Methanesulfonic Acid → N-(2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea

HRID 1008342Notes

Reaction equation

HRID 1008342 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][CH2:30][CH2:31][CH3:32])=[O:28])=[C:22]([Cl:33])[CH:21]=3)=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:34][CH3:35])C1C=CC=CC=1.CS(O)(=O)=O>FC(F)(F)C(O)=O>[Cl:33][C:22]1[CH:21]=[C:20]([O:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:34][CH3:35])[CH:11]=3)[N:16]=[CH:15][N:14]=2)[CH:25]=[CH:24][C:23]=1[NH:26][C:27]([NH:29][CH2:30][CH2:31][CH3:32])=[O:28]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 22667035N-(4-{[7-(Benzyloxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl)-N'-propylurea

Product 1

HCID 135674214N-(2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N'-propylureaYield 60%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
100 °C

Procedure

N-(4-{[7-(Benzyloxy)-6-methoxy-4-quinazolinyl]oxy}-2-chlorophenyl)-N′-propylurea (42.2 g) was dissolved in trifluoroacetic acid (200 ml). Methanesulfonic acid (11.1 ml) was then added to the solution, and the mixture was stirred at 100° C. for 4 hr. The reaction solution was cooled to room temperature, and trifluoroacetic acid was removed by distillation under the reduced pressure. Chloroform and methanol were added to the mixture as the residue, followed by extraction with a 10% aqueous sodium hydroxide solution three times. The aqueous layer was neutralized with concentrated hydrochloric acid to precipitate a solid. The solid was washed with water, methanol, and ether in that order, and was then dried in vacuo through a vacuum pump to give 20.7 g (yield 60%) of the title compound.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. customtrifluoroacetic acid was removed by distillation under the reduced pressure
  3. additionChloroform and methanol were added to the mixture as the residue
  4. extractionfollowed by extraction with a 10% aqueous sodium hydroxide solution three times
  5. customto precipitate a solid
  6. washThe solid was washed with water, methanol, and ether in that order
  7. customwas then dried in vacuo through a vacuum pump

Sources & evidence

ORD record
ord-6db825b9e901445181630c0138eb4028
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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