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

HRID 246444노트

반응식

HRID 246444 반응식
[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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-4a6a42717b754ffb8b38c328f18dd438
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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