1-Methylpiperidine-4-methylamine → Ethyl 6-bromo-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047137Notes

Reaction equation

HRID 1047137 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](F)=[C:6]([CH:19]=1)[C:7]([C:9](=[CH:15][N:16]([CH3:18])C)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:8].[CH3:21][N:22]1[CH2:27][CH2:26][CH:25](CN)[CH2:24][CH2:23]1>C1COCC1>[Br:1][C:2]1[CH:19]=[C:6]2[C:5](=[N:4][CH:3]=1)[N:16]([CH2:18][CH:25]1[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]1)[CH:15]=[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:7]2=[O:8]

Participants

4

Reactant 2

HCID 815741-Methylpiperidine-4-methylamineHCID 68749333Ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate2×

Product 1

HCID 68752677Ethyl 6-bromo-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 102%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate (Intermediate 3, 784 mg, 2.27 mmol) dissolved in THF (12 mL) was added (1-methylpiperidin-4-yl)methanamine (291 mg, 2.27 mmol). The reaction mixture was stirred at 60° C. for 2 h, then cooled to room temperature, concentrated under reduced pressure, and the resulting residue was resuspended in DMF (12 mL). Potassium carbonate was added (942 mg, 6.81 mmol, 3 equiv.) to the suspension, and the reaction was stirred at 70° C. for 18 h. The reaction mixture was cooled to room temperature then quenched with 1 N HCl. The reaction mixture was partitioned between water (15 mL) and dichloromethane (15 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×15 mL), and the combined organic layers were concentrated to provide ethyl 6-bromo-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (945 mg, >99%).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionPotassium carbonate was added (942 mg, 6.81 mmol, 3 equiv.) to the suspension
  4. stirringthe reaction was stirred at 70° C. for 18 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customthen quenched with 1 N HCl
  7. customThe reaction mixture was partitioned between water (15 mL) and dichloromethane (15 mL)
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
  10. concentrationthe combined organic layers were concentrated

Sources & evidence

ORD record
ord-0abc19635fcd4a57a143b624a18e7605
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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