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

HRID 517243Notes

Reaction equation

HRID 517243 reaction equation
C([N-]C(C)C)(C)C.[Li+].[O:9]=[C:10]1[NH:19][CH:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)[C:17]2[C:16](=[O:28])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1.Br.Br[CH2:41][CH2:42][CH2:43][N:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1.O>CN(C)C=O>[F:37][C:35]([F:38])([F:36])[C:31]1[CH:30]=[C:29]([N:11]2[C:12]3[CH2:13][CH2:14][CH2:15][C:16](=[O:28])[C:17]=3[CH:18]([C:20]3[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=3)[N:19]([CH2:41][CH2:42][CH2:43][N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)[C:10]2=[O:9])[CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2724682Lithium diisopropylamide2×HCID 201359201-(3-Bromopropyl)pyrrolidine hydrobromideHCID 86732326HCID 86732326, compound

Product 1

HCID 867323644-(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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent5×

Procedure

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).

Workup

  1. extractionthe mixture is extracted twice with dichloromethane
  2. dry with materialThe combined organic layers are dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by reversed phase HPLC (Waters Xbridge-C18, gradient of methanol in water, 0.1% TFA)
  5. custom1.15 min (V001—006)

Sources & evidence

ORD record
ord-3b7452923c1a4a9088a1419ae0b44f6b
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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