Trifluoroacetic acid → N-(2-Chloro-4-((6-cyano-7-(4-piperidylmethoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea

HRID 853422Notes

Reaction equation

HRID 853422 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:40]=[CH:41][C:42]=1[NH:43][C:44]([NH:46][CH:47]1[CH2:49][CH2:48]1)=[O:45])[O:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH:27]3[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]3)=[C:20]([C:23]#[N:24])[CH:21]=2)[N:16]=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O>[Cl:8][C:9]1[CH:10]=[C:11]([O:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:25][CH2:26][CH:27]4[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]4)=[C:20]([C:23]#[N:24])[CH:21]=3)[N:16]=[CH:15][CH:14]=2)[CH:40]=[CH:41][C:42]=1[NH:43][C:44]([NH:46][CH:47]1[CH2:49][CH2:48]1)=[O:45]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 22936576Tert-butyl 4-(((4-(3-chloro-4-((cyclopropylamino)carbonyl)aminophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

Product 1

HCID 22936852N-(2-Chloro-4-((6-cyano-7-(4-piperidylmethoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylureaYield 99.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

After adding trifluoroacetic acid (2.5 ml) to tert-butyl 4-(((4-(3-chloro-4-((cyclopropylamino)carbonyl)aminophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate (501 mg, 0.846 mmol) at room temperature, the mixture was stirred for 1 hour. The reaction solution was diluted with water (35 ml) while cooling in an ice water bath, and then sodium bicarbonate (3.5 g) was gradually added for neutralization and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was suspended in ethyl acetate and diluted with hexane, and the precipitated crystals were filtered out and blow-dried to obtain the title compound (414.4 mg, 0.842 mmol, 99.6%) as white crystals.

Workup

  1. temperaturewhile cooling in an ice water bath
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. additiondiluted with hexane
  6. filtrationthe precipitated crystals were filtered out and
  7. customblow-dried

Sources & evidence

ORD record
ord-a0119a2b94104726be3a133fa5fa737b
Source dataset
uspto-grants-2007_08
Patent number
US07253286B2

Reaction notes

Loading…