Dimethylformamide → tert-Butyl{1-[2-(7-chloro-2-oxo-1,8-naphthyridin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 255304Notes

Reaction equation

HRID 255304 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.CN(C=O)C.[H-].[Na+].CS(O[CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28]1)(=O)=O>O>[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[N:9]2[CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][CH:30]([NH:33][C:34](=[O:35])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:29][CH2:28]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 133023227-Chloro-1,8-naphthyridin-2-olHCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate3×

Product 1

HCID 86642642tert-Butyl{1-[2-(7-chloro-2-oxo-1,8-naphthyridin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 58%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 7-chloro-1,8-naphthyridin-2(1H)-one [J. Org. Chem. 1990, 55, 4744-4750] in dry DMF (20 mL) (540 mg, 3.0 mmol) at 0° C. was treated with sodium hydride (144 mg, 60% in mineral oil, 3.6 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction was cooled using an ice bath. A solution of 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1yl}ethyl methanesulfonate in DMF (Intermediate 6), 0.33 mmol/mL, 10 mL, 3.3 mmol) was then added over 1 hour. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was diluted with water and extracted with dichloromethane (3×50 mL). The combined organic layers were washed with saturated sodium chloride solution (3×10 mL), dried over sodium sulfate and evaporated. Chromatography on silica gel using methanol in dichloromethane (0-15%) gave the title compound as a brown foam (711 mg, 58%).

Workup

  1. temperatureThe reaction was cooled
  2. temperatureto warm to room temperature
  3. stirringstirred overnight
  4. extractionextracted with dichloromethane (3×50 mL)
  5. washThe combined organic layers were washed with saturated sodium chloride solution (3×10 mL)
  6. dry with materialdried over sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-a08c5c76fb384591824c0a297ddff960
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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