1,1'-Carbonyldiimidazole → 1-{5-[5-(2-Ethoxyphenyl)-1,3,4-oxadiazol-2-yl]-2-thienyl}-2,2,2-trifluoroethanone

HRID 1715346

Reaction equation

HRID 1715346 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]([C:5]1[S:9][C:8]([C:10]([OH:12])=O)=[CH:7][CH:6]=1)=[O:4].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:27]([O:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[C:32]([NH:34][NH2:35])=O)[CH3:28]>C(Cl)Cl.C(Cl)Cl.CN(C=O)C>[CH2:27]([O:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[C:32]1[O:12][C:10]([C:8]2[S:9][C:5]([C:3](=[O:4])[C:2]([F:1])([F:14])[F:13])=[CH:6][CH:7]=2)=[N:35][N:34]=1)[CH3:28]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 1407882-EthoxybenzhydrazideHCID 242747015-(2,2,2-Trifluoroacetyl)thiophene-2-carboxylic acid

Product 1

HCID 177473361-{5-[5-(2-Ethoxyphenyl)-1,3,4-oxadiazol-2-yl]-2-thienyl}-2,2,2-trifluoroethanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of the carboxylic acid (A1) in DCM was added to PS-CDI (1.7 eq., loading 1.30 mmol/g), and the suspension stirred at RT for 30 min. 2-Ethoxybenzohydrazide (1.3 eq.) dissolved in DCM/DMF was added, and the resulting suspension was stirred at RT overnight. The suspension was filtered and the filtrate evaporated. The crude N′-(2-ethoxybenzoyl)-5-(trifluoroacetyl)thiophene-2-carbohydrazide (MS (ES) C16H13F3N2O4S requires: 386, found: 427 (M+H20+Na)+ and 385 (M−H+e)−) was used as such, without any purification. It was dissolved in excess thionyl chloride and the solution was heated in a microwave oven (sealed tube, 100° C., 5 min) and the thionyl chloride was evaporated. The desired 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): 8.1-8.08 (1H, m), 8.06-8.01 (1H, m), 7.95-7.90 (1H, m), 7.63-7.56 (1H, m), 7.23-7.17 (1H, m), 7.16-7.09 (1H, m), 4.23 (2H, q, J=7 Hz), 1.48 (3H, t, J=7 Hz). 19F NMR (282 MHz, CD3CN); δ −74.25 (keto form), −86.14 (hydrate form). MS (ES) C16H11F3N2O3S requires: 368, found: 369 (M+H)+ and 387 (M+H2O+H)+.

Workup

  1. additionwas added
  2. stirringthe resulting suspension was stirred at RT overnight
  3. filtrationThe suspension was filtered
  4. customthe filtrate evaporated
  5. customwithout any purification
  6. dissolutionIt was dissolved in excess thionyl chloride
  7. temperaturethe solution was heated in a microwave oven
  8. custom(sealed tube, 100° C., 5 min)
  9. customthe thionyl chloride was evaporated

Sources & evidence

ORD record
ord-96ede622c92447c8a0c676eeb3697afd
Source dataset
uspto-grants-2010_09
Patent number
US07799825B2

Linked notes

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