Ethylenediamine → HCID 71279444, compound

HRID 246441Notes

Reaction equation

HRID 246441 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71279835HCID 71279835, compound

Product 1

HCID 71279444HCID 71279444, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (140 mg, 273 μmol) in dichloromethane (5 mL) was added trifluoroacetic acid (3.11 g, 2.1 mL, 27.3 mmol) at 20° C. After 6 h, the mixture was concentrated in vacuo. The residue was diluted with dichloromethane and concentrated again. The residue was then suspended in dichloromethane (5 mL) and ethylenediamine (1.23 g, 1.38 mL, 20.5 mmol) added. The mixture was stirred for 15 h, then concentrated in vacuo. The residue was triturated with water and the solid obtained by filtration. Purification by chromatography (silica, 25 g pre-packed SiliCycle cartridge, 0-5% methanol in dichloromethane gradient increasing over 15 min) gave N-tert-butyl-2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (63 mg, 165 μmol, 60%) as a pale yellow powder. MS (M+Na)+=405; 1H NMR (CDCl3) δ: 11.84 (br. s., 1H), 9.05 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 8.14 (d, J=3.4 Hz, 1H), 7.96 (s, 1H), 7.39 (d, J=1.5 Hz, 1H), 7.08 (dd, J=8.5, 1.7 Hz, 1H), 4.04 (s, 3H), 1.48 (s, 9H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additionThe residue was diluted with dichloromethane
  3. concentrationconcentrated again
  4. concentrationconcentrated in vacuo
  5. customThe residue was triturated with water
  6. customthe solid obtained by filtration
  7. customPurification
  8. temperatureby chromatography (silica, 25 g pre-packed SiliCycle cartridge, 0-5% methanol in dichloromethane gradient increasing over 15 min)

Sources & evidence

ORD record
ord-cda46c075d974793a9ed136978275fb6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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