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 1070499노트

반응식

HRID 1070499 반응식
[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

참가 물질

9

반응물 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

생성물 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]propanamide수율 37.9%

시약·촉매·용매 4

HCID 1049Pyridine용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7299cb86c56844a5b8ec67e496f46fa6
출처 데이터셋
uspto-grants-2005_06
특허 번호
US06903085B1

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