Sodium hydride → HCID 18791578, compound

HRID 1005598Notes

Reaction equation

HRID 1005598 reaction equation
[OH:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]([CH3:31])[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=2[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[O:23])=[O:7])=[CH:4][C:3]=1[O:34][CH3:35].[H-].[Na+].[N+:38]([C:41]1[CH:48]=[CH:47][CH:46]=[CH:45][C:42]=1[CH2:43]Br)([O-:40])=[O:39]>CN(C)C=O>[CH3:35][O:34][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:2]=1[O:1][CH2:43][C:42]1[CH:45]=[CH:46][CH:47]=[CH:48][C:41]=1[N+:38]([O-:40])=[O:39])[C:6]([N:8]([CH3:31])[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=1[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)=[O:23])=[O:7]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 77569alpha-Bromo-2-nitrotolueneHCID 18791335HCID 18791335, compound

Product 1

HCID 18791578HCID 18791578, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-hydroxy-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]-benzamide (320 mg) in N,N-dimethylformamide (8 ml) was treated with sodium hydride (29.1 mg, 60% w/w in mineral oil) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes and then at ambient temperature for 10 minutes. o-Nitrobenzyl bromide (143 mg) was added, and the reaction mixture was stirred for 2.5 hours. The reaction was quenched with water and the mixture was diluted with ethyl acetate. The organic phase was washed with saturated aqueous sodium hydrogen carbonate, and brine. The organic solution was dried over magnesium sulfate, concentrated, and purified by silica gel column chromatography (SiO2 15 g, 3% methanol in dichloromethane) to give 3-methoxy-4-(2-nitrobenzyloxy)-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (210 mg).

Workup

  1. waitat ambient temperature for 10 minutes
  2. stirringthe reaction mixture was stirred for 2.5 hours
  3. customThe reaction was quenched with water
  4. additionthe mixture was diluted with ethyl acetate
  5. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate, and brine
  6. dry with materialThe organic solution was dried over magnesium sulfate
  7. concentrationconcentrated
  8. custompurified by silica gel column chromatography (SiO2 15 g, 3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a9c3a5c15edc4ac491fc231cb94a8f98
Source dataset
uspto-grants-2000_04
Patent number
US06054457

Reaction notes

Loading…