Pyridine → Tert-butyl 4-{2-[(4-{3-chloro-4-[(phenoxycarbonyl)amino]phenoxy}-2-pyridyl)amino]-2-oxoethyl}-1-piperidinecarboxylate

HRID 387815ノート

反応式

HRID 387815 の反応式
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[NH2:11][C:12]1[CH:41]=[CH:40][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:39])[CH2:25][CH:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)[CH:18]=2)=[CH:14][C:13]=1[Cl:42].N1C=CC=CC=1.CN(C)C=O>O>[Cl:42][C:13]1[CH:14]=[C:15]([CH:40]=[CH:41][C:12]=1[NH:11][C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3])[O:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:39])[CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:33])[CH2:28][CH2:27]2)[CH:18]=1

参加物

6

反応物 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 15891Phenyl chloroformateHCID 22936879tert-Butyl4-(2-{[4-(4-amino-3-chlorophenoxy)-2-pyridyl]amino}-2-oxoethyl)-1-piperidinecarboxylate

生成物 1

HCID 67202218Tert-butyl 4-{2-[(4-{3-chloro-4-[(phenoxycarbonyl)amino]phenoxy}-2-pyridyl)amino]-2-oxoethyl}-1-piperidinecarboxylate収率 61.2%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Phenyl chloroformate (210 mg) was added dropwise to a solution of 570 mg of tert-butyl 4-(2-{[4-(4-amino-3-chlorophenoxy)-2-pyridyl]amino}-2-oxoethyl)-1-piperidinecarboxylate, 110 mg of pyridine and 5 ml of dimethylformamide while stirring at room temperature, and the mixture was further stirred for 30 minutes. Water was added and extraction was performed with ethyl acetate. The organic layer was washed twice with water and once with saline, and then silica gel was added and the solvent was distilled off under reduced pressure. This was then charged into a dry column packed with silica gel and purification was performed by column chromatography (hexane:ethyl acetate=1:1, followed by ethyl acetate), to obtain 440 mg of tert-butyl 4-{2-[(4-{3-chloro-4-[(phenoxycarbonyl)amino]phenoxy}-2-pyridyl)amino]-2-oxoethyl}-1-piperidinecarboxylate as a light yellow oil. After adding 71 mg of aniline and 5 ml of dimethylformamide to the oil, it was stirred at 130° C. for 15 minutes. The reaction solution was returned to room temperature, NH type silica gel was added, the solvent was distilled off under reduced pressure and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and column purification was performed (hexane:ethyl acetate=1:1). The solvent was distilled off under reduced pressure to obtain 80 mg of the target substance.

後処理

  1. stirringthe mixture was further stirred for 30 minutes
  2. extractionextraction
  3. washThe organic layer was washed twice with water and once with saline
  4. additionsilica gel was added
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionThis was then charged into a dry column
  7. custompacked with silica gel and purification

出典と根拠

ORDレコード
ord-d34fbbb6a7dd46e5a64213d582607aad
出典データセット
uspto-grants-2013_02
特許番号
US08372981B2

反応ノート

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