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

HRID 246454
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HRID 246454 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]3[N:19]=[C:20]4[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]4=[N:22][CH:23]=3)=[N:7][N:8]2[CH2:11][C:12]2[N:13]([CH3:17])[CH:14]=[CH:15][N:16]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClC(Cl)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]3[N:19]=[C:20]4[C:26]([C:27]([NH:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:25][NH:24][C:21]4=[N:22][CH:23]=3)=[N:7][N:8]2[CH2:11][C:12]2[N:13]([CH3:17])[CH:14]=[CH:15][N:16]=2)=[CH:4][CH:3]=1
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참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 712799222-(6-chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

생성물 1

HCID 712793692-(6-chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 106%

시약·촉매·용매 1

HCID 63651,1-Dichloroethane
용매

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온도
80 °C

실험 절차

2-(6-Chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (106 mg, 183 μmol) was dissolved in dichloroethane (10 mL). To this mixture was added trifluoroacetic acid (2.09 g, 1.41 mL, 18.3 mmol) and the mixture was heated to 80° C. After 15 h, the mixture was concentrated in vacuo. The residue was dissolved in 60:20:1 dichloromethane:methanol:ammonium hydroxide (10 mL). After 2 h the mixture was concentrated in vacuo, then purified by chromatography (silica, Analogix 40 g, 0-5% methanol in dichloromethane, over 15 min) to give 2-(6-chloro-1-((1-methyl-1H-imidazol-2-yl)methyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 194 μmol, 106%) as a yellow powder. MS (M+H)+=449; 1H NMR (CDCl3) δ: 11.90-12.06 (m, 1H), 8.97-9.07 (m, 1H), 8.27-8.35 (m, 1H), 8.11-8.17 (m, 1H), 7.95-8.05 (m, 1H), 7.72-7.82 (m, 1H), 7.05-7.13 (m, 1H), 6.94-7.03 (m, 1H), 6.81-6.92 (m, 1H), 5.69-5.83 (m, 2H), 4.17-4.38 (m, 1H), 3.72 (s, 3H), 1.24 (d, J=6.4 Hz, 6H).

후처리

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in 60:20:1 dichloromethane
  3. concentrationAfter 2 h the mixture was concentrated in vacuo
  4. custompurified by chromatography (silica, Analogix 40 g, 0-5% methanol in dichloromethane, over 15 min)

출처 및 근거

ORD 기록
ord-bd298d76833e4a5d864bad97f4aa004a
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658646B2

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