Acetic Anhydride → N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide

HRID 1498722

反応式

HRID 1498722 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([O:19][CH2:20][CH2:21][OH:22])=[C:14]([CH3:23])[CH:13]=1)[NH:6][C:5]2=[O:24].[C:25](OC(=O)C)(=[O:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1>[OH:22][CH2:21][CH2:20][O:19][C:15]1[C:16]([CH3:18])=[CH:17][C:12]([C:7]2[NH:6][C:5](=[O:24])[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:25](=[O:27])[CH3:26])[CH:3]=3)[N:8]=2)=[CH:13][C:14]=1[CH3:23]

参加物

5

反応物 3

HCID 7918Acetic AnhydrideHCID 11430Potassium CarbonateHCID 1363988506-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one

生成物 1

HCID 136038013N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

To a solution of 2-amino-5-nitro-benzamide (680 mg, 3.75 mmol) and 4-[2-(tert-butyldimethylsilanoxy) ethoxy]-3,5-dimethylbenzaldehyde (1.16 g, 3.75 mmol) in N,N-dimethyl acetamide (35 mL), NaHSO3 (736 mg, 4.14 mmol) and p-TSA (71 mg, 0.375 mmol) were added and the reaction mixture was heated at 150° C. for 5 h. The solvent was evaporated under reduced pressure. The residue was diluted with water and the solids were filtered off to give crude product (590 mg, 44%). To a solution of above crude product (490 mg, 1.38 mmol) in DMF (20 mL) and MeOH (20 mL), Pd—C (100 mg, 10%) was added and the reaction mixture was hydrogenated for 4 h at room temperature at 30 psi H2. The reaction mixture was filtered and the solvent was evaporated to give crude product. The crude was purified by column chromatography (silica gel 230-400 mesh; 4% methanol in CH2Cl2 as eluent) to give 6-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one (190 mg, 42% yield). To a solution of 6-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one (95 mg, 0.29 mmol) in pyridine (5 mL), acetic anhydride (108 mg, 0.73 mmol) was added and the mixture was stirred for 16 h at room temperature. The solvent was removed and the solids were dissolved in a mixture of MeOH (10 mL) and THF (10 mL) (compound was partially soluble). Then K2CO3 (100 mg, 0.73 mmol) was added and the reaction mixture was stirred for 3 h at room temperature. The solvent was removed and the crude was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in CH2Cl2 as eluent) to give N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide

後処理

  1. customThe solvent was removed
  2. dissolutionthe solids were dissolved in a mixture of MeOH (10 mL) and THF (10 mL) (compound
  3. stirringthe reaction mixture was stirred for 3 h at room temperature
  4. customThe solvent was removed
  5. customthe crude was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in CH2Cl2 as eluent)

出典と根拠

ORDレコード
ord-5444f959d8c94c41b153c127ad190a6c
出典データセット
uspto-grants-2015_12
特許番号
US09199990B2

関連ノート

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