Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide

HRID 246559

Reaction equation

HRID 246559 reaction equation
[CH3:1][O:2][NH:3][C:4]([C:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]([CH3:25])[N:16]=3)[N:13]=2)[N:8](COCC[Si](C)(C)C)[CH:7]=1)=[O:5].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][O:2][NH:3][C:4]([C:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]([CH3:25])[N:16]=3)[N:13]=2)[NH:8][CH:7]=1)=[O:5]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 866779872-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide

Product 1

HCID 866779882-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amideYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide (53 mg, 113 μmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.4 mL, 5.19 mmol) at 20° C. After 2 h, the mixture was concentrated in vacuo. The residue was diluted with dichloromethane and concentrated again. The residue was then suspended in dichloromethane (2 mL) and ethylenediamine (0.4 mL, 5.92 mmol) added. The mixture was stirred for 1 h, then concentrated in vacuo. To the residue was added ethyl acetate and water. The organic layer was then washed with brine then dried (sodium sulfate), filtered and concentrated in vacuo. Purification by chromatography (silica, 25 g pre-packed SiliCycle cartridge, 40-80% EtOAc in hexane gradient increasing over 15 min) gave 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid methoxy-amide (45 mg, 0.39 μmol, 39%) as a light yellow powder. MS (M+H)+=341; 1H NMR (DMSO-d6) δ: 12.87 (br. s., 1H), 10.97 (s, 1H), 9.09 (s, 1H), 8.66 (dd, J=8.8, 5.3 Hz, 1H), 8.45 (s, 1H), 7.67 (d, J=9.8 Hz, 1H), 7.24 (t, J=9.3 Hz, 1H), 4.15 (s, 3H), 3.84 (s, 3H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additionThe residue was diluted with dichloromethane
  3. concentrationconcentrated again
  4. concentrationconcentrated in vacuo
  5. additionTo the residue was added ethyl acetate and water
  6. washThe organic layer was then washed with brine
  7. dry with materialthen dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification
  11. temperatureby chromatography (silica, 25 g pre-packed SiliCycle cartridge, 40-80% EtOAc in hexane gradient increasing over 15 min)

Sources & evidence

ORD record
ord-ab829e63a3ef4b8790ae0f2b177ddac9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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