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

HRID 1498741ノート

反応式

HRID 1498741 の反応式
[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]

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 31374Dimethylacetamide溶媒

反応条件

温度
155 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-ef327c28958c4de2a5aba14c2cfadf9a
出典データセット
uspto-grants-2015_12
特許番号
US09199990B2

反応ノート

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