Hydrochloric Acid → HCID 21717170, compound

HRID 1386324Notes

Reaction equation

HRID 1386324 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][N:31]3[CH:35]=[CH:34][N:33]=[CH:32]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1.[Cl-].[NH4+].Cl>CN(C=O)C.C(Cl)Cl.CO>[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][N:31]3[CH:35]=[CH:34][N:33]=[CH:32]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1)#[N:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 111412614-Chloro-6-methoxy-7-(2-(imidazol-1-yl)ethoxy)quinazoline

Product 1

HCID 21717170HCID 21717170, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 5-cyanooxindole (2.96 g, 18.7 mmol), (Tet. Lett., 1987, 28, 4027), in DMF (35 ml) was added dropwise under nitrogen to sodium hydride (749 mg, 18.7 mmol, prewashed with hexane) in DMF (15 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (1.98 g, 18.7 mmol), (prepared as described for the starting material in Example 22), was added as a solid. The mixture was heated at 55° C. for 45 minutes, allowed to cool and poured into a mixture of methylene chloride (400 ml) and saturated aqueous ammonium chloride solution (400 ml). The resulting precipitate was collected by filtration, resuspended in water and stirred for 15 minutes at ambient temperature. The solid was collected by filtration, washed with water and then ether, and dried under vacuum to give a white solid. This solid was suspended in methylene chloride (50 ml) and methanol (50 ml) and 2.2M ethereal hydrogen chloride (6 ml) was added. The mixture was stirred for 15 minutes at ambient temperature, the solid product was collected by filtration, washed with ether and dried under vacuum at 60° C. to give 4-(5-cyanooxindol-3-yl)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline hydrochloride (2 g, 61%).

Workup

  1. additionwas added as a solid
  2. temperatureThe mixture was heated at 55° C. for 45 minutes
  3. temperatureto cool
  4. filtrationThe resulting precipitate was collected by filtration
  5. stirringstirred for 15 minutes at ambient temperature
  6. filtrationThe solid was collected by filtration
  7. washwashed with water
  8. dry with materialether, and dried under vacuum
  9. customto give a white solid
  10. stirringThe mixture was stirred for 15 minutes at ambient temperature
  11. filtrationthe solid product was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-e8e190ad8e8c4a9cac803c059bc614be
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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