3,5-Dimethyl-4-hydroxybenzaldehyde → 2-(4-hydroxy-3,5-dimethyl-phenyl)-6-nitro-3H-quinazolin-4-one

HRID 1498689

반응식

HRID 1498689 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[OH:14][C:15]1[C:22]([CH3:23])=[CH:21][C:18]([CH:19]=O)=[CH:17][C:16]=1[CH3:24].S(=O)(O)[O-].[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.CN(C)C(=O)C>[OH:14][C:15]1[C:22]([CH3:23])=[CH:21][C:18]([C:19]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][CH:9]=[C:8]([N+:11]([O-:13])=[O:12])[CH:7]=3)[N:1]=2)=[CH:17][C:16]=1[CH3:24]

참가 물질

7

반응물 4

HCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 976652-Amino-5-nitrobenzamideHCID 521998p-Toluenesulfonic acid monohydrateHCID 23665763Sodium Bisulfite

생성물 1

HCID 1363988412-(4-hydroxy-3,5-dimethyl-phenyl)-6-nitro-3H-quinazolin-4-one수율 19%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

반응 조건

온도
155 °C

실험 절차

To a round-bottomed flask were added 2-amino-5-nitro-benzamide (0.681 g, 3.76 mmol), 4-hydroxy-3,5-dimethyl-benzaldehyde (0.565 g, 3.76 mmol), sodium bisulfite (0.747 g, 4.2 mmol), p-toluenesulfonic acid, monohydrate (0.072 g, 0.376 mmol) and N,N-dimethylacetamide (60 mL). The reaction mixture was refluxed at 155° C. for 16 h before being cooled to room temperature. Water was added and the precipitated solid was filtered off, washed with water and methanol to obtain a crude which was purified by column chromatography (silica gel (50 g) employing 1-20% methanol in dichloromethane as eluents, to obtain 2-(4-hydroxy-3,5-dimethyl-phenyl)-6-nitro-3H-quinazolin-4-one (0.220 g, 19%). The compound 2-(4-hydroxy-3,5-dimethyl-phenyl)-6-nitro-3H-quinazolin-4-one (0.220 g, 0.71 mmol) was hydrogenated in dimethyl formamide (20 mL) using palladium on activated carbon (0.076 g, 0.071 mmol) at room temperature for 14 h. The solvent was evaporated and the crude was purified by column chromatography (silica gel 25 g) employing 1-5% methanol in dichloromethane as eluents to obtain 6-amino-2-(4-hydroxy-3,5-dimethyl-phenyl)-3H-quinazolin-4-one (0.132 g). The compound 6-amino-2-(4-hydroxy-3,5-dimethyl-phenyl)-3H-quinazolin-4-one was dissolved in pyridine under nitrogen. Acetic anhydride was added at room temperature and stirred for 4 h. Pyridine was removed and the residue was dried. Methanol was added to the flask and a solution of potassium carbonate in water was added and stirred for 4 h. The solvent was removed, acidified with 1 N hydrochloric acid and the precipitated solid was filtered off and dried to obtain N-(2-(4-hydroxy-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide (0.037 g, 17%). Selected data: MS (ES) m/z: 324.1; MP 336.5° C. (decomposed).

후처리

  1. temperaturebefore being cooled to room temperature
  2. filtrationthe precipitated solid was filtered off
  3. washwashed with water and methanol
  4. customto obtain a crude which
  5. customwas purified by column chromatography (silica gel (50 g)

출처 및 근거

ORD 기록
ord-7b83d458f34c4f0f850fe0361738a96d
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199990B2

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