Water → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246092노트

반응식

HRID 246092 반응식
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:3]1.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:3]1

참가 물질

7

반응물 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861822-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

생성물 1

HCID 712882422-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide수율 58%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (54 mg, 0.09 mmol) was dissolved in dichloromethane (0.9 ml) and cooled in ice bath. Trifluoroacetic acid (0.45 ml) was slowly added and the reaction was stirred at room temperature for 2.5 h. The reaction was evaporated and the residue was suspended in dichloromethane (0.9 ml). Ethylenediamine (0.36 ml, 5.4 mmol) was added and the mixture was stirred for 18 h. Water and then ethyl acetate were added to the mixture. The resulting precipitate was filtered off, rinsed with water and dried under high vacuum to give 24 mg (58%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide. MS: (M+H)+=470; mp=269-271° C. 1H NMR (300 MHz, DMSO-d6) δ: 9.16 (s, 1H), 8.81-8.91 (m, 1H), 8.53-8.62 (m, 1H), 8.47 (d, J=2.0 Hz, 1H), 7.97 (s, 1H), 7.25-7.33 (m, 1H), 5.27-5.52 (m, 1H), 4.95-5.11 (m, 1H), 4.18 (s, 3H), 3.96-4.12 (m, 1H), 3.73-3.92 (m, 1H), 3.61-3.72 (m, 1H), 2.08-2.35 (m, 1H), 1.38-1.48 (m, 3H).

후처리

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. stirringthe mixture was stirred for 18 h
  4. filtrationThe resulting precipitate was filtered off
  5. washrinsed with water
  6. customdried under high vacuum

출처 및 근거

ORD 기록
ord-12a189439cac43c28bd780466a3ac4c2
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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