Sodium hydride → 4-(4-Bromo-2-fluorophenylamino)-7-[2-hydroxy-3-(4-pyridylsulphanyl)propoxy]-6-methoxyquinazoline

HRID 1372994Notes

Reaction equation

HRID 1372994 reaction equation
[SH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH:32]4[O:34][CH2:33]4)=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:13]([F:35])[CH:12]=1>CN(C=O)C>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH:32]([OH:34])[CH2:33][S:1][C:2]4[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=4)=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:13]([F:35])[CH:12]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 179746094-(4-Bromo-2-fluorophenylamino)-7-(2,3-epoxypropoxy)-6-methoxyquinazolineHCID 178418431pyridine-4-thiol

Product 1

HCID 179745964-(4-Bromo-2-fluorophenylamino)-7-[2-hydroxy-3-(4-pyridylsulphanyl)propoxy]-6-methoxyquinazolineYield 15.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Mercaptopyridine (93 mg) was added to a suspension of sodium hydride 60% (12 mg) in DMF (2 ml) under nitrogen. After stirring for 15 minutes 4-(4-bromo-2-fluorophenylamino)-7-(2,3-epoxypropoxy)-6-methoxyquinazoline (100 mg) (from Example 5) was added and the mixture was stirred for 3 hours at ambient temperature. The volatiles were removed under vacuum. The residue was partitioned between methylene chloride and water and the pH of the aqueous layer was adjusted to 7 with 1N HCl. The organic layer was separated, washed with water, followed by brine, dried (MgSO4) and evaporated to give 4-(4-bromo-2-fluorophenylamino)-7-[2-hydroxy-3-(4-pyridylsulphanyl)propoxy]-6-methoxyquinazoline (20 mg).

Workup

  1. additionwas added
  2. customThe volatiles were removed under vacuum
  3. customThe residue was partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-afc479c3a03b47a49115137b1235de07
Source dataset
uspto-grants-2007_01
Patent number
US07160889B2

Reaction notes

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