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17th June 2014 @ 05:06

See: Synthesis of N-(3-chloro-2-fluorophenyl)-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxamide (TM 19-1).

Using the method optimised by Jo and applied 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 19-2 was obtained in 63 % yield.

scheme

Purified TM 17-2 (Resynthesis of (Z)-N-(3-chloro-2-fluorophenyl)-6-(2-(4-(difluoromethoxy)benzylidene)hydrazinyl)pyrazine-2-carboxamide (TM 17-2)) (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 19-2. The crude was purified by automatic column chromatography to give pure TM 19-2 as a pearlescent white solid (125 mg, 0.29 mmol, 63 %).

 

NMR:

1H (DMSO-d6, 400 MHz):

TM 19-2 pure 1H DMSO 400 MHz.pdf

13C (DMSO-d6, 400 MHz):

TM 19-2 pure 13C DMSO 400 MHz.pdf

Raw:

TM 19-2 pure CHARACTERISATION.zip

 

InChIs:

InChI=1S/C19H13ClF3N5O2/c20-13-2-1-3-14(17(13)21)27-18(29)15-9-24-10-16(26-15)28-25-8-11-4-6-12(7-5-11)30-19(22)23/h1-10,19H,(H,26,28)(H,27,29)/b25-8-

to

InChI=1S/C19H11ClF3N5O2/c20-12-2-1-3-13(16(12)21)25-18(29)14-8-24-9-15-26-27-17(28(14)15)10-4-6-11(7-5-10)30-19(22)23/h1-9,19H,(H,25,29

 

HIRAC:

HIRAC.pdf
Attached Files
HIRAC.pdf
scheme.png
TM 19-2 pure 13C DMSO 400 MHz.pdf
TM 19-2 pure 1H DMSO 400 MHz.pdf
TM 19-2 pure CHARACTERISATION.zip
Comments
Re: Resynthesis of N-(3-chloro-2-fluorophenyl)-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxamide (TM 19-2) by Alice Williamson
17th June 2014 @ 06:28
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.