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

HRID 517280노트

반응식

HRID 517280 반응식
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[CH:12]1[C:21]2[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[C:14](=[O:33])[NH:13]1)[C:7]#[N:8].[CH3:34][S:35](Cl)(=[O:37])=[O:36].O>O1CCCC1>[Cl:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[CH:12]1[C:21]2[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:32])[F:30])[CH:24]=2)[C:14](=[O:33])[N:13]1[S:35]([CH3:34])(=[O:37])=[O:36])[C:7]#[N:8]

참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 867323963-Chloro-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

생성물 1

HCID 867324073-Chloro-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 8028Tetrahydrofuran용매

실험 절차

Sodium hydride (60% in mineral oil, 14 mg, 0.36 mmol) is added to a solution of 3-chloro-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 56, 60 mg, 0.13 mmol) in tetrahydrofuran (3 mL), and the mixture is stirred at room temperature for 20 min. Methanesulfonyl chloride (21 μL, 0.27 mmol) is added, and the mixture is stirred at room temperature over night. Water is added, and the mixture is extracted with dichloromethane. The phases are separated, and the organic phase is concentrated under reduced pressure. The residue is purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 40 mg; ESI mass spectrum [M+H]+=524; Retention time HPLC: 0.70 min (X012_S01).

후처리

  1. stirringthe mixture is stirred at room temperature over night
  2. extractionthe mixture is extracted with dichloromethane
  3. customThe phases are separated
  4. concentrationthe organic phase is concentrated under reduced pressure
  5. customThe residue is purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  6. custom0.70 min (X012_S01)

출처 및 근거

ORD 기록
ord-b3746630cac24955953a17ce4916c286
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115093B2

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