Piperidine → 1-Isopropyl-4-{5-[5-(4-piperidin-1-ylmethylphenyl)[1,2,4]oxadiazol-3-yl]pyridin-2-yl}piperazine

HRID 80901Notes

Reaction equation

HRID 80901 reaction equation
Cl.Cl[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:26][CH2:25][N:24]([CH:27]([CH3:29])[CH3:28])[CH2:23][CH2:22]4)=[N:19][CH:20]=3)[N:11]=2)=[CH:6][CH:5]=1.[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>C(O)C>[CH:27]([N:24]1[CH2:23][CH2:22][N:21]([C:18]2[CH:17]=[CH:16][C:15]([C:12]3[N:11]=[C:10]([C:7]4[CH:6]=[CH:5][C:4]([CH2:3][N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)=[CH:9][CH:8]=4)[O:14][N:13]=3)=[CH:20][N:19]=2)[CH2:26][CH2:25]1)([CH3:29])[CH3:28]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 131730773HCID 131730773, compound

Product 1

HCID 580065391-Isopropyl-4-{5-[5-(4-piperidin-1-ylmethylphenyl)[1,2,4]oxadiazol-3-yl]pyridin-2-yl}piperazineYield 100%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(5-(5-(4-chloromethylphenyl)[1,2,4]oxadiazol-3-yl)pyridine-2-yl)-4-isopropylpiperazine, hydrochloride (280 mg, 0.65 mmol, prepared as described in Example 41, 96% ethanol (20 mL) and piperidine (0.2 mL, 2.1 mmol) heated at reflux temperature for 4 h. The mixture was evaporated to give a solid residue which was purified by column chromatography on silica gel (75 g, Kiselgel 60, mesh 0.040-0.63) eluting with a mixture of dichloromethane and methanol (7:3). Collecting the proper fractions afforded 310 mg (100%) of 1-isopropyl-4-{5-[5-(4-piperidin-1-ylmethylphenyl)[1,2,4]oxadiazol-3-yl]pyridin-2-yl}piperazine. The free base (310 mg) was dissolved into ethanol (20 mL) and a 1 N hydrochloric acid solution (1.5 mL) was added. When dissolved, the mixture was evaporated and the solid residue was re-crystallised from ethanol to give 240 mg (67%) of the title compound.

Workup

  1. customprepared
  2. temperatureheated
  3. temperatureat reflux temperature for 4 h
  4. customThe mixture was evaporated
  5. customto give a solid residue which
  6. customwas purified by column chromatography on silica gel (75 g, Kiselgel 60, mesh 0.040-0.63)
  7. washeluting with a mixture of dichloromethane and methanol (7:3)
  8. customCollecting the proper fractions

Sources & evidence

ORD record
ord-7b8e37fdbb07463c91346243045a0be8
Source dataset
uspto-grants-2014_09
Patent number
US08846677B2

Reaction notes

Loading…