Hydrochloric Acid → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline hydrochloride

HRID 1384569Notes

Reaction equation

HRID 1384569 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:30]=[C:29]([CH3:31])[C:28]([O:32]C(OC)=O)=[CH:27][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[CH:23]3)=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[CH:9][N:8]=1.O.[ClH:38]>CO>[ClH:38].[F:3][C:4]1[CH:30]=[C:29]([CH3:31])[C:28]([OH:32])=[CH:27][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[CH:23]3)=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[CH:9][N:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 226250254-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline

Product 1

HCID 226250234-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline hydrochlorideYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

2M Aqueous sodium hydroxide (0.3 ml, 6 mmol) was added to a solution of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (257 mg, 5.5 mmol) in methanol (5 ml) and the mixture stirred for 1 hour at 40° C. Water and 1M hydrochloric acid (0.6 ml) were added and the mixture concentrated to half volume by evaporation. The resulting solid was collected by filtration, dissolved in methylene chloride/methanol and a solution of 7M hydrogen chloride in isopropanol (0.4 ml) was added. The volatiles were removed by evaporation, the solid residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline hydrochloride (160 mg, 60%). m.p. 195-220° C. 1H NMR Spectrum: (DMSOd6) 2.16(s, 3H); 4.0(s, 3H); 4.63(t, 2H); 4.76(t, 2H); 6.90(d, 1H); 7.1(d, 1H); 7.44(s, 1H); 7.72(s, 1H); 7.83(s, 1H); 8.31(s, 1H); 8.76(s, 1H); 9.20(s, 1H); 9.7(s, 1H); 11.4(br s, 1H) MS-ESI: 410 [MH]+

Workup

  1. concentrationthe mixture concentrated to half volume by evaporation
  2. filtrationThe resulting solid was collected by filtration
  3. dissolutiondissolved in methylene chloride/methanol
  4. additiona solution of 7M hydrogen chloride in isopropanol (0.4 ml) was added
  5. customThe volatiles were removed by evaporation
  6. customthe solid residue was triturated with ether
  7. filtrationcollected by filtration
  8. customdried under vacuum

Sources & evidence

ORD record
ord-7a86daf0282449668344c69ee032218e
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

Loading…