Sodium hydride → methyl 1-(4-(9-bromo-3-oxo-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate

HRID 1944612Notes

Reaction equation

HRID 1944612 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][CH:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:21][CH2:20]3)=[C:15]([C:29]([F:32])([F:31])[F:30])[CH:14]=1)=[CH:9][C:8]([Br:33])=[CH:7][CH:6]=2.[H-].[Na+].Br[CH2:37][C:38](OC(C)(C)C)=[O:39]>CN(C=O)C>[Br:33][C:8]1[CH:7]=[CH:6][C:5]2[N:4]=[CH:3][C:2]3[NH:1][C:38](=[O:39])[CH2:37][N:12]([C:13]4[CH:18]=[CH:17][C:16]([N:19]5[CH2:20][CH2:21][CH:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:23][CH2:24]5)=[C:15]([C:29]([F:31])([F:30])[F:32])[CH:14]=4)[C:11]=3[C:10]=2[CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 67008348HCID 67008348, compound

Product 1

HCID 67008030methyl 1-(4-(9-bromo-3-oxo-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylateYield 94.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 8.3 methyl 1-(4-(3-amino-6-bromoquinolin-4-ylamino)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (60 mg, 0.115 mmol, 1 equiv.) in anhydrous DMF (3 mL) at 0° C. was added sodium hydride (60%, 5.0 mg, 0.126 mmol, 1.1 equiv.). After the mixture solution was stirred for 15 minutes, tert-Butyl bromoacetate (19 ┌L, 0.126 mmol, 1.1 equiv.) was added. The resulting mixture was stirred overnight at room temperature under argon. Upon quenching with water, the mixture was concentrated under vacuum, diluted with EtOAc (20 mL), and washed with water (20 mL) and brine (20 mL). The organic phase was dried over Na2SO4. After removal of solvent under vacuum, the resulting residue was purified via flash chromatography (CH2Cl2:MeOH=35:1) to afford the desired product 8.4 methyl 1-(4-(9-bromo-3-oxo-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)piperidine-4-carboxylate (61 mg; 94%). LC-MS (M+H): 563.15

Workup

  1. stirringThe resulting mixture was stirred overnight at room temperature under argon
  2. customUpon quenching with water
  3. concentrationthe mixture was concentrated under vacuum
  4. additiondiluted with EtOAc (20 mL)
  5. washwashed with water (20 mL) and brine (20 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customAfter removal of solvent under vacuum
  8. customthe resulting residue was purified via flash chromatography (CH2Cl2:MeOH=35:1)

Sources & evidence

ORD record
ord-1aee18a8a60a4598968a2722a0944496
Source dataset
uspto-grants-2013_03
Patent number
US08394818B2

Reaction notes

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