Tetrahydrofuran → HCID 178486369, compound

HRID 1386260Notes

Reaction equation

HRID 1386260 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2.Cl[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](OC)[CH:23]=2)[N:18]=[CH:17][N:16]=1.C1C[O:40][CH2:39]C1>>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH:7]2[C:15]1([O:40][CH3:39])[C:24]2[C:19](=[CH:20][C:21]([O:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[CH:22][CH:23]=2)[N:18]=[CH:17][NH:16]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 178486369HCID 178486369, compound

Procedure

Sodium hydride (80 mg, 3.4 mmol, pre-washed with petroleum ether) was added to a solution of 5-fluorooxindole (423 mg, 2.8 mmol), (prepared according to Synthesis 1993, 51), in THF (10 ml) at ambient temperature under argon. The resulting suspension was stirred for 30 minutes and a partial solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (236 mg, 0.7 mmol), (prepared as described for the starting material in Example 5), in a 1/1 mixture of THFIDMF (14 ml), was added and the reaction mixture was stirred at ambient temperature for 15 hours. The volatiles were then removed by evaporation and the residue purified by column flash chromatography using an increasingly polar mixture of methylene chloride and methanol (2 to 10%) as eluent. The purified product was dissolved in a minimum volume of methanol and a 2.9M solution of hydrogen chloride in ether was added to the solution. During the evaporation of the solvents a solid precipitated which was collected by filtration, washed with ether and dried under vacuum to give 4-(5-fluorooxindol-3-yl)-4-methoxy-7-(3-morpholinopropoxy)quinazoline as a hydrochloride salt (298 mg, 81%).

Workup

  1. additionin a 1/1 mixture of THFIDMF (14 ml)
  2. additionwas added
  3. stirringthe reaction mixture was stirred at ambient temperature for 15 hours
  4. customThe volatiles were then removed by evaporation
  5. customthe residue purified by column flash chromatography
  6. additionan increasingly polar mixture of methylene chloride and methanol (2 to 10%) as eluent
  7. dissolutionThe purified product was dissolved in a minimum volume of methanol
  8. additiona 2.9M solution of hydrogen chloride in ether was added to the solution
  9. customDuring the evaporation of the solvents a solid
  10. customprecipitated which
  11. filtrationwas collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-ea68ae8db955483aa6472f76d045f9f5
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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