Sodium Hydroxide → 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one

HRID 394110Notes

Reaction equation

HRID 394110 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:18]=[C:17]([CH2:19][N:20]2[CH2:25][CH:24]3[CH2:26][CH:21]2[CH2:22][N:23]3[CH:27]([CH3:29])[CH3:28])[CH:16]=[C:15]2[C:10]=1[CH2:11][N:12](CC1C=CC(OC)=CC=1)[C:13](=[O:38])[N:14]2[C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:37].[OH-].[Na+]>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:18]=[C:17]([CH2:19][N:20]2[CH2:25][CH:24]3[CH2:26][CH:21]2[CH2:22][N:23]3[CH:27]([CH3:29])[CH3:28])[CH:16]=[C:15]2[C:10]=1[CH2:11][NH:12][C:13](=[O:38])[N:14]2[C:30]1[C:31]([Cl:37])=[CH:32][CH:33]=[CH:34][C:35]=1[Cl:36]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 226478785-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one

Product 1

HCID 101446985-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

The solution of 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (136 mg, 0.20 mmol) in trifluoroacetic acid (1.5 mL) was stirred at 60° C. for 1 h. It was cooled to rt and treated with 5N NaOH solution to pH 9˜10. The resulting mixture was extracted with methylene chloride. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by preparative thin layer chromatography using 8% of 2N ammonium in methanol/methylene chloride as eluent provided the 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one as a white solid. 1H NMR (CDCl3, 500 MHz): δ 1.03 (d, 3H, J=5.7 Hz), 1.08 (d, 3H, J=5.7 Hz), 1.66 (m, 2H), 2.37 (t, 1H, J=8.2 Hz), 2.43 (t, 1H, J=11.9 Hz), 2.56 (brs, 1H), 2.83 (t, 1H, J=9.2 Hz), 2.90 (d, 1H, J=8.7 Hz), 3.14 (s, 1H), 3.54 (m, 2H), 3.64 (t, 1H, J=13.0 Hz), 4.33 (abq, 2H, J=14.2 Hz), 5.12 (s, 1H), 6.24 (s, 1H), 6.84 (s, 1H), 7.08 (t, 1H, J=8.0 Hz), 7.28 (m, 2H), 7.39 (d, 1H, J=8.0 Hz), 7.54 (t, 1H, J=8.0 Hz). MS (API-ES+): 573 (M+H).

Workup

  1. extractionThe resulting mixture was extracted with methylene chloride
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography

Sources & evidence

ORD record
ord-1dfba410e6be4b75b8709dcbb105ca6b
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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