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 517281Notes

Reaction equation

HRID 517281 reaction equation
[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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-3ae070e6b71540fb8af6805456ab1781
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

Loading…