Hydrochloric Acid → 4-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride

HRID 279553Notes

Reaction equation

HRID 279553 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[C:32]([O:33]C(OC)=O)=[CH:31][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1.O.Cl>CO>[ClH:3].[Cl:3][C:4]1[C:32]([OH:33])=[CH:31][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 22624977HCID 22624977, compound

Product 1

HCID 226248824-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochlorideYield 150.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2M Aqueous sodium hydroxide (1.5 ml, 3 mmol) was added to a solution of 4-(4-chloro-2-fluoro-5-methoxycarbonyloxyanilino)-6-methoxy-7-(3 -(4-pyridyl)propoxy)quinazoline (1.28 g, 2.5 mmol) in methanol (13 ml) and the mixture stirred for 2 hours at ambient temperature. Water was added and the mixture was adjusted to pH7 with 2M hydrochloric acid. The resulting precipitate was collected by filtration, washed with water and dried under vacuum. This solid was dissolved in methylene chloride (30 ml) and methanol (5 ml) and a solution of 5M hydrogen chloride in isopropanol (2.5 ml) was added. The solution was diluted with isopropanol and concentrated under vacuum to a total volume of 10 ml. The resulting solid was collected by filtration, washed with isopropanol and then ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride (924 mg, 70%).

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with water
  3. customdried under vacuum
  4. dissolutionThis solid was dissolved in methylene chloride (30 ml)
  5. additionmethanol (5 ml) and a solution of 5M hydrogen chloride in isopropanol (2.5 ml) was added
  6. additionThe solution was diluted with isopropanol
  7. concentrationconcentrated under vacuum to a total volume of 10 ml
  8. filtrationThe resulting solid was collected by filtration
  9. washwashed with isopropanol
  10. dry with materialether and dried under vacuum

Sources & evidence

ORD record
ord-ec4e1eef10fb4a0eb22eee102703ba90
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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