Hydrochloric Acid → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholinopropionamido)quinazoline

HRID 634732Notes

Reaction equation

HRID 634732 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:31]=[C:30]([CH3:32])[C:29]([O:33]C(OC)=O)=[CH:28][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18](=[O:27])[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1.Cl>CO.O>[F:3][C:4]1[CH:31]=[C:30]([CH3:32])[C:29]([OH:33])=[CH:28][C:5]=1[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18](=[O:27])[CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 212603554-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(3-morpholinopropionamido)quinazoline

Product 1

HCID 212603194-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholinopropionamido)quinazolineYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

2M Aqueous sodium hydroxide solution (453 μl, 0.9 mmol) was added to a suspension of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-(3-morpholinopropionamido)quinazoline (219 mg, 0.45 mmol) in methanol (6 ml) and the mixture stirred for 1 hour. The reaction mixture was diluted with water and then adjusted to pH6 with 2M hydrochloric acid. The resulting precipitate was collected by filtration, washed with water and ethanol, and dried. The solid was dissolved in methylene chloride/methanol and a 5M solution of hydrogen chloride in isopropanol (0.3 ml) added. The volatiles were removed by evaporation, the resulting solid was washed with ether, and dried under vacuum to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholinopropionamido)quinazoline (1-86 mg, 80%) as a yellow solid.

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with water and ethanol
  3. customdried
  4. dissolutionThe solid was dissolved in methylene chloride/methanol
  5. additiona 5M solution of hydrogen chloride in isopropanol (0.3 ml) added
  6. customThe volatiles were removed by evaporation
  7. washthe resulting solid was washed with ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-acf00f39016b4701a3e228fcd490f95f
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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