Bis-(1H-imidazol-2-YL)-methanone → 3-(1-Benzylpiperidin-4-yl)-8-fluoro-3,4-dihydroquinazolin-2(1H)-one

HRID 2250277Notes

Reaction equation

HRID 2250277 reaction equation
[NH2:1][C:2]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][NH:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1.[C:24](C1NC=CN=1)(C1NC=CN=1)=[O:25]>O1CCCC1>[CH2:12]([N:9]1[CH2:10][CH2:11][CH:6]([N:5]2[CH2:4][C:3]3[C:2](=[C:22]([F:23])[CH:21]=[CH:20][CH:19]=3)[NH:1][C:24]2=[O:25])[CH2:7][CH2:8]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 21102226N-(2-Amino-3-fluorobenzyl)-1-benzylpiperidin-4-amine

Product 1

HCID 211021543-(1-Benzylpiperidin-4-yl)-8-fluoro-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(2-amino-3-fluorobenzyl)-1-benzylpiperidin-4-amine (36.3 g, 116 mmol) in tetrahydrofuran (600 mL) at room temperature was added carbonyl diimidazole (20.7 g, 1.10 equiv.) in one portion. The reaction was stirred at room temperature for 3 h, heated at reflux for 30 min, and concentrated. The resulting solid was dissolved in 1:1 diethyl ether/ethyl acetate, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated to give the crude product as a wet, yellow solid. The solid was triturated with diethyl ether and filtered to give 30.0 g (76%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 1.68 (m, 2H), 1.86 (dddd, J=11.9, 11.9, 11.9, 3.4, 2H), 2.14 (dd, J=11.6, 10.1, 2H), 2.98 (d, J=11.6, 2H), 3.51 (s, 2H), 4.34-4.44 (m, 3H), 6.71 (bs, 1H), 6.79-6.89 (m, 2H), 6.94 (dd, J=9.2, 9.2, 1H), 7.21-7.34 (m, 5H). Mass spec.: 340.30 (MH)+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 min
  3. concentrationconcentrated
  4. dissolutionThe resulting solid was dissolved in 1:1 diethyl ether/ethyl acetate
  5. washwashed with water (3×)
  6. dry with materialbrine, dried over magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a7e926c89765442a932bd7405bae0d2e
Source dataset
uspto-grants-2008_01
Patent number
US07314883B2

Reaction notes

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