Tetrahydrofuran → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine

HRID 323230

Reaktionsgleichung

Reaktionsgleichung von HRID 323230
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[NH:34][C:33]4[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=4[N:31]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([CH3:20])[CH:14]=2)[CH2:9]1)=[O:7].[O:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(OCCCl)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.CO>[CH3:45][O:44][C:40]1[CH:39]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[N:31]([CH2:48][CH2:47][O:46][CH2:50][CH3:49])[C:32]4[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=4[N:34]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([CH3:20])[CH:14]=2)[CH2:9]1)=[O:7]

Komponenten

8

Edukt 4

HCID 8028TetrahydrofuranHCID 12341Ethane, 1-chloro-2-ethoxy-HCID 3251421Potassium bis(trimethylsilyl)amideHCID 99388361-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine

Produkt 1

HCID 98313851-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine (0.46 g, 0.76 mmol) and tetrahydrofuran (35 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (2.1 mL, 0.5 M in toluene, 1.05 mmol). After 20 minutes, warm to ambient temperature. Add tetrabutylammonium bromide (0.21 g, 0.65 mmol) and 2-chloroethyl ethyl ether (1 mL). Heat to reflux. After 2 days, cool the reaction mixture and dilute with dichloromethane. Extract with water and saturated aqueous solution of sodium chloride. Concentrate the separated organic layer in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 28% methanol/0.7% concentrated aqueous ammonia/ethyl acetate to give the title compound: Rf=0.26 (silica gel, 30% methanol/ethyl acetate).

Aufarbeitung

  1. temperaturewarm to ambient temperature
  2. temperatureHeat to reflux
  3. waitAfter 2 days
  4. temperaturecool the reaction mixture
  5. extractionExtract with water and saturated aqueous solution of sodium chloride
  6. concentrationConcentrate the separated organic layer in vacuo
  7. customto give a residue

Quellen und Nachweise

ORD-Eintrag
ord-5161eb6ba0934903a482e76525eb3e59
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06211199B1

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