Ethanol → 4-[(3,4-Dichloro-6-fluorophenyl)amino]-6-aminoquinazoline

HRID 411948Notes

Reaction equation

HRID 411948 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([N+:21]([O-])=O)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[C:5]([F:9])=[CH:6][C:7]=1[Cl:8].C(O)C.O.O.NN>[Ni].C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([NH2:21])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[C:5]([F:9])=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 962WaterHCID 24654Hydrazine hydrate (1:1)2×HCID 154809984-[(3,4-Dichloro-6-fluorophenyl)amino]-6-nitroquinazoline

Product 1

HCID 115443254-[(3,4-Dichloro-6-fluorophenyl)amino]-6-aminoquinazoline

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 3776IsopropanolSolvent

Procedure

A solution of 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline (1.09 mmol) in 18 ml 9:1 ethanol:water and 11 ml iso-propylalcohol was heated to reflux temperature. 250 μl hydrazine hydrate and 0.5 ml Raney®Nickel (in water) were added thereafter. After 30 minutes, additional 50 μl of hydrazine hydrate was added, and the reflux was maintained for 20 minutes. Filtration, evaporation and silica gel chromatography (using 90% CH2Cl2/10% MeOH as elute) gave 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline (compound 2) in 75% yield.

Workup

  1. temperatureto reflux temperature
  2. temperaturethe reflux was maintained for 20 minutes
  3. filtrationFiltration, evaporation and silica gel chromatography (using 90% CH2Cl2/10% MeOH as elute)

Sources & evidence

ORD record
ord-844aa7f08e5f44b1859549839c9092ee
Source dataset
uspto-grants-2003_05
Patent number
US06562319B2

Reaction notes

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