1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 3-[3-(4-Bromo-1-methyl-1H-pyrazol-3-yl)-1,2,4-oxadiazol-5-yl]-N-[1-(3,4-dichlorobenzyl)-4-piperidinyl]propanamide

HRID 1070499Notes

Reaction equation

HRID 1070499 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.[Br:48][C:49]1[C:50]([C:55](=[N:57]O)[NH2:56])=[N:51][N:52]([CH3:54])[CH:53]=1>ClCCl.N1C=CC=CC=1.C(N(CC)CC)C.CN(C)C=O>[Br:48][C:49]1[C:50]([C:55]2[N:57]=[C:16]([CH2:15][CH2:14][C:13]([NH:12][CH:9]3[CH2:8][CH2:7][N:6]([CH2:5][C:4]4[CH:20]=[CH:21][C:22]([Cl:23])=[C:2]([Cl:1])[CH:3]=4)[CH2:11][CH2:10]3)=[O:19])[O:18][N:56]=2)=[N:51][N:52]([CH3:54])[CH:53]=1

Participants

9

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27355964-Bromo-N'-hydroxy-1-methyl-1H-pyrazole-3-carboximidamideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23689283Lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-4-oxobutanoate

Product 1

HCID 223962333-[3-(4-Bromo-1-methyl-1H-pyrazol-3-yl)-1,2,4-oxadiazol-5-yl]-N-[1-(3,4-dichlorobenzyl)-4-piperidinyl]propanamideYield 37.9%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-4-oxobutanoate (0.292 g) in dichloromethane (6 ml) was added dimethylformamide (1.5 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.183 g), 1-hydroxybenzotriazole hydrate (0.130 g), 4-bromo-N′-hydroxy-1methyl-1H-pyrazole-3-carboximidamide (0.175 g) and triethylamine (0.161 g). Reaction 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 reverse phase hplc (RPHPLC; 75%-5% 0.1% ammonium acetate/acetonitrile). Solvent was removed under reduced pressure to give the title compound (0.164 g).

Workup

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

Sources & evidence

ORD record
ord-7299cb86c56844a5b8ec67e496f46fa6
Source dataset
uspto-grants-2005_06
Patent number
US06903085B1

Reaction notes

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