Ethylenediamine → 2-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 245955Notes

Reaction equation

HRID 245955 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH:23]=4)[N:18]([CH3:33])[N:17]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([O:25][Si:26]([C:29]([CH3:30])([CH3:32])[CH3:31])([CH3:28])[CH3:27])[CH:23]=4)[N:18]([CH3:33])[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712796602-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

Product 1

HCID 712797692-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamideYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (100 mg, 0.168 mmol) was dissolved in dichloromethane (0.8 ml) and trifluoroacetic acid (0.52 ml, 6.75 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.8 ml) and ethylenediamine (0.68 ml, 10.1 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with ethyl acetate to afford 55 mg (70%) of 2-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a yellow powder.

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.8 ml)
  3. stirringThe yellow solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-59aea70cadff4e7f9adfa0b4410a3647
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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