Sodium hydride → HCID 21717295, compound

HRID 1386355Notes

Reaction equation

HRID 1386355 reaction equation
[CH3:1][NH:2][S:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH2:9]2)(=[O:5])=[O:4].[H-].[Na+].[Cl:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH2:32][CH2:33][CH2:34][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][N:20]=1>CN(C=O)C>[ClH:18].[CH3:30][O:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[O:31][CH2:32][CH2:33][CH2:34][N:35]1[CH2:36][CH2:37][O:38][CH2:39][CH2:40]1)[N:22]=[CH:21][N:20]=[C:19]2[CH:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([S:3]([NH:2][CH3:1])(=[O:5])=[O:4])[CH:7]=2)[NH:11][C:10]1=[O:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10176909N-methyl-2-oxoindoline-5-sulfonamideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717295HCID 21717295, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-methylaminosulphonyloxindole (262 mg, 1.16 mmol) in DMF (3.5 ml) was added dropwise to a suspension of sodium hydride (46 mg, 1.1 6 mmol, prewashed with hexane) in DMF (1.5 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (130 mg, 0.38 mmol), (prepared as described for the starting material in Example 5), was added as a solid. The mixture was stirred for 45 minutes at 60° C. and was then partitioned between ether and water. The aqueous layer was separated and was adjusted to pH7-8 with 1M hydrochloric acid. The precipitate was collected by filtration, washed with water and ether, and dried under vacuum. The solid was suspended in methylene chloride/methanol (1/1) and 2.2M ethereal hydrogen chloride (1.5 ml) was added. The mixture was stirred for 10 minutes at ambient temperature and the volatiles were removed by evaporation. The solid residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 60° C. to give 6-methoxy-4-(5-methylaminosulphonyloxindol-3-yl)-7-(3-morpholinopropoxy)quinazoline hydrochloride (116 mg, 53%).

Workup

  1. additionwas added as a solid
  2. stirringThe mixture was stirred for 45 minutes at 60° C.
  3. customwas then partitioned between ether and water
  4. customThe aqueous layer was separated
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water and ether
  7. customdried under vacuum
  8. addition2.2M ethereal hydrogen chloride (1.5 ml) was added
  9. stirringThe mixture was stirred for 10 minutes at ambient temperature
  10. customthe volatiles were removed by evaporation
  11. customThe solid residue was triturated with ether
  12. filtrationcollected by filtration
  13. washwashed with ether
  14. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-9d96f600e63c4359a811d1f65b922d77
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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