Nipecotic Acid → 1-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

HRID 1948470Notes

Reaction equation

HRID 1948470 reaction equation
Br[CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[C:20]([CH2:21][CH2:22][CH3:23])=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:18][N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)[OH:4].[NH:30]1[CH2:35][CH2:34][CH2:33][CH:32]([C:36]([OH:38])=[O:37])[CH2:31]1.C1CCN2C(=NCCC2)CC1>CS(C)=O>[OH:4][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[C:20]([CH2:21][CH2:22][CH3:23])=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:18][N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)[CH2:2][N:30]1[CH2:35][CH2:34][CH2:33][CH:32]([C:36]([OH:38])=[O:37])[CH2:31]1

Participants

5

Reactant 3

HCID 4498Nipecotic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 509232741-(2-Hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 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) and piperidine-3-carboxylic acid (25.6 mg, 0.198 mmol) in DMSO (2 mL) was added DBU (0.030 mL, 0.198 mmol). The reaction mixture was heated at 80° C. for 2 hours. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 18 mg 1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.16 (2H, dd, J=8.35, 1.98 Hz), 7.83 (2H, dd, J=7.91, 1.54 Hz), 7.56-7.75 (5H, m), 5.13-5.39 (1H, m), 4.11-4.31 (2H, m), 3.21-3.41 (3H, m), 2.96-3.05 (2H, m), 2.70-2.85 (1H, m), 1.75-2.14 (4H, m), 1.62-1.77 (2H, m), 1.36-1.56 (1H, m), 0.98 (3H, t, J=7.36 Hz). MS (m+1)=503. HPLC Peak RT=3.35 minutes (Analytical Method A). Purity=90%.

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by HPLC
  3. custom25 minute
  4. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-57d3b7960af04a279651f7812988ea62
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…