Tetrahydrofuran → HCID 86732409, compound

HRID 517282Notes

Reaction equation

HRID 517282 reaction equation
[O:1]=[C:2]1[NH:11][CH:10]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:20])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]1[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1.[H-].[Na+].O1CCCC1.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>O.C(#N)C.C(O)(=O)C>[CH3:38][S:39]([N:11]1[CH:10]([C:12]2[CH:13]=[CH:14][C:15]([C:16]#[N:17])=[CH:18][CH:19]=2)[C:9]2[C:8](=[O:20])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]([C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:2]1=[O:1])(=[O:41])=[O:40]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 86732405HCID 86732405, compound

Product 1

HCID 86732409HCID 86732409, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

4-(2,5-Dioxo-1-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile (example 14, 40 mg, 97 μmol) is added to a mixture of sodium hydride (60% in mineral oil, 15 mg, 0.19 mmol) and tetrahydrofuran (1 mL), and the mixture is stirred at room temperature for 3 min. Methanesulfonyl chloride (15 μL, 0.19 mmol) is added, and the mixture is heated at 50° C. for 1 h. The mixture is cooled at room temperature, diluted with water, acetonitrile and acetic acid and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 32 mg; ESI mass spectrum [M+H]+=491; Retention time HPLC: 1.01 min (Z018_S04).

Workup

  1. temperaturethe mixture is heated at 50° C. for 1 h
  2. temperatureThe mixture is cooled at room temperature
  3. custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  4. custom1.01 min (Z018_S04)

Sources & evidence

ORD record
ord-0326fb34157d4c94a7087400a2fa9866
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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