Sodium hydride → 2-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-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

HRID 246045Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246045
[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+].[CH3:43][C:44]1([CH3:55])[O:48][CH:47]([CH2:49]OS(C)(=O)=O)[CH2:46][O:45]1>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]([CH2:49][CH:47]5[CH2:46][O:45][C:44]([CH3:55])([CH3:43])[O:48]5)[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 15570840(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl methanesulfonateHCID 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 712889132-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

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 (see Example 23, 120 mg, 0.21 mmol) was dissolved in DMF (1.3 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 12 mg, 0.31 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then a solution of methanesulfonic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (131 mg, 0.62 mmol) in DMF (0.5 ml) was added. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for 48 h. The reaction mixture was quenched with water and extracted with ethyl acetate (2×). The combined organic layers were washed with water, sat LiCl, and brine then dried over MgSO4 and concentrated to give 2-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-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 as a light brown viscous oil which was used without further purification.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 0° C. for 1 h
  2. waitat room temperature for 48 h
  3. customThe reaction mixture was quenched with water
  4. extractionextracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with water
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-7672f2c30f3348248acf7d4ab566a5f0
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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