Isopropylamine → 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246109노트

반응식

HRID 246109 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[C:4]([F:32])[CH:3]=1.F[B-](F)(F)F.[N:38]1(OC(N(C)C)=[N+](C)C)[C:42]2[CH:43]=CC=C[C:41]=2N=N1.C(N(CC)C(C)C)(C)C.C(N)(C)C>C(#N)C.C(OCC)(=O)C.O>[CH:42]([NH:38][C:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=4[F:32])[N:8]([CH3:11])[N:7]=3)[N:13]=2)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])[CH:19]=1)=[O:22])([CH3:43])[CH3:41]

참가 물질

8

반응물 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712800452-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 712797082-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide수율 72%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

2-(6-Chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (59 mg, 0.124 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (60 mg, 0.186 mmol), N,N-diisopropylethylamine (0.11 ml, 0.62 mmol) and isopropylamine (11 ul, 0.124 mmol) were added together in acetonitrile (1.3 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 (ethyl acetate/hexanes) to give 46 mg (72%) of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide. (M+H)+=517.

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 (ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-b56b499c544545dfaebb1d6ebc9503ef
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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