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

HRID 246446Notes

Reaction equation

HRID 246446 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]3[N:14]=[C:15]4[C:21]([C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])=[CH:20][N:19](COCC[Si](C)(C)C)[C:16]4=[N:17][CH:18]=3)=[N:7][N:8]2[CH2:11][CH3:12])=[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:13]3[N:14]=[C:15]4[C:21]([C:22]([NH:24][CH:25]([CH3:26])[CH3:27])=[O:23])=[CH:20][NH:19][C:16]4=[N:17][CH:18]=3)=[N:7][N:8]2[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712804172-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712794512-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 91.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(6-Chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (78 mg, 152 μmol) was dissolved in dichloromethane and to this was added trifluoroacetic acid (1.73 g, 1.17 mL, 15.2 mmol). The mixture was stirred for 4 h then concentrated en vacuo. The residue was diluted in dichloromethane and re-concentrated, and finally diluted again in dichloromethane and to this was added ethylenediamine (685 mg, 770 μL, 11.4 mmol). After 15 h the mixture was concentrated in vacuo, triturated with water and the collected solid was filtered and dried. The solid was purified by chromatography (Silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, 15 min gradient) to give 2-(6-chloro-1-ethyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (53 mg, 138 μmol, 91.1%) as a pale yellow powder. MS (M+H)+=383; 1H NMR (CDCl3) δ: 11.74 (br. s., 1H), 9.11-9.15 (m, 1H), 8.41 (d, J=8.7 Hz, 1H), 8.20 (d, J=3.0 Hz, 1H), 8.14 (d, J=7.9 Hz, 1H), 7.44 (s, 1H), 7.15 (dd, J=8.5, 1.3 Hz, 1H), 4.28-4.48 (m, 3H), 1.53 (t, J=7.2 Hz, 3H), 1.33 (d, J=6.4 Hz, 6H)

Workup

  1. concentrationthen concentrated en vacuo
  2. additionThe residue was diluted in dichloromethane
  3. concentrationre-concentrated
  4. additionfinally diluted again in dichloromethane
  5. concentrationAfter 15 h the mixture was concentrated in vacuo
  6. customtriturated with water
  7. filtrationthe collected solid was filtered
  8. customdried
  9. customThe solid was purified by chromatography (Silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, 15 min gradient)

Sources & evidence

ORD record
ord-90a695d641a340a89c5d322804e9d9ec
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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