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

HRID 480583Notes

Reaction equation

HRID 480583 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

36.02 g of 4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxy-6-nitroquinazoline are suspended in a mixture of 1080 ml of ethanol, 144 ml of glacial acetic acid, and 360 ml of water and refluxed, during which time the substance goes into solution. 20.70 g of iron powder are then carefully added in batches. After 30 minutes, the reaction is complete and the reaction mixture is evaporated to dryness. The residue is taken up in 1200 ml of methylene chloride/methanol (9:1) and made alkaline with 33% ammonia solution. The iron slurry is suction filtered through and washed with 500 ml of methylene chloride/methanol (9:1). The brown filtrate is filtered through a silica gel packing, washed with a total of 2000 ml of methylene chloride/methanol (9:1), and concentrated by evaporation. The flask residue is suspended with 140 ml of diethylether, suction filtered, and air dried. Yield: 29.70 g (89% of theory); melting point: 208° C.; mass spectrum (ESI+): m/z=359, 361 [M+H]+.

Workup

  1. temperaturerefluxed, during which time the substance
  2. customthe reaction mixture is evaporated to dryness
  3. filtrationfiltered through and
  4. washwashed with 500 ml of methylene chloride/methanol (9:1)
  5. filtrationThe brown filtrate is filtered through a silica gel packing
  6. washwashed with a total of 2000 ml of methylene chloride/methanol (9:1)
  7. concentrationconcentrated by evaporation
  8. filtrationfiltered
  9. customair dried

Sources & evidence

ORD record
ord-a32a76aadb72452ea2ac6af0e599e1e2
Source dataset
uspto-grants-2003_11
Patent number
US06653305B2

Reaction notes

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