Triphosgene → 3-(1-Benzylpiperidin-4-yl)-8-fluoroquinazoline-2,4(1H,3H)-dione

HRID 1353628Notes

Reaction equation

HRID 1353628 reaction equation
[NH2:1][C:2]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)=[O:5].Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH2:13]([N:10]1[CH2:11][CH2:12][CH:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[C:23]([F:24])[CH:22]=[CH:21][CH:20]=3)[NH:1][C:26]2=[O:28])[CH2:8][CH2:9]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 211021192-Amino-N-(1-benzylpiperidin-4-yl)-3-fluorobenzamide

Product 1

HCID 211021553-(1-Benzylpiperidin-4-yl)-8-fluoroquinazoline-2,4(1H,3H)-dioneYield 258.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-amino-N-(1-benzylpiperidin-4-yl)-3-fluorobenzamide (750 mg, 2.29 mmol) in dichloromethane (30.0 mL) at 0° C. was added triphosgene (227 mg, 0.33 equiv.) as a solution in dichloromethane (5 mL). The ice bath was removed and the reaction heated at reflux for 6 h. The reaction was concentrated, dissolved in ethyl acetate, washed with saturated sodium bicarbonate, then water, then brine, dried over magnesium sulfate, and concentrated to give 700 mg of a white solid. The crude product was purified by flash chromatography to give 205 mg (25%) as a white solid. Mass spec.: 354.13 (MH)+.

Workup

  1. customThe ice bath was removed
  2. temperaturethe reaction heated
  3. temperatureat reflux for 6 h
  4. concentrationThe reaction was concentrated
  5. dissolutiondissolved in ethyl acetate
  6. washwashed with saturated sodium bicarbonate
  7. dry with materialwater, then brine, dried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e1c871450fc142e88b920cdcb1fd3179
Source dataset
uspto-grants-2007_05
Patent number
US07220862B2

Reaction notes

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