4-allyl-6-chloro-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one → 6-chloro-4-propyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 19705Notes

Reaction equation

HRID 19705 reaction equation
[CH2:1]([C:4]1([C:21]([F:24])([F:23])[F:22])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([Cl:14])[CH:12]=2)[NH:7][C:6](=[O:15])[N:5]1[CH2:16][C:17]([F:20])([F:19])[F:18])[CH:2]=[CH2:3]>[Pd].C(OCC)(=O)C>[Cl:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:15])[N:5]([CH2:16][C:17]([F:20])([F:19])[F:18])[C:4]2([CH2:1][CH2:2][CH3:3])[C:21]([F:23])([F:24])[F:22]

Participants

4

Reactant 1

HCID 118540754-allyl-6-chloro-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one

Product 1

HCID 118540766-chloro-4-propyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-allyl-6-chloro-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one (42 mg, 0.11 mmol), ethyl acetate (3.5 ml) and 10% Pd/C (10 mg) was placed under hydrogen atmosphere (1 atm) at room temperature and stirred overnight. After bubbling nitrogen through reaction mixture, the mixture was filtered through a Celite, washing with ethyl acetate. The collected filtrate was concentrated to give an oil which was purified by reverse phase prep HPLC to afford 6-chloro-4-propyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one as a white solid. 1H NMR (CD3OD, 400 MHz) δ 7.40 (s, 1H), 7.35 (dd, J=2.4 and 8.6 Hz, 1H), 6.86 (d, J=8.8 Hz 1H), 4.45 (m, 1H), 4.27 (m, 1H), 2.47 (m, 1H), 2.17 (m, 1H), 1.23 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

Workup

  1. customat room temperature
  2. customAfter bubbling nitrogen
  3. customthrough reaction mixture
  4. filtrationthe mixture was filtered through a Celite
  5. washwashing with ethyl acetate
  6. concentrationThe collected filtrate was concentrated
  7. customto give an oil which
  8. customwas purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-70e32520aad54423abb9a53826592e38
Source dataset
uspto-grants-2010_06
Patent number
US07745452B2

Reaction notes

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