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

HRID 246265Notes

Reaction equation

HRID 246265 reaction equation
[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[NH:24][N:23]=3)[N:20]=2)[N:15]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[H-].[Na+].Cl.Br[CH2:44][CH2:45][N:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1>CN(C=O)C>[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:44][CH2:45][N:46]4[CH2:50][CH2:49][CH2:48][CH2:47]4)[N:23]=3)[N:20]=2)[N:15]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:39])[CH3:38])[CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 124407811-(2-Bromoethyl)pyrrolidine hydrochlorideHCID 712857502-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

Product 1

HCID 712883782-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amideYield 91%

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-methyl-2-pyridin-2-yl-ethyl)-amide (70 mg, 0.13 mmol) was combined with DMF (2 mL) at 0° C. to give a yellow solution. Sodium hydride (60% in mineral oil, 14 mg, 0.385 mmol) was added and the reaction was stirred at 0° C. for 10 min. 1-(2-Bromoethyl)pyrrolidine hydrochloride (41 mg, 0.19 mmol) was added and teh reaction was stirred at 0° C. for 30 min then warmed to room temperature. The reaction mixture was stirred for 2 h 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 residue was purified by silica gel chromatography (0-10% methanol in dichloromethane) to afford 75 mg (91%) of 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=643.

Workup

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

Sources & evidence

ORD record
ord-14360761cfe042eab2e596252171e170
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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