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

HRID 246444ノート

反応式

HRID 246444 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-4a6a42717b754ffb8b38c328f18dd438
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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