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 246092ノート

反応式

HRID 246092 の反応式
[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

参加物

7

反応物 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

生成物 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]-amide収率 58%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-12a189439cac43c28bd780466a3ac4c2
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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