Potassium Carbonate → 4-[1-(2-Methyl-8-nitro-1-oxo-1,2,3,4-tetrahydro-isoquinolin-5-yl)-piperidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 604277Notes

Reaction equation

HRID 604277 reaction equation
F[C:2]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH3:16])[C:7]2=[O:15].[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[C:17]([O:21][C:22]([N:24]1[CH2:25][CH2:26][N:27]([CH:30]2[CH2:35][CH2:34][N:33]([C:2]3[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]4[C:3]=3[CH2:4][CH2:5][N:6]([CH3:16])[C:7]4=[O:15])[CH2:32][CH2:31]2)[CH2:28][CH2:29]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 17750356tert-Butyl 4-(piperidin-4-yl)piperazine-1-carboxylateHCID 598491765-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 598491704-[1-(2-Methyl-8-nitro-1-oxo-1,2,3,4-tetrahydro-isoquinolin-5-yl)-piperidin-4-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one (11.65 g, 0.052 mol), 4-piperidin-4-yl-piperazine-1-carboxylic acid tert-butyl ester (28.0 g, 0.1039 mol), K2CO3 (8.98 g, 0.065 mol) in DMSO (350 mL) was stirred at 85° C. for 12 hours. After cooling to room temperature, ice-water (500 mL) was added. The mixture was extracted with AcOEt. The organic layer was washed with water followed by brine, dried over Na2SO4 and evaporated. The residue was purified by silica gel column chromatography (AcOEt; then AcOEt/MeOH=6/1) to give 10.09 g of the desired product 4-[1-(2-methyl-8-nitro-1-oxo-1,2,3,4-tetrahydro-isoquinolin-5-yl)-piperidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester as pale yellow solid in 41% yield.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with AcOEt
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography (AcOEt

Sources & evidence

ORD record
ord-ebeaa36887304526a75545382def6811
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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