Tetrabutylammonium Hydroxide → 4-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperazine-2-carboxylic acid

HRID 1948501Notes

Reaction equation

HRID 1948501 reaction equation
[C:1]([CH:4]1[CH2:9][NH:8][CH2:7][CH2:6][NH:5]1)([OH:3])=[O:2].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[CH2:29][CH:30]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[N:42]=[C:41]([C:43]3[C:47]([CH2:48][CH2:49][CH3:50])=[C:46]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[O:45][N:44]=3)[O:40][N:39]=2)=[CH:34][CH:33]=1)[OH:31].CCN(C(N1N=NN(C2C(Cl)=CC=CC=2)C1=O)=O)C1CCCCC1>CS(C)=O.CO>[OH:31][CH:30]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[N:42]=[C:41]([C:43]3[C:47]([CH2:48][CH2:49][CH3:50])=[C:46]([C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)[O:45][N:44]=3)[O:40][N:39]=2)=[CH:34][CH:33]=1)[CH2:29][N:8]1[CH2:7][CH2:6][NH:5][CH:4]([C:1]([OH:3])=[O:2])[CH2:9]1

Participants

7

Reactant 4

HCID 2723671Tetrabutylammonium HydroxideHCID 2723758Piperazine-2-carboxylic acidHCID 3081363FentrazamideHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 509234234-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperazine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolvent

Procedure

To a solution of 2-carboxypiperazine (47 mg, 0.36 mmol) in 0.5 mL dry DMSO was added tetrabutylammonium hydroxide (0.360 mL, 360 μmol, 1M in THF) and the reaction mixture was stirred at rt for 15 min. 2-bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol, Preparation 1C (30 mg, 0.066 mmol) was dissolved in 0.5 mL DMSO and added and the reaction was agitated at 400 rpm on an INNOVA® platform shaker at 80° C. for 1.5 hours. The reaction was diluted with 250 μL of MeOH and purified by HPLC (MeOH—H2O-TFA) to give 4-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperazine-2-carboxylic acid. MS (m+1)=504. HPLC RT=2.06 min Waters Masslynx instrument equipped with a 19×100 mm 5 uM C18 column and a method of 0-100% B solvent over 15 min at a flow rate of 20 mL/min. Solvent A is 5:95 acetonitrile/water; solvent B is 95:5 acetonitrile/water and both contain 0.5% TFA.

Workup

  1. additionadded
  2. custompurified by HPLC (MeOH—H2O-TFA)

Sources & evidence

ORD record
ord-9929bb60b8da43ec9458c1df94f77ad8
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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