Potassium Carbonate → HCID 18474783, compound

HRID 547169Notes

Reaction equation

HRID 547169 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[OH2:26].[ClH:1].[Cl:10][C:11]1[CH:30]=[CH:29][C:14]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:2][CH2:3][CH2:4][N:5]4[CH2:9][CH2:8][CH2:7][CH2:6]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:13]([F:31])[CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113210281-(3-Chloropropyl)-pyrrolidineHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18474783HCID 18474783, compoundYield 143.3%

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 4-(4-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-0a64ff265215482d89e0e4456ab723b9
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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