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

HRID 2099731Notes

Reaction equation

HRID 2099731 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-4d3175d560ea411486b67eab06f076a6
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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