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

HRID 1433467Notes

Reaction equation

HRID 1433467 reaction equation
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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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 brine, 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 180 mg of the target substance.

Workup

  1. stirringthe mixture was further stirred for 30 minutes
  2. extractionextraction
  3. washThe organic layer was washed twice with water and once with brine
  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

Sources & evidence

ORD record
ord-d3169d8c5700498d989a24ea1ed69ca1
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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