Sodium hydride → 2-[6-Chloro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide

HRID 246257Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246257
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[NH:23][N:22]=4)[N:19]=3)[N:14]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:13]=2)=[O:11])[CH3:8])[CH:2]=1.[H-].[Na+].Br[CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>CN(C=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[N:23]([CH2:42][CH2:43][N:44]5[CH2:49][CH2:48][O:47][CH2:46][CH2:45]5)[N:22]=4)[N:19]=3)[N:14]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:37])([CH3:36])[CH3:38])[CH:13]=2)=[O:11])[CH3:8])[CH:2]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 15021014-(2-Bromoethyl)morpholineHCID 712883932-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide

Produkt 1

HCID 712884332-[6-Chloro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amideAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-(6-Chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide (100 mg, 0.18 mmol) was combined with DMF (2 mL) at 0° C. to give a yellow solution. Sodium hydride (60% in mineral oil, 22 mg, 0.55 mmol) was added and the reaction was stirred at 0° C. for 10 min. 4-(2-Bromoethyl)morpholine hydrocholoride (63 mg, 0.27 mmol) was added and the reaction was stirred at 0° C. for 30 min then warmed to room temperature and stirred for 2 h. The reaction mixture was quenched with 5 mL of brine and 10 mL of water and extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with water and brine then dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-10% methanol in dichloromethane) to afford 40 mg (33%) of 2-[6-chloro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=662.

Aufarbeitung

  1. customto give a yellow solution
  2. stirringthe reaction was stirred at 0° C. for 30 min
  3. temperaturethen warmed to room temperature
  4. stirringstirred for 2 h
  5. customThe reaction mixture was quenched with 5 mL of brine and 10 mL of water
  6. extractionextracted with ethyl acetate (2×30 mL)
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialthen dried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by silica gel chromatography (0-10% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-98a9bb8db3884720a1d27c5d171b03e6
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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