Ethylenediamine → 2-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246444Notes

Reaction equation

HRID 246444 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][N:17](COCC[Si](C)(C)C)[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][NH:17][C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712803652-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712796942-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.080 g, 165 μmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1.88 g, 1.27 mL, 16.5 mmol). The reaction mixture was stirred for 4 h, then was concentrated in vacuo. The residue was diluted with dichloromethane and concentrated in vacuo again, then was suspended in dichloromethane and ethylenediamine (743 mg, 0.835 mL, 12.4 mmol) added. After 15 h the mixture was concentrated, triturated with water and the solid obtained by filtration was dried and purified by chromatography (silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, gradient over 15 min) to give 2-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (24 mg, 67.0 μmol, 41%) as a pale yellow powder. MS (M+Na)+=377; 1H NMR (DMSO-d6) δ: 13.16 (br. s, 1H), 12.39 (br. s, 1H), 9.12 (s, 1H), 8.39 (d, J=8.7 Hz, 1H), 8.17 (d, J=2.6 Hz, 1H), 8.10 (d, J=7.9 Hz, 1H), 7.53 (s, 1H), 7.09 (dd, J=9.1, 1.0 Hz, 1H), 4.18-4.41 (m, 1H), 1.31 (d, J=6.4 Hz, 6H)

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThe residue was diluted with dichloromethane
  3. concentrationconcentrated in vacuo again
  4. concentrationAfter 15 h the mixture was concentrated
  5. customtriturated with water
  6. customthe solid obtained by filtration
  7. customwas dried
  8. custompurified by chromatography (silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, gradient over 15 min)

Sources & evidence

ORD record
ord-4a6a42717b754ffb8b38c328f18dd438
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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