Sodium Azide → 1-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(4-(1H-tetrazol-5-yl)butyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

HRID 637159Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 637159
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([O:48][CH3:49])[C:45]=1[O:46][CH3:47])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[N:32]([CH2:33][CH2:34][CH2:35][CH2:36][C:37]#[N:38])[C:31]4[CH:39]=[CH:40][CH:41]=[CH:42][C:30]=4[N:29]=3)[CH2:23][CH2:22]2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9]1)=[O:7].[N-:50]=[N+:51]=[N-:52].[Na+].Cl.C([NH+](CC)CC)C.CO.ClCCl>CN1CCCC1=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([O:48][CH3:49])[C:45]=1[O:46][CH3:47])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]3[N:32]([CH2:33][CH2:34][CH2:35][CH2:36][C:37]4[NH:52][N:51]=[N:50][N:38]=4)[C:31]4[CH:39]=[CH:40][CH:41]=[CH:42][C:30]=4[N:29]=3)[CH2:23][CH2:22]2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:9]1)=[O:7]

Komponenten

6

Edukt 4

HCID 33557Sodium AzideHCID 184649071-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(4-cyanobutyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidineHCID 21226129Dichloromethane methanolHCID 21900368Triethylammonium hydrochloride

Produkt 1

HCID 1784926461-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(4-(1H-tetrazol-5-yl)butyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-cyanobutyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (0.45 g, 0.67 mmol), sodium azide (0.13 g, 2.04 mmol), and triethylammonium hydrochloride (0.14 g, 1.03 mmol) in N-methylpyrrolidinone (6 mL). Heat to 150° C. After 4 hours, cool to ambient temperature and partition the reaction mixture between water and ethyl acetate. Separate the layers and extract the aqueous layer three times with ethyl acetate. Adjust the pH of the aqueous layer to about 1 using a 1 M aqueous hydrochloric acid solution. The aqueous layer is again extracted three times with ethyl acetate, and twice with dichloromethane. The aqueous layer is saturated with sodium chloride and again extracted four times with dichloromethane. Combine the organic layers, dry over MgSO4, filter, and evaporate in vacuo to give residue. Chromatograph the residue on silica gel eluting with 20% methanol/dichloromethane to give the title compound: Rf=0.33 (silica gel, 20% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Aufarbeitung

  1. temperaturecool to ambient temperature
  2. custompartition the reaction mixture between water and ethyl acetate
  3. customSeparate the layers
  4. extractionextract the aqueous layer three times with ethyl acetate
  5. extractionThe aqueous layer is again extracted three times with ethyl acetate
  6. extractionagain extracted four times with dichloromethane
  7. dry with materialdry over MgSO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give residue

Quellen und Nachweise

ORD-Eintrag
ord-e17592c5c5394fa4bd670664f9d82ebc
Quelldatensatz
uspto-grants-2001_02
Patentnummer
US06194406B1

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