Potassium Carbonate → Quinazoline hydrochloride hydrate

HRID 2182529Notes

Reaction equation

HRID 2182529 reaction equation
[Cl:1]CCCN1CCCC1.[OH:10][C:11]1[CH:20]=[C:19]2[C:14]([CH:15]=[N:16][CH:17]=[N:18]2)=[CH:13][C:12]=1OC.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[OH2:10].[ClH:1].[N:18]1[C:19]2[C:14](=[CH:13][CH:12]=[CH:11][CH:20]=2)[CH:15]=[N:16][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113210281-(3-Chloropropyl)-pyrrolidineHCID 1360078727-Hydroxy-6-methoxyquinazoline

Product 1

HCID 67669263Quinazoline hydrochloride hydrateYield 188.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 1-(3-chloropropyl)pyrrolidine (230 mg, 0.96 mmol) was added to 44-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (295 mg, 0.92 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (130 mg, 0.94 mmol) in DMF (8 ml). The mixture was heated at 100° C. for 90 minutes and allowed to cool. The volatiles were removed by evaporation and the residues were partitioned between water and methylene chloride. The organic phase was separated and passed through phase separating paper, and the solvent was removed under reduced pressure. The residue was dissolved in acetone and hydrogen chloride in ether (2 ml of a 1M solution, 2 mmol) was added. The mixture was stirred at ambient temperature for 30 minutes and the resulting precipitate was collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)6-methoxy-7-(3-pyrrolidin-1-yl)propoxy)quinazoline hydrochloride hydrate (320 mg, 67%).

Workup

  1. custom(prepared
  2. temperatureto cool
  3. customThe volatiles were removed by evaporation
  4. customthe residues were partitioned between water and methylene chloride
  5. customThe organic phase was separated
  6. customseparating paper
  7. customthe solvent was removed under reduced pressure
  8. dissolutionThe residue was dissolved in acetone
  9. additionhydrogen chloride in ether (2 ml of a 1M solution, 2 mmol) was added
  10. filtrationthe resulting precipitate was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-72f8db2d20a647cebff0d5b990b7ee6a
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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