Sodium hydride → 6-Methoxy-7-(2-methoxyethoxy)-4-(5-(2-morpholinoacetyl)oxindol-3-yl)quinazoline hydrochloride

HRID 1386313Notes

Reaction equation

HRID 1386313 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16](=[O:21])[CH2:15]3)=[O:11])[CH2:5][CH2:4]1.[Cl:22][C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:35][CH2:36][CH2:37][O:38][CH3:39])=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][N:24]=1>CN(C=O)C>[ClH:22].[CH3:34][O:33][C:30]1[CH:31]=[C:32]2[C:27](=[CH:28][C:29]=1[O:35][CH2:36][CH2:37][O:38][CH3:39])[N:26]=[CH:25][N:24]=[C:23]2[CH:15]1[C:14]2[C:18](=[CH:19][CH:20]=[C:12]([C:10](=[O:11])[CH2:9][N:6]3[CH2:7][CH2:8][O:3][CH2:4][CH2:5]3)[CH:13]=2)[NH:17][C:16]1=[O:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazolineHCID 21717309HCID 21717309, compound

Product 1

HCID 217172846-Methoxy-7-(2-methoxyethoxy)-4-(5-(2-morpholinoacetyl)oxindol-3-yl)quinazoline hydrochlorideYield 42.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (58 mg, 2.4 mmol) was added to solution of 5-(2-morpholinoacetyl)oxindole (312 mg, 1.2 mmol) and 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (160 mg, 0.6 mmol), (prepared as described for the starting material in Example 2), in DMF (15 ml). The mixture was stirred for 1.5 hours at ambient temperature and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (96/4 followed by 94/6). The purified solid product was triturated with ether, collected by filtration, washed with ether and dried under vacuum. The solid was dissolved in methylene chloride (10 ml) and methanol (10 ml) and 1M methanolic hydrogen chloride (2 ml) was added. The volatiles were removed by evaporation and the solid residue was suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-7-(2-methoxyethoxy)-4-(5-(2-morpholinoacetyl)oxindol-3-yl)quinazoline hydrochloride (136 mg, 39%).

Workup

  1. custom(prepared
  2. customthe volatiles were removed by evaporation
  3. customThe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (96/4 followed by 94/6)
  5. customThe purified solid product was triturated with ether
  6. filtrationcollected by filtration
  7. washwashed with ether
  8. customdried under vacuum
  9. dissolutionThe solid was dissolved in methylene chloride (10 ml)
  10. additionmethanol (10 ml) and 1M methanolic hydrogen chloride (2 ml) was added
  11. customThe volatiles were removed by evaporation
  12. filtrationcollected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-1235ee365948454aa6b0b0f91fd14dea
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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