3-Piperidineacetic acid → 2-(1-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid

HRID 1948502Notes

Reaction equation

HRID 1948502 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][C:8]([OH:10])=[O:9])[CH2:2]1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[CH2:30][CH:31]([C:33]1[CH:38]=[CH:37][C:36]([C:39]2[N:43]=[C:42]([C:44]3[C:48]([CH2:49][CH2:50][CH3:51])=[C:47]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[O:46][N:45]=3)[O:41][N:40]=2)=[CH:35][CH:34]=1)[OH:32].CCN(C(N1N=NN(C2C(Cl)=CC=CC=2)C1=O)=O)C1CCCCC1>CS(C)=O.CO>[OH:32][CH:31]([C:33]1[CH:38]=[CH:37][C:36]([C:39]2[N:43]=[C:42]([C:44]3[C:48]([CH2:49][CH2:50][CH3:51])=[C:47]([C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)[O:46][N:45]=3)[O:41][N:40]=2)=[CH:35][CH:34]=1)[CH2:30][N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][C:8]([OH:10])=[O:9])[CH2:2]1

Participants

7

Reactant 4

HCID 2836963-Piperidineacetic acidHCID 2723671Tetrabutylammonium HydroxideHCID 3081363FentrazamideHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 509234242-(1-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolvent

Procedure

To a solution of 2-(piperidin-3-yl)acetic acid (51 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 room temperature 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 mixture 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 2-(1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid. MS (m+1)=517. HPLC RT=2.08 min using a 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-8babb690e1494dc7acedd52778296b83
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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