Hydrochloric Acid → 4-(3,4-Dichloroanilino)-6-methoxyquinazolin-7(1H)-one

HRID 2102424Notes

Reaction equation

HRID 2102424 reaction equation
Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15]CC3C=CC=CC=3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][C:30]=1[Cl:31])[NH2:27].Cl>C(O)(C)C.C(OCC)C.C(#N)C>[Cl:23][C:24]1[CH:25]=[C:26]([NH:27][C:3]2[C:12]3[C:7](=[CH:8][C:9]([OH:15])=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)[CH:28]=[CH:29][C:30]=1[Cl:31]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 72573,4-DichloroanilineHCID 220308367-(Benzyloxy)-4-chloro-6-methoxyquinazoline hydrochloride

Product 1

HCID 1362726214-(3,4-Dichloroanilino)-6-methoxyquinazolin-7(1H)-oneYield 94.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

4-Chloro-6-(methyl-oxy)-7-[(phenylmethyl)oxy]quinazoline hydrochloride (22.91 g, 67.9 mmol) was suspended in isopropanol followed by addition of 3,4-dichloroaniline (13.2 g, 81.5 mmol) and concentrated aqueous hydrochloric acid (1 mL). The mixture was brought to reflux over 12 hours and diluted with ethyl ether (150 mL). The solid was collected by filtration, washed with additional ethyl ether and dried. The material was then taken into trifluoroacetic acid (150 mL) and brought to reflux over 1 hour. The solution was cooled to room temperature then concentrated in vacuo to give a crystalline residue. The residue was suspended in acetonitrile (100 mL) followed by addition of ethyl ether (100 mL). The solid was collected by filtration and washed with additional ethyl ether then dried in vacuo to give 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol (21.49 g, 64% yield) as a tan solid. 1H NMR (400 MHz, d6-DMSO): 11.09 (br s, 1H), 8.87 (s, 1H), 8.07 (d, 1H), 8.00 (s, 1H), 7.23 (s, 1H), 3.98 (s, 3H); MS (EI) for C15H11N3O2Cl2: 337 (MH+).

Workup

  1. temperatureto reflux over 12 hours
  2. filtrationThe solid was collected by filtration
  3. washwashed with additional ethyl ether
  4. customdried
  5. temperatureto reflux over 1 hour
  6. concentrationthen concentrated in vacuo
  7. customto give a crystalline residue
  8. filtrationThe solid was collected by filtration
  9. washwashed with additional ethyl ether
  10. customthen dried in vacuo

Sources & evidence

ORD record
ord-590e8f5aec944f5983e182ac6b8fa406
Source dataset
uspto-grants-2009_08
Patent number
US07576074B2

Reaction notes

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