Ammonia → 2-Methyl-4-[(5-fluoroquinazolin-4-yl)amino]phenol

HRID 1864191Notes

Reaction equation

HRID 1864191 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([CH3:21])[CH:15]=1.N>C(O)(C)C>[CH3:21][C:16]1[CH:15]=[C:14]([NH:13][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][C:10]=3[F:12])[N:5]=[CH:4][N:3]=2)[CH:19]=[CH:18][C:17]=1[OH:20]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 760815-Amino-2-hydroxytolueneHCID 119744454-Chloro-5-fluoroquinazoline

Product 1

HCID 574449792-Methyl-4-[(5-fluoroquinazolin-4-yl)amino]phenolYield 82%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

4-Chloro-5-fluoroquinazoline (6.76 g) was dissolved in iso-propanol (200 ml) and 4-amino-2-methylphenol (5.00 g) was added. The mixture was heated under reflux for 2 hours, causing a yellow solid to precipitate. The mixture was cooled to ambient temperature and the solid was collected by filtration. The solid was dissolved in a boiling mixture of methanol (500 ml) and water (100 ml) to give a brown solution. With vigorous stirring, the solution was basified with aqueous ammonia (0.880, 10 ml), causing a light brown solid to precipitate. The mixture was concentrated in vacuo to such a volume that all of the methanol had been removed, leaving the product as a suspension in aqueous solution. The suspension was cooled; the solid was collected by filtration, triturated with ethyl acetate and dried over P2O5 in a vacuum oven to give 2-methyl-4-[(5-fluoroquinazolin-4-yl)amino]phenol as a light brown solid (8.18 g, 82%); NMR spectrum (DMSO-d6) 3.30 (s, 3H), 6.78 (d, 1H), 7.28 (m, 2H), 7.38 (dd, 1H), 7.57 (d, 1H), 7.78 (m, 1H), 8.43 (s, 1H), 8.88 (d, 1H), 9.22 (s, 1H); Mass spectrum MH+ 270.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customto precipitate
  4. filtrationthe solid was collected by filtration
  5. dissolutionThe solid was dissolved in a boiling mixture of methanol (500 ml) and water (100 ml)
  6. customto give a brown solution
  7. customto precipitate
  8. concentrationThe mixture was concentrated in vacuo to such a volume that all of the methanol
  9. customhad been removed
  10. customleaving the product as a suspension in aqueous solution
  11. temperatureThe suspension was cooled
  12. filtrationthe solid was collected by filtration
  13. customtriturated with ethyl acetate
  14. dry with materialdried over P2O5 in a vacuum oven

Sources & evidence

ORD record
ord-160d2c4eb604417fa8fcee0eab721552
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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