Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-pyrazol-1-yl-ethyl)-amide

HRID 246122노트

반응식

HRID 246122 반응식
FC(F)(F)C(O)=O.[CH3:8][C@@H:9]([NH2:16])[CH2:10][N:11]1[CH:15]=[CH:14][CH:13]=[N:12]1.[F:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([C:28]3[N:29]=[C:30]4[C:36]([C:37](O)=[O:38])=[CH:35][N:34]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[C:31]4=[N:32][CH:33]=3)=[N:23][N:24]2[CH3:27])=[CH:20][CH:19]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(#N)C.C(OCC)(=O)C.O>[CH3:8][C@@H:9]([NH:16][C:37]([C:36]1[C:30]2[C:31](=[N:32][CH:33]=[C:28]([C:22]3[C:21]4[C:25](=[CH:26][C:18]([F:17])=[CH:19][CH:20]=4)[N:24]([CH3:27])[N:23]=3)[N:29]=2)[N:34]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[CH:35]=1)=[O:38])[CH2:10][N:11]1[CH:15]=[CH:14][CH:13]=[N:12]1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71279935(R)-1-methyl-2-pyrazol-1-yl-ethylamine trifluoroacetate

생성물 1

HCID 712861932-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-pyrazol-1-yl-ethyl)-amide수율 81%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

(R)-1-Methyl-2-pyrazol-1-yl-ethylamine trifluoroacetate (crude from Step 4) was dissolved in acetonitrile (1.8 ml) to which was then added 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 0.18 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (87 mg, 0.27 mmol) and N,N-diisopropylethylamine (0.16 ml, 0.91 mmol). The reaction was stirred at room temperature for 18 h and then water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted three times 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 afford 89 mg (81%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-pyrazol-1-yl-ethyl)-amide.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted three times 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-2761b53bce4645a1b4a027d42b1c84c6
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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