p-Toluenesulfonic acid → 6-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one

HRID 1498721

반응식

HRID 1498721 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[O:14]([CH2:22][CH2:23][O:24][C:25]1[C:32]([CH3:33])=[CH:31][C:28]([CH:29]=O)=[CH:27][C:26]=1[CH3:34])[Si](C(C)(C)C)(C)C.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C.CN(C=O)C.CO.[Pd]>[NH2:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[C:29]([C:28]1[CH:31]=[C:32]([CH3:33])[C:25]([O:24][CH2:23][CH2:22][OH:14])=[C:26]([CH3:34])[CH:27]=1)[NH:6][C:4]2=[O:5]

참가 물질

9

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 976652-Amino-5-nitrobenzamideHCID 23665763Sodium BisulfiteHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde

생성물 1

HCID 1363988506-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one수율 42%

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 31374Dimethylacetamide용매

반응 조건

온도
150 °C

실험 절차

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

후처리

  1. customThe solvent was evaporated under reduced pressure
  2. additionThe residue was diluted with water
  3. filtrationthe solids were filtered off
  4. customto give crude product (590 mg, 44%)
  5. filtrationThe reaction mixture was filtered
  6. customthe solvent was evaporated
  7. customto give crude product
  8. customThe crude was purified by column chromatography (silica gel 230-400 mesh; 4% methanol in CH2Cl2 as eluent)

출처 및 근거

ORD 기록
ord-4f09cecdee3f43c5aa94a3c937c8b2bc
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199990B2

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