5-Amino-4-fluoro-2-methylphenol → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(4-pyridylmethoxy)quinazoline hydrochloride

HRID 1384557Notes

Reaction equation

HRID 1384557 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[F:21][C:22]1[CH:28]=[C:27]([CH3:29])[C:26]([OH:30])=[CH:25][C:23]=1[NH2:24]>C(O)(C)C>[ClH:2].[F:21][C:22]1[CH:28]=[C:27]([CH3:29])[C:26]([OH:30])=[CH:25][C:23]=1[NH:24][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1

Participants

4

Reactant 2

HCID 101540985-Amino-4-fluoro-2-methylphenolHCID 226250794-Chloro-7-(4-pyridylmethoxy)quinazoline hydrochloride

Product 1

HCID 226250164-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(4-pyridylmethoxy)quinazoline hydrochlorideYield 33.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 4-chloro-7-(4-pyridylmethoxy)quinazoline hydrochloride (350 mg, 1 mmol) and 2-fluoro-5-hydroxy-4-methylaniline (155 mg, 1.1 mmol), (prepared as described for the starting material in Example 13), in isopropanol (15 ml) was heated at reflux for 1 hour. The resulting precipitate was collected by filtration and purified by reverse phase HPLC using a gradient (0-75%) of methanol in water. Concentrated hydrochloric acid (0.5 ml) was added to the combined fractions of pure product and the solvent was removed by evaporation to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(4-pyridylmethoxy)quinazoline hydrochloride (140 mg, 28%). 1H NMR Spectrum: (DMSOd6) 2.16(s, 3H); 5.69(s, 2H); 6.19(d, 1H); 7.1 (d, 1H); 7.48(d, 1H); 7.66(dd, 1H); 8.06(d, 2H); 8.84(s, 1H); 8.86(d, 1H); 8.90(d, 2H); 9.7(br s, 1H); 11.71(s, 1H) MS-ESI: 377 [MH]+

Workup

  1. custom(prepared
  2. temperaturewas heated
  3. temperatureat reflux for 1 hour
  4. filtrationThe resulting precipitate was collected by filtration
  5. custompurified by reverse phase HPLC
  6. additionConcentrated hydrochloric acid (0.5 ml) was added to the combined fractions of pure product
  7. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-35239442e8244058bd64179f921a6181
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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