Triethylamine → N-[1-(3,4-dichlorobenzyl)-4-piperidinyl]-3-[3-(2-pyridinyl)-1H-1,2,4-triazol-5-yl]propanamide

HRID 1070505Notes

Reaction equation

HRID 1070505 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([CH2:12][CH2:13][C:14]([OH:16])=O)[NH:9][N:8]=1.Cl.[Cl:18][C:19]1[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([NH2:29])[CH2:25][CH2:24]1.C(N(CC)CC)C.[OH-].[Na+]>CC(N(C)C)=O.ClCCl>[Cl:18][C:19]1[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:22][N:23]1[CH2:24][CH2:25][CH:26]([NH:29][C:14](=[O:16])[CH2:13][CH2:12][C:10]2[NH:9][N:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[N:11]=2)[CH2:27][CH2:28]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 223961833-[3-(2-pyridinyl)-1H-1,2,4-triazol-5-yl]propanoic acidHCID 223962061-(3,4-Dichloro-benzyl)-piperidin-4-ylamine hydrochloride

Product 1

HCID 22396188N-[1-(3,4-dichlorobenzyl)-4-piperidinyl]-3-[3-(2-pyridinyl)-1H-1,2,4-triazol-5-yl]propanamideYield 4.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

3-[3-(2-Pyridinyl)-1,2,4-triazol-5-yl]propanoic acid (0.218 g) in 1 ml dimethylacetamide) and N,N′-carbonyldiimidazole (0.250 g) in dichloromethane was stirred under nitrogen for 30 minutes. 1-(3,4-Dichlorobenzyl)-4-piperidinamine hydrochloride (0.316 g), and triethylamine (0.218 g) was then added and allowed to stir for 2 hours under nitrogen. 1M sodium hydroxide was added to the reaction with the resulting solution being washed three times with dichloromethane. The aqueous phase was acidified with glacial acetic acid, with the water/acetic acid being removed under reduced pressure. Water was then added and extracted three times with dichloromethane. The pooled organic phases were extracted once with water and the water removed under reduced pressure to leave a white solid. This was then triturated with diethyl ether/dichloromethane, filtered and was purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile), solvent removed to leave N-[1-(3,4-dichlorobenzyl)-4-piperidinyl]-3-[3-(2-pyridinyl)-1H-1,2,4-triazol-5-yl]propanamide (0.02 g).

Workup

  1. washbeing washed three times with dichloromethane
  2. customremoved under reduced pressure
  3. additionWater was then added
  4. extractionextracted three times with dichloromethane
  5. extractionThe pooled organic phases were extracted once with water
  6. customthe water removed under reduced pressure
  7. customto leave a white solid
  8. customThis was then triturated with diethyl ether/dichloromethane
  9. filtrationfiltered
  10. customwas purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile), solvent
  11. customremoved

Sources & evidence

ORD record
ord-22ba026248014001b3ffa8ba7e3a3e21
Source dataset
uspto-grants-2005_06
Patent number
US06903085B1

Reaction notes

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