Sodium Iodide → (S)-1-(4-(5-(5-Phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenethyl)piperidine-3-carboxylic acid

HRID 1948555Notes

Reaction equation

HRID 1948555 reaction equation
[C:1](=[O:4])([O-])[O-:2].[Cs+].[Cs+].Br[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:20]=[C:19]([C:21]3[C:25]([CH2:26][CH2:27][CH3:28])=[C:24]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[O:23][N:22]=3)[O:18][N:17]=2)=[CH:12][CH:11]=1.[I-].[Na+].[CH3:37][N:38]1[C:42](=O)[CH2:41][CH2:40][CH2:39]1>>[C:29]1([C:24]2[O:23][N:22]=[C:21]([C:19]3[O:18][N:17]=[C:16]([C:13]4[CH:14]=[CH:15][C:10]([CH2:9][CH2:8][N:38]5[CH2:37][CH2:42][CH2:41][C@H:40]([C:1]([OH:2])=[O:4])[CH2:39]5)=[CH:11][CH:12]=4)[N:20]=3)[C:25]=2[CH2:26][CH2:27][CH3:28])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 583741553-(4-(2-Bromoethyl)phenyl)-5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazole

Product 1

HCID 58374066(S)-1-(4-(5-(5-Phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenethyl)piperidine-3-carboxylic acid

Conditions

Temperature
80 °C

Procedure

To a mixture of (S)-piperidine-3-carboxylic acid, HCl (29.5 mg, 0.178 mmol) in NMP (2 mL) was added cesium carbonate (97 mg, 0.297 mmol). The reaction mixture was stirred for 30 minutes. Next, 3-(4-(2-bromoethyl)phenyl)-5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazole (26 mg, 0.059 mmol) and sodium iodide (2 mg, 0.013 mmol) were added. The reaction mixture was heated at 80° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 20 mL/min. The resulting material was 4mg of (S)-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenethyl)piperidine-3-carboxylic acid as a TFA salt. MS (m+1)=487. HPLC Peak RT=3.67 minutes (Analytical Method A). 1H NMR (400 MHz, MeOH-d3) δ ppm 8.03 (2H, m), 7.71 (2H, dd, J=7.91, 1.54 Hz), 7.46-7.56 (3H, m), 7.39 (2H, m, J=8.57 Hz), 4.26-4.49 (2H, m), 3.27 (1H, dd, J=12.96, 3.95 Hz), 3.05-3.15 (3H, m), 2.86-3.04 (5H, m), 2.65-2.81 (1H, m), 1.89-2.03 (1H, m), 1.57-1.77 (5H, m), 0.95 (3H, t, J=7.36 Hz).

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by HPLC
  3. custom25 minute

Sources & evidence

ORD record
ord-4905ce921a28433d897293edcc66c210
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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