Sodium hydride → HCID 9847731, compound

HRID 855708Notes

Reaction equation

HRID 855708 reaction equation
[C:1]1([C:7]2[CH2:11][C:10](=[O:12])[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1>CN(C=O)C.[Cl-].[NH4+]>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:28][CH2:29][CH2:30][CH2:31][N:32]1[CH2:33][CH2:34][N:35]([CH3:38])[CH2:36][CH2:37]1)[N:19]=[CH:18][N:17]=[C:16]2[O:12][C:10]1[CH:11]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[NH:8][N:9]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 785775-Phenyl-4H-pyrazol-3-olHCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline

Product 1

HCID 9847731HCID 9847731, compoundYield 76.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

3-Phenyl-4,5-dihydro-1H-pyrazol-5-one (182 mg, 1.14 mmol), (J. Org. Chem., 1967, 32, 3321-3324), was added in portions to a suspension of sodium hydride (46 mg, 1.14 mmol, prewashed with pentane) in DMF (3 ml). After stirring for 30 minutes at ambient temperature, 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (200 mg, 0.57 mmol) was added. The mixture was stirred for 30 minutes at 60° C. After cooling, the mixture was diluted with saturated aqueous ammonium chloride solution and partitioned between ethyl acetate and water. The organic layer was passed through an ISOLUTE (trade mark of IST) SPE column. The column was thoroughly washed with methanol. The product was recovered from the column by washing with a mixture of 0.1M solution of ammonia in methylene chloride/methanol (1/1). The volatiles were removed by evaporation and the solid was collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-4-(5-phenylpyrazol-3-yloxy)quinazoline (206 mg, 76%).

Workup

  1. stirringThe mixture was stirred for 30 minutes at 60° C
  2. temperatureAfter cooling
  3. custompartitioned between ethyl acetate and water
  4. washThe column was thoroughly washed with methanol
  5. customThe product was recovered from the column
  6. washby washing with a mixture of 0.1M solution of ammonia in methylene chloride/methanol (1/1)
  7. customThe volatiles were removed by evaporation
  8. filtrationthe solid was collected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-e956258bd3e3478e94028f4ff387af88
Source dataset
uspto-grants-2007_08
Patent number
US07262201B1

Reaction notes

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