p-Toluenesulfonic acid → (R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one

HRID 1373375Notes

Reaction equation

HRID 1373375 reaction equation
C(OC(=O)[NH:7][C@@H:8]([C:12]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH:9]([CH3:11])[CH3:10])(C)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[NH2:7][C@@H:8]([C:12]1[N:21]([CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH:9]([CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 57351218(R)-tert-Butyl 1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropylcarbamate

Product 1

HCID 21015281(R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet, heating mantle and water condenser, is charged with 60 mL of toluene, 4.42 g (10 mmol) of (R)-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester (the compound of Formula 107 or 203 prepared, e.g., as described in Example 6.4 or 6.3), and 4.20 g of PTSA. The mixture is heated to reflux for 1 h, during which the evolution of gas is observed. Upon cessation of gas evolution, TLC analysis (hexanes/ethyl acetate 7:3) indicates complete reaction. The mixture is cooled to room temperature, initially forms an oil that separates at the bottom of the flask and quickly solidifies into a brown solid. Toluene is decanted and 50 mL of saturated potassium bicarbonate (room temperature) is added to the solid with stirring followed by the addition of 25 mL of water. The resulting white solid is collected by filtration to afford the title compound of Formula 301, (R)-2-(1-amino-2-methyl-propyl)-3-benzyl-7-chloro-3H-quinazolin-4-one.

Workup

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet
  2. temperatureheating mantle
  3. customprepared
  4. temperatureThe mixture is heated
  5. temperatureto reflux for 1 h, during which the evolution of gas
  6. customreaction
  7. customToluene is decanted
  8. addition50 mL of saturated potassium bicarbonate (room temperature) is added to the solid
  9. additionfollowed by the addition of 25 mL of water
  10. filtrationThe resulting white solid is collected by filtration

Sources & evidence

ORD record
ord-7e1464bca4eb432bb0e53ff70b87021e
Source dataset
uspto-grants-2007_01
Patent number
US07161002B2

Reaction notes

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