Water → 4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-7-(3,4,5-trimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

HRID 517234Notes

Reaction equation

HRID 517234 reaction equation
CC(C)([O-])C.[Na+].[C:7]([C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:30]2[C:35](=O)[CH2:34][CH:33]([C:37]3[CH:42]=[C:41]([O:43][CH3:44])[C:40]([O:45][CH3:46])=[C:39]([O:47][CH3:48])[CH:38]=3)[CH2:32][C:31]=2[O:49]CC)[NH:16][C:17]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=2)=[O:18])=[CH:11][CH:10]=1)#[N:8].O>C(#N)C>[O:18]=[C:17]1[NH:16][CH:15]([C:12]2[CH:11]=[CH:10][C:9]([C:7]#[N:8])=[CH:14][CH:13]=2)[C:30]2[C:31](=[O:49])[CH2:32][CH:33]([C:37]3[CH:38]=[C:39]([O:47][CH3:48])[C:40]([O:45][CH3:46])=[C:41]([O:43][CH3:44])[CH:42]=3)[CH2:34][C:35]=2[N:19]1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:27])([F:28])[F:29])[CH:21]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23676156Sodium t-butoxideHCID 867323071-((4-Cyanophenyl)(2-ethoxy-6-oxo-4-(3,4,5-trimethoxyphenyl)cyclohex-1-enyl)-methyl)-3-(3-(trifluoromethyl)phenyl)urea2×

Product 1

HCID 867323554-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-7-(3,4,5-trimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Sodium tert-butoxide (126 mg, 1.32 mmol) is added to a solution of 1-((4-cyanophenyl)-(2-ethoxy-6-oxo-4-(3,4,5-trimethoxyphenyl)cyclohex-1-enyl)methyl)-3-(3-(trifluoromethyl)phenyl)urea (intermediate 19, 684 mg, 1.10 mmol) in acetonitrile (8 mL) and the mixture is stirred at room temperature for 2 h. Water is added and the mixture is extracted with ethyl acetate. The organic layer is dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 190 mg; ESI mass spectrum [M+H]+=578, Retention time HPLC: 1.13 min, 1.14 min (1:1 mixture of diastereomers) (V011_S01).

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. dry with materialThe organic layer is dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  5. additionESI mass spectrum [M+H]+=578, Retention time HPLC: 1.13 min, 1.14 min (1:1 mixture of diastereomers) (V011_S01)

Sources & evidence

ORD record
ord-8e99b40dd80b4c4bb7b3958341770aea
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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