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 336889Notes

Reaction equation

HRID 336889 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](OCCCC)=[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 87883Butyl 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 15minutes, tent-Butyl bromoacetate (19 mL, 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-de7fd25c1b1b4bc4a208dbd2ca4bc8f4
Source dataset
uspto-grants-2014_11
Patent number
US08889706B2

Reaction notes

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