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 1070500노트

반응식

HRID 1070500 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.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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 1049Pyridine용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-09b988b68ac5410abc1bf58c9e4bdec5
출처 데이터셋
uspto-grants-2005_06
특허 번호
US06903085B1

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