Hydrochloric Acid → HCID 21717183, compound

HRID 1386304Notes

Reaction equation

HRID 1386304 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2)#[N:2].[H-].[Na+].[Cl:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1.Cl>CN(C=O)C.O>[ClH:15].[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]2[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1)#[N:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717183HCID 21717183, compoundYield 53.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-cyanooxindole (213 mg, 1.35 mmol), (Tet. Lett., 1987, 28, 4027), in DMF (3 ml) was added dropwise to a suspension of sodium hydride (54 mg, 1.35 mmol, prewashed with hexane) in DMF (2 ml). The mixture was stirred for 20 minutes at ambient temperature, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (152 mg, 0.45 mmol), (prepared as described for the starting material in Example 5), was added and the mixture was heated at 70° C. for 1 hour. The mixture was allowed to cool and then was diluted with water and adjusted to pH1 with 2M hydrochloric acid. The solution was washed with ether and then basified with aqueous sodium hydrogen carbonate solution. The resulting precipitate was collected by filtration, washed with water, ether and dried under vacuum. The solid was purified by flash chromatography eluting with methylene chloride/methanol (90/10 followed by 80/20). The purified solid was dissolved in methylene chloride/methanol and 5M methanolic hydrogen chloride (0.5 ml) was added. The solution was concentrated by evaporation to a total volume of 2 ml and ether (15 ml) was added. The resulting solid was collected by filtration, washed with ether and dried under vacuum to give 4-(5-cyanooxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (120 mg, 50%).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 70° C. for 1 hour
  3. temperatureto cool
  4. washThe solution was washed with ether
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed with water, ether
  7. customdried under vacuum
  8. customThe solid was purified by flash chromatography
  9. washeluting with methylene chloride/methanol (90/10 followed by 80/20)
  10. dissolutionThe purified solid was dissolved in methylene chloride/methanol
  11. addition5M methanolic hydrogen chloride (0.5 ml) was added
  12. concentrationThe solution was concentrated by evaporation to a total volume of 2 ml and ether (15 ml)
  13. additionwas added
  14. filtrationThe resulting solid was collected by filtration
  15. washwashed with ether
  16. customdried under vacuum

Sources & evidence

ORD record
ord-c7a024988d0541cb8951ac1a360548e4
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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