Sodium hydride → 2-[6-chloro-1-(2-methoxy-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyanoazetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 245836Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245836
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[NH:24][N:23]=4)[N:20]=3)[N:15]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].[H-].[Na+].Br[CH2:44][CH2:45][O:46][CH3:47]>CN(C=O)C>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:44][CH2:45][O:46][CH3:47])[N:23]=4)[N:20]=3)[N:15]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 712888432-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Produkt 1

HCID 712888472-[6-chloro-1-(2-methoxy-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyanoazetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

In a round-bottomed flask, 2-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (90 mg, 0.155 mmol) was dissolved in DMF (1 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 8 mg, 0.20 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then 1-bromo-2-methoxyethane (22 μl, 0.23 mmol) was added. The reaction mixture was stirred at 0° C. for 3 h and then at room temperature overnight. The reaction mixture was quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH) to afford 51 mg (52%) of 2-[6-chloro-1-(2-methoxy-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow foam.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 0° C. for 3 h
  2. customat room temperature
  3. customovernight
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with diethyl ether (2×)
  6. washThe combined organic layers were washed twice with water and once with brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-30f3838bdb5f44fe9d508755b0b0be84
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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