Dimethyl Sulfide → [5,6-Difluoro-4-(4-fluorophenyl)-2-oxo-3-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroquinazolin-4-yl]acetaldehyde

HRID 19688Notes

Reaction equation

HRID 19688 reaction equation
[CH2:1]([C:4]1([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:15])[C:12]=2[F:14])[NH:7][C:6](=[O:16])[N:5]1[CH2:17][C:18]([F:21])([F:20])[F:19])[CH:2]=C.[O:29]=[O+][O-].CSC>CO.CCOC(C)=O>[F:14][C:12]1[C:11]([F:15])=[CH:10][CH:9]=[C:8]2[C:13]=1[C:4]([CH2:1][CH:2]=[O:29])([C:22]1[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=1)[N:5]([CH2:17][C:18]([F:21])([F:19])[F:20])[C:6](=[O:16])[NH:7]2

Participants

6

Reactant 3

HCID 1068Dimethyl SulfideHCID 24823OzoneHCID 118538134-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Product 1

HCID 86621312[5,6-Difluoro-4-(4-fluorophenyl)-2-oxo-3-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroquinazolin-4-yl]acetaldehyde

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a −78° C. solution of 2.6 g (6.495 mmol) 4-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one in 25 ml MeOH was bubbled ozone. After 15 mins at −78° C., the ozone was removed and the reaction mixture was quenched with 4.8 mL (64.946 mmol) dimethyl sulfide. After stirring at room temperature overnight, the reaction mixture was diluted with EtOAc and washed three times with water and brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Afforded [5,6-difluoro-4-(4-fluorophenyl)-2-oxo-3-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroquinazolin-4-yl]acetaldehyde. 1H NMR (CDCl3, 400 MHz) δ 9.79 (s, 1H, O═CH); 8.61 (br s, 1H, ArNHC═O); 7.38-7.27 (m, 2H, ArH); 7.15-7.03 (m, 3H, ArH); 6.57-6.53 (m, 1H, ArH); 4.08 (m, 1H, C); 3.72 (dd, 1H, J=17.4 Hz, CH2C═O); 3.50 (dd, 1H J=1.28 Hz, 17.58 Hz, CH2C═O); 3.32 (m, 1H, CH2C═O). ES MS+1=403.1.

Workup

  1. customthe ozone was removed
  2. washwashed three times with water and brine
  3. dry with materialThe organic layer was dried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-74eae65960864069a122f877c9fbc7db
Source dataset
uspto-grants-2010_06
Patent number
US07745452B2

Reaction notes

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