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

HRID 244526노트

반응식

HRID 244526 반응식
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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 3283Diethyl Ether용매2회HCID 3776Isopropanol용매HCID 6342Acetonitrile용매

실험 절차

4-Chloro-6-(methyloxy)-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+).

후처리

  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

출처 및 근거

ORD 기록
ord-0b28319401fe4355a312ec9448ac535d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658654B2

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