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Isopropylamine → 2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246113
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HRID 246113 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16]3[N:17]=[C:18]4[C:24]([C:25](O)=[O:26])=[CH:23][N:22]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:19]4=[N:20][CH:21]=3)=[N:7][N:8]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[C:4]([F:36])[CH:3]=1.F[B-](F)(F)F.[N:42]1(OC(N(C)C)=[N+](C)C)[C:46]2[CH:47]=CC=C[C:45]=2N=N1.C(N(CC)C(C)C)(C)C.C(N)(C)C>C(#N)C.C(OCC)(=O)C.O>[CH:46]([NH:42][C:25]([C:24]1[C:18]2[C:19](=[N:20][CH:21]=[C:16]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=4[F:36])[N:8]([CH2:11][CH2:12][N:13]([CH3:14])[CH3:15])[N:7]=3)[N:17]=2)[N:22]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:35])[CH3:33])[CH:23]=1)=[O:26])([CH3:47])[CH3:45]
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참가 물질

8

반응물 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712800772-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71280218
2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide
수율 65%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (50 mg, 0.094 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (45 mg, 0.14 mmol), N,N-diisopropylethylamine (0.08 ml, 0.47 mmol) and isopropylamine (10 ul, 0.11 mmol) were added together in acetonitrile (1 ml). The reaction was stirred at room temperature for 18 h then water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 35 mg (65%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted twice more with ethyl acetate
  3. washThe combined organic layers were washed with sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. customAfter evaporation
  6. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-dd9c6b7a55ff4bff9c5b215a2a023b0c
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658646B2

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