1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-[1-(3,4-Dichlorobenzyl)-4-piperidinyl]-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]propanamide

HRID 1070500Notes

Reaction equation

HRID 1070500 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([NH:12][C:13](=[O:19])[CH2:14][CH2:15][C:16]([O-:18])=O)[CH2:8][CH2:7]1.[Li+].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.O[N:49]=[C:50]([C:52]1[CH:57]=[N:56][CH:55]=[CH:54][N:53]=1)[NH2:51]>ClCCl.N1C=CC=CC=1.C(N(CC)CC)C.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][N:6]1[CH2:7][CH2:8][CH:9]([NH:12][C:13](=[O:19])[CH2:14][CH2:15][C:16]2[O:18][N:51]=[C:50]([C:52]3[CH:57]=[N:56][CH:55]=[CH:54][N:53]=3)[N:49]=2)[CH2:10][CH2:11]1

Participants

9

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2737233N'-Hydroxy-2-pyrazinecarboximidamideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23689283Lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-4-oxobutanoate

Product 1

HCID 22396272N-[1-(3,4-Dichlorobenzyl)-4-piperidinyl]-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]propanamideYield 18.2%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-5-oxobutanoate (Example 351, step ii) (0.292 g) in dichloromethane (6 ml) was added N,N-dimethylformamide (1.5 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.183 g), 1-hydroxybenzotriazole hydrate (0.130 g), N′-hydroxy-2-pyrazinecarboximidamide (0.110 g) and triethylamine (0.161 g). The reaction mixture was left to stir for 24 hours before removal of dichloromethane under reduced pressure. Pyridine (5 ml) was added and heated at reflux for 5 hours. Pyridine was removed under reduced pressure followed by the addition of water. The solution was extracted three times with dichloromethane. The pooled organic phase was washed once with water, once with saturated brine and dried over magnesium sulfate. After filtration the product was azeotroped twice with toluene and was purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile). Solvent was removed under reduced pressure to give the title compound (0.067 g).

Workup

  1. waitThe reaction mixture was left
  2. temperatureheated
  3. temperatureat reflux for 5 hours
  4. customPyridine was removed under reduced pressure
  5. additionfollowed by the addition of water
  6. extractionThe solution was extracted three times with dichloromethane
  7. washThe pooled organic phase was washed once with water, once with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationAfter filtration the product
  10. customwas azeotroped twice with toluene
  11. customwas purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile)
  12. customSolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-09b988b68ac5410abc1bf58c9e4bdec5
Source dataset
uspto-grants-2005_06
Patent number
US06903085B1

Reaction notes

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