2-Methyl-2H-indazol-6-amine → 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide

HRID 602426ノート

反応式

HRID 602426 の反応式
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH2:11])[CH:7]=[CH:8]2)=[N:3]1.C[Al](C)C.C[O:17][C:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][C:20]=1[NH:25][CH2:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([Cl:33])[CH:28]=1>ClCCCl>[Cl:33][C:29]1[CH:28]=[C:27]([CH2:26][NH:25][C:20]2[N:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18]([NH:11][C:6]2[CH:7]=[CH:8][C:9]3[C:4]([CH:5]=2)=[N:3][N:2]([CH3:1])[CH:10]=3)=[O:17])[CH:32]=[CH:31][N:30]=1

参加物

5

反応物 3

HCID 5902202-Methyl-2H-indazol-6-amineHCID 16682925TrimethylaluminumHCID 586749472-[(2-Chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester

生成物 1

HCID 586749502-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide収率 77.2%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

反応条件

温度
100 °C

実験手順

To a stirred and chilled (0° C.) suspension of 2-methyl-2H-indazol-6-ylamine (1.52 g) in DCE (6 mL), under nitrogen, was added trimethylaluminium (2M solution in toluene, 5 mL, 9.37 mmol). This mixture was added dropwise to a stirred and chilled (0° C.) solution of 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester (1.45 g, 5.21 mmol) in DCE (14.7 mL). The mixture was heated at 100° C. for 2 hours before cooling to room temperature and quenching by pouring into aqueous sodium-potassium tartrate solution. The mixture was extracted with EtOAc and the combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine, dried and concentrated in vacuo to give 2-[(2-chloro-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-nicotinamide (1.58 g); 1H-NMR (300 MHz, d6-DMSO) 10.26 (1H, s), 8.40 (1H, t), 8.28 (1H, d), 8.25 (1H, s), 8.06-8.12 (3H, m), 7.62 (1H, d), 7.35 (1H, s), 7.30 (1H, unresolved dd), 7.27 (1H, unresolved dd), 6.68 (1H, dd), 4.67 (2H, d), 4.10 (3H, s).

後処理

  1. temperaturechilled
  2. additionThis mixture was added dropwise to
  3. stirringa stirred
  4. temperaturebefore cooling to room temperature
  5. customquenching
  6. additionby pouring into aqueous sodium-potassium tartrate solution
  7. extractionThe mixture was extracted with EtOAc
  8. washthe combined organic layers washed successively with dilute aqueous citric acid solution, dilute aqueous sodium hydrogen carbonate solution and brine
  9. customdried
  10. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ab16cb210a6e4970b5ee0826868b25da
出典データセット
uspto-grants-2011_03
特許番号
US07906533B2

反応ノート

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