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

HRID 246261Notes

Reaction equation

HRID 246261 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([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]([F: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:3][CH:2]=1.[H-].[Na+].Cl.Br[CH2:43][CH2:44][N:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>CN(C=O)C>[N:1]1[CH:2]=[CH:3][C:4]([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]([F:30])=[CH:27][CH:28]=5)[N:23]([CH2:43][CH2:44][N:45]5[CH2:50][CH2:49][O:48][CH2:47][CH2:46]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:5][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 129555404-(2-Bromoethyl)morpholine hydrochlorideHCID 712861042-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-4-yl-ethyl)-amide

Product 1

HCID 712884452-[6-Fluoro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-4-yl-ethyl)-amideYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-(6-Fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-4-yl-ethyl)-amide (100 mg, 0.19 mmol) was combined with DMF (2 mL) at 0° C. to give a yellow solution. Sodium hydride (60% in mineral oil, 23 mg, 0.56 mmol) was added and the reaction was stirred at 0° C. for 10 min. 4-(2-Bromoethyl)morpholine hydrochloride (55 mg, 0.28 mmol) was added and the reaction was stirred at 0° C. for 30 min then warmed to room temperature. The reaction mixture was stirred for 2 h at room temperature then 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 give 70 mg (58%) of 2-[6-fluoro-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-4-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=645.

Workup

  1. customto give a yellow solution
  2. stirringthe reaction was stirred at 0° C. for 30 min
  3. temperaturethen warmed to room temperature
  4. stirringThe reaction mixture was stirred for 2 h at room temperature
  5. customthen 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)

Sources & evidence

ORD record
ord-61d9e0a9fe7c4705a220ac3a04d9aba6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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