p-Toluenesulfonic acid → 5-Chloro-2-(4-(4-isopropylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one

HRID 591657노트

반응식

HRID 591657 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([NH2:6])=[O:5].[CH:12]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=2)[CH2:17][CH2:16]1)([CH3:14])[CH3:13].CC1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CC(N(C)C)=O.C(Cl)Cl>[Cl:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:25]([C:24]1[CH:23]=[CH:22][C:21]([N:18]3[CH2:17][CH2:16][N:15]([CH:12]([CH3:14])[CH3:13])[CH2:20][CH2:19]3)=[CH:28][CH:27]=1)=[N:1]2

참가 물질

7

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 20522144-(4-Isopropylpiperazin-1-yl)benzaldehydeHCID 136759682-Amino-6-chlorobenzamideHCID 23665763Sodium Bisulfite

생성물 1

HCID 1362626555-Chloro-2-(4-(4-isopropylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 31374Dimethylacetamide용매

반응 조건

온도
140 °C

실험 절차

A solution of 2-amino-6-chlorobenzamide (0.314 g, 1.85 mmol) and 4-(4-isopropylpiperazin-1-yl)benzaldehyde (0.430 g, 1.85 mmol) in DMA (25 mL) were treated with p-TsOH (0.035 g, 0.185 mmol) and NaHSO3 (0.212 g, 2.04 mmol), and the mixture was heated at 140° C. for 18 hours. Then, the mixture was cooled, diluted with CH2Cl2 (200 mL), and washed with saturated NaHCO3 (100 mL). The organic phase was dried over anhydrous MgSO4, filtered, concentrated, and purified by silica gel chromatography, eluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 6:3:1 CHCl3/MeOH/concentrated NH4OH. The resulting solids were rechromatographed with 9:1 CH2Cl2/MeOH to afford the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6): δ 12.24 (br s, 1H), 8.11 (d, J=8.8 Hz, 2H), 7.66-7.71 (m, 1H), 7.59 (d, J=7.9 Hz, 1H), 7.42 (d, J=7.4 Hz, 1H), 7.03 (d, J=8.6 Hz, 2H), 3.28-3.34 (m, 4H), 2.64-2.73 (m, 1H), 2.55-2.59 (m, 4H), 1.01 (d, J=6.4 Hz, 6H). ESI MS m/z 383 [M+H]+.

후처리

  1. temperatureThen, the mixture was cooled
  2. washwashed with saturated NaHCO3 (100 mL)
  3. dry with materialThe organic phase was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography
  7. washeluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 6:3:1 CHCl3/MeOH/concentrated NH4OH
  8. customThe resulting solids were rechromatographed with 9:1 CH2Cl2/MeOH

출처 및 근거

ORD 기록
ord-3f72b1c43b9c49ec88bb5bc9e8acbffb
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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