Tetrahydrofuran → (S)-3-(Methylsulfonyl)-4-(3-(methylsulfonyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

HRID 517281노트

반응식

HRID 517281 반응식
[O:1]=[C:2]1[NH:11][C@H:10]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[S:20]([CH3:23])(=[O:22])=[O:21])[C:9]2[C:8](=[O:24])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]1[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1.[H-].[Na+].O1CCCC1.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>O>[CH3:23][S:20]([C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:12]=1[C@@H:10]1[C:9]2[C:8](=[O:24])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:33])([F:34])[F:32])[CH:26]=2)[C:2](=[O:1])[N:11]1[S:43]([CH3:42])(=[O:45])=[O:44])[C:16]#[N:17])(=[O:22])=[O:21]

참가 물질

6

반응물 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 86270877(S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

생성물 1

HCID 86732408(S)-3-(Methylsulfonyl)-4-(3-(methylsulfonyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

시약·촉매·용매 1

HCID 962Water용매

실험 절차

(S)-4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile (example 18A, 50 mg, 0.10 mmol) is added to a suspension of sodium hydride (60% in mineral oil, 11 mg, 0.29 mmol) and tetrahydrofuran (3 mL), and the mixture is stirred at room temperature for 10 min. Methanesulfonyl chloride (16 μL, 0.22 mol) is added, and the mixture is heated at 50° C. for 2 h. The mixture is cooled at room temperature, diluted with water (0.5 mL) and purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 37 mg; ESI mass spectrum [M+H]+=568; Retention time HPLC: 0.81 min (005_CA01).

후처리

  1. temperaturethe mixture is heated at 50° C. for 2 h
  2. temperatureThe mixture is cooled at room temperature
  3. custompurified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  4. custom0.81 min (005_CA01)

출처 및 근거

ORD 기록
ord-3ae070e6b71540fb8af6805456ab1781
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115093B2

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