p-Toluenesulfonic acid → 2-(2-((Dimethylamino)methyl)-1H-indol-5-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591702노트

반응식

HRID 591702 반응식
[CH3:1][N:2]([CH2:4][C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([CH:14]=O)=[CH:9][CH:8]=2)[CH3:3].[NH2:16][C:17]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[C:18]=1[C:19]([NH2:21])=[O:20].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:3][N:2]([CH2:4][C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([C:14]1[NH:21][C:19](=[O:20])[C:18]3[C:17](=[CH:25][C:24]([O:26][CH3:27])=[CH:23][C:22]=3[O:28][CH3:29])[N:16]=1)=[CH:9][CH:8]=2)[CH3:1]

참가 물질

6

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620322-dimethylaminomethyl-1H-indole-5-carbaldehyde

생성물 1

HCID 1359390422-(2-((Dimethylamino)methyl)-1H-indol-5-yl)-5,7-dimethoxyquinazolin-4(3H)-one

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
120 °C

실험 절차

To a solution of 2-dimethylaminomethyl-1H-indole-5-carbaldehyde (0.88 g crude, 4.35 mmol) and 2-amino-4,6-dimethoxy-benzamide (0.85 g, 4.35 mmol) in N,N-dimethylacetamide (15 mL) were added sodium hydrogen sulfite (58.5 wt %, 0.95 g, 5.22 mmol) and p-toluenesulfonic acid (0.99 g, 5.22 mmol). The reaction mixture was stirred at 120° C. for 5 hours under nitrogen, then cooled to room temperature, and concentrated under reduced pressure. 30% aqueous sodium carbonate (50 mL) was then added. The separated solid was filtered, washed with water (50 mL), and dried under vacuum. Crude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 7 N ammonia in methanol 5% in CH2Cl2 as eluent) to give the title compound as an off-white solid. Yield: 0.83 g (50%). MP 187-188° C. 1H NMR (400 MHz, DMSO-d6): δ 11.82 (s, 1H), 11.34 (s, 1H), 8.38 (s, 1H), 7.93 (d, J=8.59 Hz, 1H), 7.40 (d, J=8.59 Hz, 1H), 6.73 (s, 1H), 6.49 (s, 1H), 6.40 (s, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.57 (s, 2H), 2.21 (s, 6H).

후처리

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. addition30% aqueous sodium carbonate (50 mL) was then added
  4. filtrationThe separated solid was filtered
  5. washwashed with water (50 mL)
  6. customdried under vacuum
  7. customCrude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 7 N ammonia in methanol 5% in CH2Cl2 as eluent)

출처 및 근거

ORD 기록
ord-e70bb02dfda941609b4523109f91e97b
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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