Potassium Carbonate → N-(4-(6-Cyano-7-(3-(morpholin-4-yl)propoxy)-4-quinolyl)oxyphenyl)-N'-(4-methoxyphenyl)urea

HRID 1010087Notes

Reaction equation

HRID 1010087 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O-:13])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[O:23])=[CH:17][CH:16]=1)#[N:2].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:41][CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>CN(C)C=O.[Cl-].[Na+].O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:41][CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1)[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[O:23])=[CH:17][CH:16]=1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 958344-(3-Chloropropyl)morpholineHCID 23711333Sodium 6-cyano-4-(4-((4-methoxyanilino)carbonyl)aminophenoxy)-7-quinolinolate

Product 1

HCID 10120172N-(4-(6-Cyano-7-(3-(morpholin-4-yl)propoxy)-4-quinolyl)oxyphenyl)-N'-(4-methoxyphenyl)ureaYield 97.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

The sodium 6-cyano-4-(4-((4-methoxyanilino)carbonyl)aminophenoxy)-7-quinolinolate (100 mg) synthesized in Example 87 was dissolved in dimethylformamide (2.5 ml), and then potassium carbonate (65 mg, 0.4690 mmol) and 1-chloro-3-(morpholin-4-yl)propane (38 mg, 0.2345 mmol, J. Am. Chem. Soc. 67, 736 (1945)) were added and the mixture was heated and stirred at 80° C. for 2 hours. After allowing the mixture to stand and adding saturated brine, it was extracted with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system). The obtained crystals were suspended in ethyl acetate, the suspension was diluted with diethyl ether, and the crystals were filtered out, washed with diethyl ether and dried by aspiration to obtain the title compound (120 mg) as light yellow crystals.

Workup

  1. temperaturethe mixture was heated
  2. extractionwas extracted with ethyl acetate
  3. washthe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customthe residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system)
  7. additionthe suspension was diluted with diethyl ether
  8. filtrationthe crystals were filtered out
  9. washwashed with diethyl ether
  10. customdried by aspiration

Sources & evidence

ORD record
ord-48ef24ee872b4e4380cfd9a843783bf6
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

Loading…