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

HRID 1715345Notes

Reaction equation

HRID 1715345 reaction equation
FC(F)(F)C(C1SC(C(O)=O)=CC=1)=O.C1N=CN(C(N2C=NC=C2)=O)C=1.FC1C=CC(CS(CC(=N)NO)(=O)=O)=CC=1.[F:43][C:44]1[CH:71]=[CH:70][C:47]([CH2:48][S:49]([CH2:52]/[C:53](=[N:55]/[O:56][C:57]([C:59]2[S:60][C:61]([C:64](=[O:69])[C:65]([F:68])([F:67])[F:66])=[CH:62][CH:63]=2)=O)/[NH2:54])(=[O:51])=[O:50])=[CH:46][CH:45]=1>CN(C=O)C.O.CC#N>[F:66][C:65]([F:68])([F:67])[C:64]([C:61]1[S:60][C:59]([C:57]2[O:56][N:55]=[C:53]([CH2:52][S:49]([CH2:48][C:47]3[CH:70]=[CH:71][C:44]([F:43])=[CH:45][CH:46]=3)(=[O:51])=[O:50])[N:54]=2)=[CH:63][CH:62]=1)=[O:69]

Participants

8

Reactant 4

HCID 682631,1'-Carbonyldiimidazole2×HCID 242747015-(2,2,2-Trifluoroacetyl)thiophene-2-carboxylic acidHCID 87479772[(Z)-[1-amino-2-[(4-fluorophenyl)methylsulfonyl]ethylidene]amino] 5-(2,2,2-trifluoroacetyl)thiophene-2-carboxylateHCID 178511481HCID 178511481, compound

Product 1

HCID 445628402,2,2-Trifluoro-1-(5-(3-((4-fluorobenzylsulfonyl)methyl)-1,2,4-oxadiazol-5-yl)thiophen-2-yl)ethanone

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent4×HCID 6342AcetonitrileSolvent

Procedure

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)−.

Workup

  1. stirringthe mixture stirred at RT overnight
  2. temperaturethe mixture was heated in a microwave oven
  3. custom(sealed tube, 140° C., 2 min)
  4. customThe product was isolated by preparative RP-HPLC
  5. customThe pooled product fractions were evaporated

Sources & evidence

ORD record
ord-3b785214da5e4d468c6fa250b8b472fb
Source dataset
uspto-grants-2010_09
Patent number
US07799825B2

Reaction notes

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