Sodium hydride → HCID 10299605, compound

HRID 445167Notes

Reaction equation

HRID 445167 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[CH2:5][N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:16][CH2:17][C:18]#[CH:19])=[CH:13][CH:14]=2)[C:9]([C:20]2[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=2)=[N:8][C:7]1=[O:29].[H-].[Na+].Br[CH2:36][CH2:37][O:38][CH3:39]>CN(C=O)C>[CH:26]([C:23]1[CH:24]=[CH:25][C:20]([C:9]2[C:10]3[C:15](=[CH:14][CH:13]=[C:12]([O:16][CH2:17][C:18]#[CH:19])[CH:11]=3)[N:6]([CH2:5][C:4]3[CH:30]=[CH:31][CH:32]=[C:2]([O:1][CH2:36][CH2:37][O:38][CH3:39])[CH:3]=3)[C:7](=[O:29])[N:8]=2)=[CH:21][CH:22]=1)([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 10273916HCID 10273916, compound

Product 1

HCID 10299605HCID 10299605, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 100 mg (0.236 mmol) of 1-(3-hydroxy-benzyl)-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one in anhydrous DMF (5 ml) is added NaH (11 mg, 0.471 mmol) and the solution is allowed to stir until evolution of gas ceases. 1-Bromo-2-methoxy-ethane (34 μl, 0.236 mmol) is added and the mixture is heated for 2 days at 60° C. After cooling to room temperature, the reaction mixture is quenched with water and the mixture is acidified to pH 3 with 10% citric acid. The mixture is extracted with ether (2×20 ml). The combined organic layers are washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to provide a yellow solid which is purified by flash chromatography on silica gel using petroleum ether/ethyl acetate (9:1 to 1:1) to provide the title compound as a yellow oil. Yield:56 mg (49%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture is quenched with water
  3. extractionThe mixture is extracted with ether (2×20 ml)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto provide a yellow solid which
  9. customis purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-c5010215b1b64842ad8d1128f7cb1a1e
Source dataset
uspto-grants-2013_07
Patent number
US08476286B2

Reaction notes

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