Nitrogen → (2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester

HRID 71714

Reaktionsgleichung

Reaktionsgleichung von HRID 71714
[CH3:1][O:2][C:3](=[O:28])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[Si:29]([C:33]#[CH:34])([CH3:32])([CH3:31])[CH3:30].C(N(CC)CC)C.N#N>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:1][O:2][C:3](=[O:28])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([C:34]#[C:33][Si:29]([CH3:32])([CH3:31])[CH3:30])=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Komponenten

8

Edukt 4

HCID 947NitrogenHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 66620141Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamate

Produkt 1

HCID 66619941(2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl esterAusbeute 59,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of (1-{2-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (5.00 g, 11.1 mmol), TMS-acetylene (7.90 mL, 55.5 mmol) and triethylamine (4.64 mL, 33.3 mmol) in DMF (56 mL) was degassed with N2 gas for 20 minutes. To the degassed solution was added Pd(PPh3)4 (1.28 g, 1.11 mmol) and CuI (106 mg, 0.56 mmol). The pressure flask was sealed then heated at 80° C. overnight. After cooling to room temperature, the reaction was concentrated then diluted with EtOAc and washed with water. The aqueous phase was back-extracted two times then the organic phases were combined and dried over Na2SO4. After concentration, the crude material was purified by silica gel chromatography (10-80% EtOAc-hexanes gradient) to afford (2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester (3.08 g, 6.60 mmol, 59% yield). LCMS-ESI+: calc'd for C25H35N4O3Si: 467.3 (M+H+). Found: 467.1 (M+H+).

Aufarbeitung

  1. customThe pressure flask was sealed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction was concentrated
  4. additionthen diluted with EtOAc
  5. washwashed with water
  6. extractionThe aqueous phase was back-extracted two times
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe crude material was purified by silica gel chromatography (10-80% EtOAc-hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-23627eed5e3843a1b0937ee60757ea25
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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