Dimethylformamide → HCID 21717248, compound

HRID 1386273Notes

Reaction equation

HRID 1386273 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][N:16]=1.CN(C=O)C>C1COCC1>[ClH:14].[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:27][CH2:28][CH2:29][CH2:30][N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)=[C:22]([O:25][CH3:26])[CH:23]=4)[N:18]=[CH:17][N:16]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 37310136-fluoro-2,3-dihydro-1H-indol-2-oneHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717248HCID 21717248, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-fluorooxindole (227 mg, 1.5 mmol), (prepared according to Synthesis 1993, 51), in THF (3 ml) was added dropwise under nitrogen to sodium hydride (42 mg, 1.75 mmol, pre-washed with hexane). After stirring the resulting mixture for 20 minutes at ambient temperature, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (169 mg, 0.5 mmol), (prepared as described for the starting material in Example 5), was added as a solid, followed by DMF (3 ml). The mixture was then heated at 75° C. for 1 hour, allowed to cool and the solvent removed by evaporation The mixture was partitioned between water and ether. The aqueous layer was separated and adjusted to pH8 with 2M hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with brine, dried and volatiles removed by evaporation. The residue was triturated with ether and collected by filtration. This solid was dissolved in methylene chloride/methanol, a 5M solution of hydrogen chloride in isopropanol (0.5 ml) was added and the volatiles removed by evaporation. The resulting solid was collected by filtration, washed with ether and dried under vacuum to give 4-(6-fluorooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (198 mg, 81%) as a yellow solid.

Workup

  1. additionwas added as a solid
  2. temperatureThe mixture was then heated at 75° C. for 1 hour
  3. temperatureto cool
  4. customthe solvent removed by evaporation The mixture
  5. customwas partitioned between water and ether
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with brine
  9. customdried
  10. customvolatiles removed by evaporation
  11. customThe residue was triturated with ether
  12. filtrationcollected by filtration
  13. dissolutionThis solid was dissolved in methylene chloride/methanol
  14. additiona 5M solution of hydrogen chloride in isopropanol (0.5 ml) was added
  15. customthe volatiles removed by evaporation
  16. filtrationThe resulting solid was collected by filtration
  17. washwashed with ether
  18. customdried under vacuum

Sources & evidence

ORD record
ord-b20ce5ebb40349b68b02b6786302108f
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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