Dimethylformamide → HCID 67203053, compound

HRID 388081Notes

Reaction equation

HRID 388081 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([OH:21])=[C:16]([C:19]#[N:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:22][C:23]([NH:25][CH3:26])=[O:24].CN(C)C=O.Br[CH2:33][CH:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[NH:22][C:23]([NH:25][CH3:26])=[O:24])[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:33][CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:44])([CH3:46])[CH3:45])=[O:41])[CH2:36][CH2:35]3)=[C:16]([C:19]#[N:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 135829408N-(2-chloro-4-(6-cyano-7-hydroxyquinolin-4-yloxy)phenyl)-N'-methylurea

Product 1

HCID 67203053HCID 67203053, compoundYield 10.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N-(2-chloro-4-(6-cyano-7-hydroxyquinolin-4-yloxy)phenyl)-N′-methylurea (125 mg) was added to dimethylformamide (1.5 ml), and then tert-butyl 4-(bromomethyl)-1-piperidinecarboxylate (141 mg) and potassium carbonate (93 mg) were added thereto and the mixture was heated at 60° C. for 3 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate, the organic layer was washed with water and saturated saline in that order and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was recrystallized with ethyl acetate to obtain tert-butyl 4-(((4-(3-chloro-4-((methylamino)carbonyl)aminophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate (21 mg) as light yellow crystals. These were dissolved in trifluoroacetic acid (1.0 ml), and the solution was stirred for 10 minutes at room temperature. Water (2 ml) was added, the mixture was neutralized with sodium bicarbonate, and the precipitated crystals were filtered out to obtain the title compound (16 mg).

Workup

  1. washthe organic layer was washed with water and saturated saline in that order
  2. dry with materialdried over anhydrous sodium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe obtained crude product
  5. customwas recrystallized with ethyl acetate

Sources & evidence

ORD record
ord-6f3f9037223544b296d6cad8cbc21e64
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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