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

HRID 246448
ノート
印刷プレビュー

反応式

HRID 246448 の反応式
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[C:10]([C:18]2[N:19]=[C:20]3[C:26]([C:27]([NH:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:25][N:24](COCC[Si](C)(C)C)[C:21]3=[N:22][CH:23]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[C:10]([C:18]2[N:19]=[C:20]3[C:26]([C:27]([NH:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:25][NH:24][C:21]3=[N:22][CH:23]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712800812-(1-benzyl-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 712799822-(1-benzyl-6-chloro-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 115.9%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

2-(1-Benzyl-6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 151 μmol) was dissolved in dichloromethane (25 mL) and to this was added trifluoroacetic acid (1.72 g, 1.17 mL, 15.1 mmol). The mixture was stirred for 4 h then concentrated in vacuo. The residue was diluted in dichloromethane and re-concentrated again, then suspended in dichloromethane and ethylenediamine (682 mg, 0.766 mL, 11.3 mmol) added. The mixture was stirred for 15 h then concentrated in vacuo. The residue was triturated with water and the solid collected by filtration and dried. The solid was adsorbed onto silica gel and purified by chromatography (silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, 15 min gradient) to give 2-(1-benzyl-6-chloro-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (78 mg, 175 μmol, quantitative) as a pale yellow powder. MS (M−H)−=443; 1H NMR (DMSO-d6) δ: 12.84 (br. s., 1H), 9.05-9.13 (m, 1H), 8.37-8.50 (m, 2H), 8.08 (d, J=1.1 Hz, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.23-7.38 (m, 6H), 5.79 (s, 2H), 4.20 (dq, J=13.6, 6.7 Hz, 1H), 1.30 (d, J=6.4 Hz, 6H).

後処理

  1. concentrationthen concentrated in vacuo
  2. additionThe residue was diluted in dichloromethane
  3. concentrationre-concentrated again
  4. stirringThe mixture was stirred for 15 h
  5. concentrationthen concentrated in vacuo
  6. customThe residue was triturated with water
  7. filtrationthe solid collected by filtration
  8. customdried
  9. custompurified by chromatography (silica, SiliCycle 25 g cartridge, 0-5% methanol in dichloromethane, 15 min gradient)

出典と根拠

ORDレコード
ord-50cc1e2234064989b2d820ca0c57da58
出典データセット
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08658646B2

反応ノート

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