Formaldehyde → (4-Benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanone

HRID 1097847ノート

反応式

HRID 1097847 の反応式
Cl.[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH2:29][CH2:30][NH:31][CH3:32])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[CH2:33](N(CC)CC)C.C=O.[C:42]([BH3-])#N.[Na+]>CO>[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[CH:26]=[CH:25][C:24]([Cl:28])=[CH:23][C:22]=4[N:21]4[CH2:29][CH2:30][N:31]([CH3:42])[CH2:32][C:20]=34)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1

参加物

7

反応物 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 25001181(4-Benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-methylamino-ethyl)-1H-indol-3-yl]-methanone hydrochloride

生成物 2

HCID 25001183(4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indol-3-yl]-methanone収率 22%HCID 25001184(4-Benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanone収率 60%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

A mixture of 0.20 g (0.41 mmol) (4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-methylamino-ethyl)-1H-indol-3-yl]-methanone hydrochloride, 0.057 ml (0.41 mmol) triethylamine and 0.10 g (3.3 mmol) paraformaldehyde in 4 ml methanol was heated at reflux for 7 h. After cooling to 0° C. 0. were added 052 g (0.82 mmol) sodium cyanoborohydride. The cooling bath was removed and the reaction mixture was stirred at room temperature for 16 h. Quenching with 1 M aqueous sodium hydroxide solution was followed by extraction with two portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Flash chromatography gave 0.040 g (22%) (4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indol-3-yl]-methanone as a white solid (ES-MS m/e (%): 451 (M+H+, 100)) and 0.11 g (60%) (4-benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanone as a white solid (ES-MS m/e (%): 449 (M+H+, 100)).

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 7 h
  3. customThe cooling bath was removed
  4. customQuenching with 1 M aqueous sodium hydroxide solution
  5. extractionwas followed by extraction with two portions of ethyl acetate
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-2b073df6e4524f10bcda1265b75182b1
出典データセット
uspto-grants-2012_03
特許番号
US08143281B2

反応ノート

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