p-Toluenesulfonic acid → 2-(4-((3R,5S)-4-Isopropyl-3,5-dimethylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591659노트

반응식

HRID 591659 반응식
[CH:1]([N:4]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)[CH2:6][CH:5]1[CH3:19])([CH3:3])[CH3:2].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:36][C:37]1[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[C:38]=1[C:39]([NH2:41])=[O:40]>CC(N(C)C)=O.O>[CH:1]([N:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:18]=[CH:17][C:14]([C:15]3[NH:41][C:39](=[O:40])[C:38]4[C:37](=[CH:45][C:44]([O:46][CH3:47])=[CH:43][C:42]=4[O:48][CH3:49])[N:36]=3)=[CH:13][CH:12]=2)[CH2:6][C@H:5]1[CH3:19])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620244-(4-Isopropyl-3,5-dimethylpiperazin-1-yl)benzaldehyde

생성물 1

HCID 1362626562-(4-((3R,5S)-4-Isopropyl-3,5-dimethylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one수율 17.4%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

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온도
140 °C

실험 절차

A mixture of 4-(4-isopropyl-3,5-dimethylpiperazin-1-yl)benzaldehyde (0.400 g, 1.50 mmol), NaHSO3 (0.195 g, 1.80 mmol), and p-TsOH (0.030 g, 0.15 mmol) was added to a solution of 2-amino-4,6-dimethoxybenzamide (0.400 g, 2.40 mmol) in DMA (10 mL). The reaction was stirred at 140° C. for 4 hours, then at room temperature overnight. The mixture was diluted with H2O and extracted with CH2Cl2. The organics were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 1% to 10% MeOH/CH2Cl2, followed by reverse-phase chromatography, eluting with 10% to 90% CH3CN in H2O, afforded the title compound (0.114 g, 17%). 1H NMR (300 MHz, DMSO-d6): δ 11.68 (s, 1H), 8.09 (d, J=8.9 Hz, 2H), 6.78 (d, J=9.0 Hz, 2H), 6.66 (s, 1H), 6.44 (s, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.41-3.44 (m, 2H), 3.11-3.23 (m, 5H), 1.00-1.03 (m, 12H). ESI MS m/z 437 [M+H]+.

후처리

  1. customat room temperature
  2. customovernight
  3. extractionextracted with CH2Cl2
  4. washThe organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel
  9. washeluting with 1% to 10% MeOH/CH2Cl2
  10. washeluting with 10% to 90% CH3CN in H2O

출처 및 근거

ORD 기록
ord-826f31a2a8a3474e92a2a1941ba96671
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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