(21)3-2-4-16(12)27-19(29)17-10-24-11-18(26-17)28-25-9-13-5-7-14(8-6-13)30-20(22)23/h2-11,20H,1H3,(H,26,28)(H,27,29)/b25-9-

to

InChI=1S/C20H14ClF2N5O2/c1-11-14(21)3-2-4-15(11)25-19(29)16-9-24-10-17-26-27-18(28(16)17)12-5-7-13(8-6-12)30-20(22)23/h2-10,20H,1H3,(H,25,29)

HIRAC:

HIRAC.pdf
Attached Files
scheme.png
HIRAC.pdf
TM 9-2 pure HSQC DMSO 400 MHz.pdf
TM 9-2 pure 1H DMSO 400 MHz.pdf
TM 9-2 pure 13C DMSO 400 MHz.pdf
TM 9-2 pure CHARACTERISATION.zip
Comments
Re: Resynthesis of N-(3-chlorophenyl)-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxamide (TM 9-2) by Alice Williamson
17th June 2014 @ 06:27
HIRAC seen and approved. Discussed the lack of hazard information for PIDA. According to Sigma Aldrich MSDS this material is non hazardous, according to other MSDS PIDA is classed as an irritant on contact with skin, eyes, inhalation or ingestion and so will be treated as irritant.