p-Toluenesulfonic acid → N-(1-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)pyrrolidin-3-yl)-N-methylacetamide

HRID 591665노트

반응식

HRID 591665 반응식
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:27][CH2:26][CH:25]([N:28]([CH3:32])[C:29](=[O:31])[CH3:30])[CH2:24]2)=[CH:19][CH:18]=1)=O.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O.C(Cl)Cl>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:15]([C:17]1[CH:18]=[CH:19][C:20]([N:23]3[CH2:27][CH2:26][CH:25]([N:28]([CH3:32])[C:29](=[O:31])[CH3:30])[CH2:24]3)=[CH:21][CH:22]=1)=[N:1]2

참가 물질

7

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86662025N-(1-(4-formylphenyl)pyrrolidin-3-yl)-N-methylacetamide

생성물 1

HCID 136262660N-(1-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)pyrrolidin-3-yl)-N-methylacetamide수율 88%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 31374Dimethylacetamide용매

반응 조건

온도
150 °C

실험 절차

A solution of 2-amino-4,6-dimethoxybenzamide (0.797 g, 4.07 mmol) and N-(1-(4-formylphenyl)pyrrolidin-3-yl)-N-methylacetamide (1.0 g, 4.07 mmol) in DMA (75 mL) was treated with NaHSO3 (0.466 g, 4.5 mmol) and p-TsOH (0.078 g, 0.41 mmol). The mixture was heated at 150° C. for 15 hours, cooled to room temperature, diluted with CH2Cl2 (200 mL), and washed with saturated NaHCO3 (100 mL) and water (200 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH, to afford the title compound (1.5 g, 88%) as a light brown solid. 1H NMR (300 MHz, DMSO-d6): δ 11.68 (s, 1H), 8.10 (d, J=8.8 Hz, 2H), 6.55-6.67 (m, 3H), 6.44 (d, J=2.2 Hz, 1H), 4.67-5.22 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.43-3.60 (m, 2H), 3.22-3.26 (m, 2H), 2.76-2.89 (m, 3H), 1.91-2.27 (m, 5H). ESI MS m/z 423 [M+H]+.

후처리

  1. temperaturecooled to room temperature
  2. washwashed with saturated NaHCO3 (100 mL) and water (200 mL)
  3. dry with materialThe organic phase was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel
  7. washeluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH

출처 및 근거

ORD 기록
ord-b28d6c7410db4628bcffd543c8d23e9f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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