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Sodium hydride → 3'-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2',3',4',5'-tetrahydro-1H-[2,4']biimidazolyl-1'-carboxylic acid tert-butyl ester

HRID 71764
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 71764
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH:13]([C:15]2[NH:16][CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35]=[C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:54])[CH:45]([NH:49][C:50]([O:52][CH3:53])=[O:51])[CH:46]([CH3:48])[CH3:47])[NH:37][CH:38]=5)=[CH:30][CH:29]=4)=[CH:22][CH:21]=3)[N:19]=2)[N:12]([C:55](=[O:65])[CH:56]([NH:60][C:61]([O:63][CH3:64])=[O:62])[CH:57]([CH3:59])[CH3:58])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:66][Si:67]([CH3:74])([CH3:73])[CH2:68][CH2:69][O:70][CH2:71]Cl>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][CH:13]([C:15]2[N:16]([CH2:71][O:70][CH2:69][CH2:68][Si:67]([CH3:74])([CH3:73])[CH3:66])[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35]=[C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:54])[CH:45]([NH:49][C:50]([O:52][CH3:53])=[O:51])[CH:46]([CH3:48])[CH3:47])[N:37]([CH2:71][O:70][CH2:69][CH2:68][Si:67]([CH3:74])([CH3:73])[CH3:66])[CH:38]=5)=[CH:30][CH:29]=4)=[CH:22][CH:21]=3)[N:19]=2)[N:12]([C:55](=[O:65])[CH:56]([NH:60][C:61]([O:63][CH3:64])=[O:62])[CH:57]([CH3:58])[CH3:59])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
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Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178502176HCID 178502176, Verbindung

Produkt 1

HCID 866488803'-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2',3',4',5'-tetrahydro-1H-[2,4']biimidazolyl-1'-carboxylic acid tert-butyl ester
Ausbeute 156,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Sodium hydride (60% in mineral oil, 27 mg, 0.55 mmol) was added to a solution of 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid tert-butyl ester (248 mg, 0.23 mmol) in dimethylformamide (8 mL) under an atmosphere of nitrogen at 0° C. After 15 minutes 2-(trimethylsilyl)ethoxymethyl chloride (107.5 μL, 0.48 mmol) was added and the reaction was allowed to warm to ambient temperature. After 2 hours the solvent was removed under reduced pressure. The residue was taken up in dichloromethane (50 mL) washed with water (20 mL), and dried over sodium sulfate and filtered. The solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid tert-butyl ester (410 mg, 0.36 mmol). C58H85N9O10Si2 calculated 1123.6 observed [M+1]+ 1124.7; rt=3.10 min.

Aufarbeitung

  1. customAfter 2 hours the solvent was removed under reduced pressure
  2. washwashed with water (20 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. customthe solvent was removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-826847c0173242df838c268122aef4fd
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08822430B2

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