Potassium Carbonate → HCID 19077516, compound

HRID 964538Notes

Reaction equation

HRID 964538 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([OH:16])[CH:14]=2)[N:9]=[CH:8][N:7]=1.Cl.[N:24]1([CH2:29][CH2:30][CH2:31]Cl)[CH2:28][CH2:27][CH2:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([O:16][CH2:31][CH2:30][CH2:29][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 115719161-(3-chloropropyl)pyrrolidine Hydrochloride

Product 1

HCID 19077516HCID 19077516, compoundYield 5.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(3'-chloro-4'-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (1.28 g), 3-(pyrrolidin-1-yl)propyl chloride hydrochloride (Chem. Abs., 82, 57736; 1.5 g), potassium carbonate (2.8 g) and DMF (20 ml) was stirred and heated to 80° C. for 5 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic phase was washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 20:3 mixture of methylene chloride and methanol as eluent. The material so obtained (1.1 g) was triturated under ethyl acetate to give 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-pyrrolidin-1-ylpropoxy)quinazoline (0.094 g). The organic solution was evaporated and the residual solid was recrystallised from acetonitrile. There was thus obtained a second crop (0.85 g) of the same product. The material gave the following characterising data:

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with water
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. additiona 20:3 mixture of methylene chloride and methanol as eluent
  8. customThe material so obtained (1.1 g)
  9. customwas triturated under ethyl acetate

Sources & evidence

ORD record
ord-2b4179196a21498593d2baa7b93de229
Source dataset
uspto-grants-1998_06
Patent number
US05770599

Reaction notes

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