p-Toluenesulfonic acid → 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one

HRID 1498741노트

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HRID 1498741 반응식
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[C:3]=1[C:4]([NH2:6])=[O:5].C([Si](C)(C)[O:18][CH2:19][CH2:20][O:21][C:22]1[C:29]([CH3:30])=[CH:28][C:25]([CH:26]=O)=[CH:24][C:23]=1[CH3:31])(C)(C)C.S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C)C(=O)C.O.C1COCC1.CO>[OH:18][CH2:19][CH2:20][O:21][C:22]1[C:29]([CH3:30])=[CH:28][C:25]([C:26]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][C:7]=3[CH3:12])[N:1]=2)=[CH:24][C:23]=1[CH3:31]

참가 물질

10

반응물 5

HCID 6101p-Toluenesulfonic acidHCID 2724141Tetrabutylammonium FluorideHCID 23665763Sodium BisulfiteHCID 666613962-Amino-4,6-dimethylbenzamideHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde

생성물 1

HCID 1359079412-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one수율 24%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 31374Dimethylacetamide용매

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온도
155 °C

실험 절차

A mixture of 2-amino-4,6-dimethylbenzamide (0.2 g, 1.22 mmol), 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,5-dimethyl-benzaldehyde (0.376 g, 1.22 mmol), sodium hydrogensulfite (0.22 g, 1.22 mmol) and p-toluenesulfonic acid (0.116 g, 0.61 mmol) in N,N-dimethyl acetamide (10 mL) was stirred at 155° C. for 14 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL). The solid crashed out and was collected by filtration to afford impure product. The solid was re-dissolved in THF (30 mL) and mixed with TBAF in THF (5 mL, 5 mmol). The reaction mixture was stirred at room temperature for 14 h and concentrated using a rotary evaporator to afford an oily residue. Further purification by column (SiO2, EtOAc/DCM/MeOH=12:4:1) yielded an off-white solid. This solid was diluted with MeOH (10 mL) to make a slurry. The solid was collected by filtration and washed with MeOH to afford 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one (98 mg, 24%) as a white solid. Selected data: MS (ES) m/z: 339.10; MP 259.6-261.2° C.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationwas collected by filtration
  3. customto afford impure product
  4. stirringThe reaction mixture was stirred at room temperature for 14 h
  5. concentrationconcentrated
  6. customa rotary evaporator
  7. customto afford an oily residue
  8. customFurther purification by column (SiO2, EtOAc/DCM/MeOH=12:4:1)
  9. customyielded an off-white solid
  10. filtrationThe solid was collected by filtration
  11. washwashed with MeOH

출처 및 근거

ORD 기록
ord-ef327c28958c4de2a5aba14c2cfadf9a
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199990B2

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