Reacción #604425

Ecuación de reacción

lithium diisopropylamide

4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile

4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile

lithium diisopropylamide

1-(3-bromopropyl)pyrrolidine hydrobromide

Water

→

4-(1-(3-(Trifluoromethyl)phenyl)-2,5-dioxo-3-(3-(pyrrolidin-1-yl)propyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

Disolventes

N,N-dimethyl-formamide

solution A

N,N-dimethyl-formamide

solution A

N,N-dimethyl-formamide

N,N-dimethylformamide

solution B

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónthe mixture is extracted twice with dichloromethane
2. 2
   SecadoThe combined organic layers are dried over Na2SO4
3. 3
   Concentraciónconcentrated under reduced pressure
4. 4
   OtroThe residue is purified by reversed phase HPLC (Waters Xbridge-C18, gradient of methanol in water, 0.1% TFA)
5. 5
   Otro1.15 min (V001—006)

Procedimiento

In a first flask, lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added at 0° C. to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 100 mg, 0.243 mmol) in N,N-dimethyl-formamide (3 mL, solution A). In another flask, lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added to a solution of 1-(3-bromopropyl)pyrrolidine hydrobromide (70 mg, 0.256 mmol) in N,N-dimethylformamide (2 mL, solution B). This solution is then added to solution A and the resulting mixture is stirred at room temperature over night. Water is added, and the mixture is extracted twice with dichloromethane. The combined organic layers are dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Waters Xbridge-C18, gradient of methanol in water, 0.1% TFA). Yield: 15 mg; ESI mass spectrum [M+H]+=523; Retention time HPLC: 1.15 min (V001—006).

Fuente