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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-[2-methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-phenyl]-methanone

HRID 2230745
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반응식

HRID 2230745 반응식
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[N:15][N:14]=[C:13]2[S:17][CH3:18])=[CH:8][C:4]=1[C:5]([OH:7])=O.Cl.Cl.[CH2:21]([O:23][CH2:24][CH2:25][N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]=[C:27]1[N:35]1[CH2:41][CH2:40][CH2:39][N:38]([CH2:42][CH2:43][C@:44]2([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:48][CH2:47][NH:46][CH2:45]2)[CH2:37][CH2:36]1)[CH3:22].O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl>[CH2:21]([O:23][CH2:24][CH2:25][N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]=[C:27]1[N:35]1[CH2:41][CH2:40][CH2:39][N:38]([CH2:42][CH2:43][C@:44]2([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:48][CH2:47][N:46]([C:5]([C:4]3[CH:8]=[C:9]([N:12]4[CH:16]=[N:15][N:14]=[C:13]4[S:17][CH3:18])[CH:10]=[CH:11][C:3]=3[O:2][CH3:1])=[O:7])[CH2:45]2)[CH2:37][CH2:36]1)[CH3:22]
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참가 물질

7

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 184647022-Methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-benzoic acidHCID 701481071-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride

생성물 1

HCID 59902268
1-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-[2-methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-phenyl]-methanone
수율 17.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a mixture of 2-methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-benzoic acid (0.27 g, 0.42 mmol), 1-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride (0.23 g, 0.42 mmol), 1-hydroxybenzotriazole hydrate (0.068 g, 0.51 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.97 g, 0.51 mmol), add via syringe under argon anhydrous dichloromethane (15 mL). Add diisopropylethylamine (0.22 mL, 1.26 mmol) and stir at room temperature for 20 hours. Dilute with dichloromethane and wash twice with water. Wash with saturated NaHCO3 solution, dry (MgSO4) the organic phase, filter and concentrate to an oil. Purify the oil by flash chromatography (silica gel, 3.5×15.2 cm) eluting with dichloromethane and then with 10% methanol in dichloromethane. Concentrate the appropriate fractions to afford 0.051 g of the title compound, Rf=0.26 (silica gel, 10% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

후처리

  1. additionadd via syringe under argon anhydrous dichloromethane (15 mL)
  2. washwash twice with water
  3. washWash with saturated NaHCO3 solution
  4. dry with materialdry (MgSO4) the organic phase
  5. filtrationfilter
  6. concentrationconcentrate to an oil
  7. customPurify the oil by flash chromatography (silica gel, 3.5×15.2 cm)
  8. washeluting with dichloromethane
  9. concentrationConcentrate the appropriate fractions

출처 및 근거

ORD 기록
ord-25f6f960a2814cbebafb0ced7bc99a60
출처 데이터셋
uspto-grants-2002_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06423704B1

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