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

HRID 246110ノート

反応式

HRID 246110 の反応式
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([Cl:26])=[CH:22][C:23]=4[F:25])[N:18]([CH3:27])[N:17]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([Cl:26])=[CH:22][C:23]=4[F:25])[N:18]([CH3:27])[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712797082-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

生成物 1

HCID 712802492-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide収率 98%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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 (46 mg, 0.09 mmol) was dissolved in dichloromethane (1.2 ml) and cooled in ice bath. Trifluoroacetic acid (0.6 ml) was slowly added and the reaction was stirred at room temperature for 2 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1 ml). Ethylenediamine (0.36 ml, 5.3 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 diethyl ether and ethyl acetate and set aside. The organic filtrate was separated, washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was combined with the precipitate collected above. The solids were dried under high vacuum to afford 34 mg (98%) of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide. MS: (M+H)+=387; mp=347-349° C. 1H NMR (300 MHz, DMSO-d6) δ: 9.01 (s, 1H), 8.42 (s, 1H), 8.22-8.33 (m, 1H), 7.88 (s, 1H), 7.20-7.32 (m, 1H), 4.13-4.30 (m, 1H), 4.18 (s, 3H), 1.24 (d, J=6.4 Hz, 6H).

後処理

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane (1 ml)
  4. stirringthe mixture was stirred for 18 h
  5. filtrationThe resulting precipitate was filtered off
  6. washrinsed with water diethyl ether and ethyl acetate
  7. customThe organic filtrate was separated
  8. washwashed with sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. customAfter evaporation
  11. customcollected above
  12. customThe solids were dried under high vacuum

出典と根拠

ORDレコード
ord-a8d6ed23c42748a2bc96f49e814cd594
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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