Acetic Acid → 6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxyquinazoline

HRID 1168690Notes

Reaction equation

HRID 1168690 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH:25]4[CH2:27][CH2:26]4)=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(O)(=O)C.O>C(O)C.[Fe]>[NH2:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][C:16]=1[O:23][CH2:24][CH:25]1[CH2:27][CH2:26]1)[N:13]=[CH:12][N:11]=[C:10]2[NH:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 15541851N-(3-chloro-4-fluorophenyl)-7-(cyclopropylmethoxy)-6-nitroquinazolin-4-amine

Product 1

HCID 155418526-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxyquinazoline

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

30.00 g of 4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxy-6-nitroquinazoline are suspended in a mixture of 900 ml of ethanol, 120 ml of glacial acetic acid, and 300 ml of water. The suspension is refluxed, producing a clear solution. 17.24 g of iron powder is then carefully added batchwise, while the reaction mixture effervesces each time. About 15 minutes after it has all been added, a precipitate is formed. The reaction mixture is stirred for a further 15 minutes and then evaporated to dryness in vacuo. The residue in the flask is taken up in 1000 ml of methylene chloride/methanol (9:1) and combined with 30 ml of 33% aqueous ammonia solution. The iron slurry is filtered off and washed with methylene chloride:methanol (9:1). The brown filtrate is filtered through a silica gel pack and evaporated to dryness. The residue in the flask is stirred with 60 ml of diethylether, suction filtered and dried in the air.

Workup

  1. temperatureThe suspension is refluxed
  2. customproducing a clear solution
  3. additionall been added
  4. customa precipitate is formed
  5. customevaporated to dryness in vacuo
  6. filtrationThe iron slurry is filtered off
  7. washwashed with methylene chloride:methanol (9:1)
  8. filtrationThe brown filtrate is filtered through a silica gel pack
  9. customevaporated to dryness
  10. stirringThe residue in the flask is stirred with 60 ml of diethylether, suction
  11. filtrationfiltered
  12. customdried in the air

Sources & evidence

ORD record
ord-1eccc58ffae84f768aac3a5fe745ae09
Source dataset
uspto-grants-2003_09
Patent number
US06627634B2

Reaction notes

Loading…