Ethylenediamine → 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

HRID 246266ノート

反応式

HRID 246266 の反応式
[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[N:15](COCC[Si](C)(C)C)[CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[NH:15][CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883782-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide

生成物 1

HCID 712883822-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide収率 43.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide (75 mg, 0.117 mmol) was combined with dichloromethane (1 mL) then trifluoroacetic acid (0.26 ml, 3.50 mmol) was added. After stirring for 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (1 mL) and ethylenediamine (0.23 ml, 3.50 mmol) was added and the reaction was stirred at room temperature for 20 min. The reaction mixture was concentrated in vacuo and the residue was triturated with water (2 mL). The precipitate was filtered, washed with water and dried to afford 26 mg (41%) of 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide (26 mg, 41%) as a yellow solid. MS: (M+H)+=513; 1H NMR (DMSO-d6) δ: 9.07 (s, 1H), 8.32-8.44 (m, 2H), 8.22 (d, J=8.3 Hz, 1H), 7.73 (d, J=9.8 Hz, 1H), 7.50-7.66 (m, 2H), 7.27 (d, J=7.8 Hz, 1H), 7.03-7.16 (m, 2H), 4.53-4.67 (m, 4H), 4.46 (s, 1H), 3.02-3.25 (m, 2H), 2.98 (t, J=6.5 Hz, 3H), 1.64 (br. s., 5H), 1.29 (d, J=6.5 Hz, 3H).

後処理

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  3. stirringthe reaction was stirred at room temperature for 20 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue was triturated with water (2 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

出典と根拠

ORDレコード
ord-7594e4ca97c74bc09894f3a4ecb8b896
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…