6-chloro-4-ethyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one → 6-chloro-4-ethyl-4-(4-cyanophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 19696Notes

Reaction equation

HRID 19696 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([CH2:25][CH3:26])[C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=1.[Cu][C:28]#[N:29]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([CH2:25][CH3:26])[C:18]1[CH:23]=[CH:22][C:21]([C:28]#[N:29])=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 118538166-chloro-4-ethyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 118538176-chloro-4-ethyl-4-(4-cyanophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
200 °C

Procedure

To a solution of 0.062 g (0.14 mmol) 6-chloro-4-ethyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one in 1 mL DMF was added 0.015 g (0.17 mmol) copper(I) cyanide and the mixture heated in a sealed tube at 200° C. for 2 hours. After cooling to room temperature, the mixture was filtered and the resulting DMF solution purified by preperative reverse phase chromatography (linear gradient 5 to 95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 SunFire 19×150 mm) to provide 6-chloro-4-ethyl-4-(4-cyanophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. 1H NMR (CDCl3, 400 MHz) δ 8.06 (s, NH); 7.71 (br d, 2H, J=8.24 Hz); 7.55 (br d, 2H, J=8.43 Hz); 7.14 (dd, 1H, J=8.61 and 2.20 Hz); 6.69 (d, 1H, J=8.61 Hz); 6.43 (d, 1H, J=2.02 Hz); 3.78 (dq, 1H, J=8.97 and 18 Hz); 3.60 (dq, 1H, J=8.43 and 17 Hz); 2.44 (dq, 1H, J=7.15 and 14 Hz); 2.27 (dq, 1H, J=7.14 and 14 Hz); 0.93 (t, J=7.15 Hz, 3H); MS (Electrospray): exact mass calculated for C19H15ClF3N3O+H 394.0929 found 394.0937

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. customthe resulting DMF solution purified by preperative reverse phase chromatography (linear gradient 5 to 95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 SunFire 19×150 mm)

Sources & evidence

ORD record
ord-507311387bb843d1a29d91dc3c94acfd
Source dataset
uspto-grants-2010_06
Patent number
US07745452B2

Reaction notes

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