1-Hydroxybenzotriazole → 1-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3-(fluoromethyl) piperazine, hydrochloride salt

HRID 968650ノート

反応式

HRID 968650 の反応式
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](O)=[O:20])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:22][CH2:23][CH:24]1[CH2:29][NH:28][CH2:27][CH2:26][NH:25]1.[ClH:30].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>ClCCl>[ClH:30].[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]([N:28]3[CH2:27][CH2:26][NH:25][CH:24]([CH2:23][F:22])[CH2:29]3)=[O:20])=[CH:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

6

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14479501HCID 14479501、化合物HCID 686950531-(Cyclohexylmethyl)-7-methoxyindole-3-carboxylic acid

生成物 1

HCID 1317267041-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3-(fluoromethyl) piperazine, hydrochloride salt

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1-(cyclohexyl)methyl-7-methoxy-indole-3-carboxylic acid (0.59 g, 2.04 mmol, prepared following the method in Example 1) and 2-(fluoromethyl) piperazine (0.37 g, 3.15 mmol) in dichloromethane (15 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.47 g, 2.45 mmol) and 1-hydroxy benzotriazole (0.07 g, 0.51 mmol). The mixture was stirred at room temperature for 18 h and evaporated. The residue was purified by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane to afford the title compound (free base) as a colourless oil (0.47 g). The free base (0.05 g) was dissolved in diethyl ether (3 ml) and treated dropwise with 2 M hydrochloric acid in diethyl ether (1 ml). The resulting precipitate was collected by filtration, washed with diethyl ether (10 ml) and dried under reduced pressure to afford the title compound (1:1 hydrochloric acid salt) as a colourless solid (0.05 g, 0.12 mmol). 1H NMR (400 MHz, CD3OD) δH 0.98-1.27 (5H, m), 1.57 (2H, br d, J 12.9), 1.63-1.90 (4H, m), 3.21-3.53 (4H, m), 3.68-3.79 (1H, m) 3.95 (3H, s), 4.26 (2H, d, J 7.1), 4.43-4.82 (4H, m), 6.77 (1H, d, J 7.7), 7.11 (1H, t, J 7.5), 7.27 (1H, d, J 8.0), 7.57 (1H, s); EIMS: m/z 270.2 [Fragment+H]+.

後処理

  1. customevaporated
  2. customThe residue was purified by flash chromatography
  3. washeluting with 0-10% (v/v) methanol in dichloromethane

出典と根拠

ORDレコード
ord-950a29b18fe14ea6aed594c5a778537f
出典データセット
uspto-grants-2007_12
特許番号
US07304064B2

反応ノート

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