N-methyl-2-pyrrolidone → N-(4-(6-Cyano-7-benzyloxy-4-quinolyl)oxyphenyl)-N'-(4-methoxyphenyl)urea

HRID 1433370Notes

Reaction equation

HRID 1433370 reaction equation
CN1CCCC1=O.C(N(C(C)C)CC)(C)C.[OH:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)=[O:26])=[CH:20][CH:19]=1.Cl[C:37]1[C:46]2[C:41](=[CH:42][C:43]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[C:44]([C:47]#[N:48])[CH:45]=2)[N:40]=[CH:39][CH:38]=1>C(OCC)(=O)C.O1CCCC1>[C:47]([C:44]1[CH:45]=[C:46]2[C:41](=[CH:42][C:43]=1[O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[N:40]=[CH:39][CH:38]=[C:37]2[O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)=[O:26])=[CH:20][CH:19]=1)#[N:48]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531Diisopropylethylamine2×HCID 14545055N-(4-hydroxyphenyl)-N'-(4-methoxyphenyl)ureaHCID 226465197-Benzyloxy-4-chloro-6-cyanoquinoline

Product 1

HCID 22936656N-(4-(6-Cyano-7-benzyloxy-4-quinolyl)oxyphenyl)-N'-(4-methoxyphenyl)ureaYield 43.52%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

After adding 1-methylpyrrolidone (3.4 ml) and diisopropylethylamine (3.6 ml, 20.78 mmol) to N-(4-hydroxyphenyl)-N′-(4-methoxyphenyl)urea (4.25 g, 16.46 mmol), the mixture was heated and stirred at 130° C. to complete dissolution, and then 4-chloro-6-cyano-7-benzyloxyquinoline (5.10 g, 17.32 mmol) was added and the mixture was stirred at 130° C. for 1.5 hours and at 150° C. for 1 hour. Upon addition of diisopropylethylamine (1.2 ml, 6.93 mmol), the mixture was further stirred for 1 hour. After cooling and adding tetrahydrofuran and ethyl acetate, the mixture was washed with saturated sodium bicarnobate water and saturated brine and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtain crystals were washed with diethyl ether/hexane, acetonitrile/diethyl ether/hexane, methanol and dimethylsulfoxide/water, in that order. The obtained crystals were dissolved in tetrahydrofuran, filtered with silica gel (200 cc silica gel) and flushed with 3000 ml of tetrahydrofuran, and the solvent was distilled off under reduced pressure. The crystals were then washed with diethyl ether, acetonitrile and diethyl ether:ethanol=5:1 and dried by aspiration to obtain the title compound (3.70 g, 7.1627 mmol, 43.52%) as brown crystals.

Workup

  1. temperaturethe mixture was heated
  2. dissolutiondissolution
  3. stirringthe mixture was stirred at 130° C. for 1.5 hours and at 150° C. for 1 hour
  4. stirringthe mixture was further stirred for 1 hour
  5. temperatureAfter cooling
  6. washthe mixture was washed with saturated sodium bicarnobate water and saturated brine
  7. dry with materialdried over magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. washThe obtain crystals were washed with diethyl ether/hexane, acetonitrile/diethyl ether/hexane, methanol and dimethylsulfoxide/water, in that order
  10. dissolutionThe obtained crystals were dissolved in tetrahydrofuran
  11. filtrationfiltered with silica gel (200 cc silica gel)
  12. customflushed with 3000 ml of tetrahydrofuran
  13. distillationthe solvent was distilled off under reduced pressure
  14. washThe crystals were then washed with diethyl ether, acetonitrile and diethyl ether
  15. dry with materialethanol=5:1 and dried by aspiration

Sources & evidence

ORD record
ord-2f4ce01e610f48118096dddcba6da754
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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