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

HRID 245885

反応式

HRID 245885 の反応式
[CH3:1][C@H:2]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[N:12](COCC[Si](C)(C)C)[CH:11]=1)=[O:9])[C:3]([CH3:6])([CH3:5])[CH3:4].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][C@H:2]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[NH:12][CH:11]=1)=[O:9])[C:3]([CH3:6])([CH3:5])[CH3:4]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861832-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide

生成物 1

HCID 712881632-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide収率 68%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide (102 mg, 0.194 mmol) was dissolved in dichloromethane (0.9 ml) and trifluoroacetic acid (0.6 ml, 7.8 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.9 ml) and ethylenediamine (0.8 ml, 11.7 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 52 mg (64%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide as a light yellow powder. MS: (M+H)+=395; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.38 (br. s., 1H), 9.08 (s, 1H), 8.44 (s, 1H), 8.40 (dd, J=9.1, 5.3 Hz, 1H), 8.03 (d, J=9.8 Hz, 1H), 7.69 (dd, J=9.8, 1.9 Hz, 1H), 7.20 (td, J=9.1, 2.3 Hz, 1H), 4.15 (s, 3H), 4.09-4.19 (m, 1H), 1.26 (d, J=6.8 Hz, 3H), 0.93 (s, 9H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.9 ml)
  3. stirringThe yellow solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

出典と根拠

ORDレコード
ord-73179c4fe81d4d5ca82743830e3840d8
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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