Benzaldehyde → HCID 117667673、化合物

HRID 1526272ノート

反応式

HRID 1526272 の反応式
Cl[C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9].[NH2:33][CH2:34][CH2:35][N:36]([CH3:44])[C:37](=[O:43])OC(C)(C)C.[CH:45](N(C(C)C)CC)(C)[CH3:46].C(=O)C1C=CC=CC=1>CN(C)C=O.CN1CCCC1=O>[C:37]([N:36]([CH3:44])[CH2:35][CH2:34][NH:33][C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:21][CH2:22][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:24][CH2:25]3)=[CH:16][CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9])(=[O:43])[CH:45]=[CH2:46]

参加物

7

反応物 4

HCID 240BenzaldehydeHCID 81531DiisopropylethylamineHCID 2756424N-Boc-N-methylethylenediamineHCID 885697085-Chloro-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide

生成物 1

HCID 117667673HCID 117667673、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
140 °C

実験手順

A mixture of 5-chloro-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (21 mg), tert-butyl (2-aminoethyl)methylcarbamate (31 mg), diisopropylethylamine (16 μL), and N-methylpyrrolidone (0.3 mL) was stirred at 140° C. for 2 hours and a half. To the reaction mixture was added PS-benzaldehyde (Biotage, 150 mg) at room temperature, N,N-dimethylformamide (1 mL) was added thereto, followed by stirring for 2 hours, and the insoluble matter was filtered. The filtrate was evaporated under reduced pressure and the obtained residue were added methanol (0.5 mL) and a 4 M hydrogen chloride-dioxane solution (0.45 mL), followed by stirring at room temperature for 8 hours. The solvent was evaporated under reduced pressure, and to the obtained residue were added tetrahydrofuran (0.9 mL) and a saturated aqueous sodium hydrogen carbonate solution (1 mL), followed by stirring at room temperature. Acryloyl chloride (8 μL) and tetrahydrofuran (0.1 mL) were added thereto at room temperature, followed by stirring for 4 hours. The reaction mixture was extracted with chloroform. The solvent of the organic phase was evaporated under reduced pressure and the obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution) to obtain 5-({2-[acryloyl (methyl)amino]ethyl}amino)-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (1 mg).

後処理

  1. stirringby stirring for 2 hours
  2. filtrationthe insoluble matter was filtered
  3. customThe filtrate was evaporated under reduced pressure
  4. additionthe obtained residue were added methanol (0.5 mL)
  5. stirringby stirring at room temperature for 8 hours
  6. customThe solvent was evaporated under reduced pressure
  7. additionto the obtained residue were added tetrahydrofuran (0.9 mL)
  8. stirringby stirring at room temperature
  9. additionAcryloyl chloride (8 μL) and tetrahydrofuran (0.1 mL) were added
  10. customat room temperature
  11. stirringby stirring for 4 hours
  12. extractionThe reaction mixture was extracted with chloroform
  13. customThe solvent of the organic phase was evaporated under reduced pressure
  14. customthe obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution)

出典と根拠

ORDレコード
ord-b4cdfe82c8e844b9a7be76e2da577c50
出典データセット
uspto-grants-2015_07
特許番号
US09085540B2

反応ノート

読み込み中…