1,1'-Carbonyldiimidazole → (RS)-N-(4-cyano-benzyl)-2-ethoxy-2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-acetamide

HRID 1828116Notes

Reaction equation

HRID 1828116 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([C:15]1[CH:31]=[CH:30][C:18]([CH2:19][NH:20][C:21](=[O:29])[CH:22]([O:26][CH2:27][CH3:28])[C:23]([OH:25])=O)=[CH:17][CH:16]=1)#[N:14].[C:32](=[N:40]O)([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1>[C:13]([C:15]1[CH:16]=[CH:17][C:18]([CH2:19][NH:20][C:21](=[O:29])[CH:22]([O:26][CH2:27][CH3:28])[C:23]2[O:25][N:40]=[C:32]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:39]=2)=[CH:30][CH:31]=1)#[N:14]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 69186N'-HydroxybenzenecarboximidamideHCID 22064699(RS)-N-(4-cyano-benzyl)-2-ethoxy-malonamic acid

Product 1

HCID 22064678(RS)-N-(4-cyano-benzyl)-2-ethoxy-2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
140 °C

Procedure

To a solution under N2 of 1,1′-carbonyldiimidazole (272 mg) in THF (10 ml) was added a solution of (RS)-N-(4-cyano-benzyl)-2-ethoxy-malonamic acid (400 mg) in THF (10 ml). The mixture was stirred for 30 min before addition of a solution of benzamidoxime (228 mg) in THF (20 ml). After stirring 18 h the solvent was evaporated. The crude product was dissolved in EtOAc and extracted with HCl 0.1 N, NaHCO3 and brine. After drying (MgSO4) the solvent was evaporated. The resulting white powder was redissolved in DMF (15 ml) and this solution was heated 5 min in a sealed tube at 140° C. using microwave radiation. DMF was removed, the residue was diluted with EtOAc and washed twice with water. The aqueous phases were extracted with more EtOAc. The combined organic phases were dried over MgSO4 and the solvent was evaporated. Flash chromatography (MeCl2/Et2O, from 100:0 to 95:5) yielded (RS)-N-(4-cyano-benzyl)-2-ethoxy-2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-acetamide, 305 mg (55%); lightly yellow oil. MS 363.1 (100, [M+H]+), 380 (53, [M+NH4]+).

Workup

  1. customwas evaporated
  2. dissolutionThe crude product was dissolved in EtOAc
  3. extractionextracted with HCl 0.1 N, NaHCO3 and brine
  4. dry with materialAfter drying (MgSO4) the solvent
  5. customwas evaporated
  6. dissolutionThe resulting white powder was redissolved in DMF (15 ml)
  7. customDMF was removed
  8. additionthe residue was diluted with EtOAc
  9. washwashed twice with water
  10. extractionThe aqueous phases were extracted with more EtOAc
  11. dry with materialThe combined organic phases were dried over MgSO4
  12. customthe solvent was evaporated

Sources & evidence

ORD record
ord-8962af9794dd4ab98b0d418056b80eb0
Source dataset
uspto-grants-2006_06
Patent number
US07056932B2

Reaction notes

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