1,1'-Carbonyldiimidazole → [3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-(4-ethylphenyl)piperidin-1-yl](3-hydroxyazetidin-1-yl)methanone

HRID 661288Notes

Reaction equation

HRID 661288 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][N:13]([C:15]([N:17]3[CH2:20][CH:19]([OH:21])[CH2:18]3)=[O:16])[CH2:12][CH:11]([C:22](O)=[O:23])[CH2:10]2)=[CH:5][CH:4]=1)[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.O[N:38]=[C:39]([O:41][CH2:42][CH3:43])[NH2:40]>CN(C=O)C.O1CCOCC1>[CH2:42]([O:41][C:39]1[N:40]=[C:22]([CH:11]2[CH2:10][CH:9]([C:6]3[CH:5]=[CH:4][C:3]([CH2:1][CH3:2])=[CH:8][CH:7]=3)[CH2:14][N:13]([C:15]([N:17]3[CH2:20][CH:19]([OH:21])[CH2:18]3)=[O:16])[CH2:12]2)[O:23][N:38]=1)[CH3:43]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 580023695-(4-Ethylphenyl)-1-[(3-hydroxyazetidin-1-yl)carbonyl]piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

Product 1

HCID 58116469[3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-(4-ethylphenyl)piperidin-1-yl](3-hydroxyazetidin-1-yl)methanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 80.0 mg (0.241 mmol) of the carboxylic acid from Example 14A in 0.97 ml of DMF and 1.93 ml of 1,4-dioxane were added, at 60° C., 99.8 mg (0.615 mmol) of 1,1′-carbonyldiimidazole, and the mixture was stirred for 3 h. Subsequently, the mixture was admixed with 50.1 mg (0.481 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and then stirred at RT for 2 h and then at 120° C. for 2.5 h. The reaction solution was concentrated under reduced pressure and purified directly by means of preparative HPLC. Yield: 33.1 mg (33% of theory)

Workup

  1. waitat 120° C. for 2.5 h
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. custompurified directly by means of preparative HPLC

Sources & evidence

ORD record
ord-83d071207a4d4db8a0b1634e005a7d80
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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