Pyridine → tert-Butyl 4-(((6-cyano-4-(3-fluoro-4-((phenoxycarbonyl)amino)phenoxy)-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

HRID 1433707Notes

Reaction equation

HRID 1433707 reaction equation
[NH2:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[F:36].N1C=CC=CC=1.Cl[C:44]([O:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:45]>O1CCCC1>[C:17]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH2:20][CH:21]1[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:25][CH2:26]1)[N:10]=[CH:9][CH:8]=[C:7]2[O:6][C:5]1[CH:34]=[CH:35][C:2]([NH:1][C:44]([O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:45])=[C:3]([F:36])[CH:4]=1)#[N:18]

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 22936777tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

Product 1

HCID 22936279tert-Butyl 4-(((6-cyano-4-(3-fluoro-4-((phenoxycarbonyl)amino)phenoxy)-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate (523 mg), pyridine (0.17 ml) and tetrahydrofuran (10 ml) were stirred while cooling on ice, and then phenyl chloroformate was added dropwise. Immediately after completion of the dropwise addition, the cooling bath was removed and the mixture was returned to room temperature. After 15 minutes of stirring, water and ethyl acetate were added for extraction. Silica gel was added to the extract and the solvent was distilled off under reduced pressure for adsorption. The reaction solution-adsorbed silica gel was purified by column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, ethyl acetate) in a dry column packed with silica gel, to obtain 490 mg of a yellow powder.

Workup

  1. temperaturewhile cooling on ice
  2. additionImmediately after completion of the dropwise addition
  3. customthe cooling bath was removed
  4. customwas returned to room temperature
  5. additionwater and ethyl acetate were added for extraction
  6. additionSilica gel was added to the
  7. extractionextract
  8. distillationthe solvent was distilled off under reduced pressure for adsorption
  9. customThe reaction solution-adsorbed silica gel
  10. customwas purified by column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, ethyl acetate) in a dry column

Sources & evidence

ORD record
ord-4a4db483e528416e94c6d3e751a34537
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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