1,1'-Carbonyldiimidazole → 2,2,2-Trifluoro-1-(5-(3-((4-fluorobenzylsulfonyl)methyl)-1,2,4-oxadiazol-5-yl)thiophen-2-yl)ethanone

Participants

Reaction Steps

The above acid (A1) was dissolved in DMF and a solution of CDI (1.1 eq) in DMF was added. The mixture was stirred at RT for 30 min, then 2-[(4-fluorobenzyl)sulfonyl]-N-hydroxyethanimidamide (1.1 eq.) in DMF was added and the mixture stirred at RT overnight. The resulting intermediate (1Z)-2-[(4-fluorobenzyl)sulfonyl]-N′-({[5-(trifluoroacetyl)-2-thienyl]carbonyl}oxy)ethanimidamide (MS (ES) C16H12F4N2O5S2 requires: 452, found: 471 (M+H2O+H)+) was not isolated, instead CDI (1.1 eq) in DMF was added and the mixture was heated in a microwave oven (sealed tube, 140° C., 2 min). The product was isolated by preparative RP-HPLC, using H2O (0.1% TFA) and MeCN (0.1% TFA) as eluents (column: C18). The pooled product fractions were evaporated to afford the title compound. 1H NMR (300 MHz, CD3CN): 8.1-8.07 (2H, m), 7.91 (0.1H, d, J=4 Hz, hydrate form), 7.58-7.49 (2H, m), 7.41 (0.1H, d, J=4 Hz, hydrate form), 7.25-7.12 (2H, m), 4.57 (2H, s), 4.54 (2H, s), 4.48 (0.2H, s, hydrate form). 19F NMR decoupled (282 MHz, CD3CN): −73.78 (keto form), −85.45 (hydrate form), −114.51. MS (ES) C16H10F4N2O4S2 requires: 434, found: 453 (M+H2O+H)+, MS (ES−) 433 (M−H+e)−.

Provenance & Evidence