Ethyl bromoacetate → 5-Chloro-N-(5-chloropyridin-2-yl)-2-[(1-ethoxycarbonylmethylpiperidin-4-yl)methylamino]benzamide

HRID 988692Notes

Reaction equation

HRID 988692 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][CH2:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8].Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][CH2:19][CH:20]2[CH2:21][CH2:22][N:23]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:24][CH2:25]2)=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 98861065-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide

Product 1

HCID 219062585-Chloro-N-(5-chloropyridin-2-yl)-2-[(1-ethoxycarbonylmethylpiperidin-4-yl)methylamino]benzamideYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 5-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide from Example 60 (0.5 g, 1.32 mmol)in 30 mL of dimethylformamide was treated with excess ethyl bromoacetate (0.7 mL, 6.60 mmol). After heating at 70° C. for 1 h, triethylamine (0.9 ml, 6.6 mmol) was added dropwise; the reaction mixture was then heated at 70° C. for an additional 30 min, after which it was partitioned between saturated sodium bicarbonate and dichloromethane. The organic extract was concentrated in vacuo, and the residue was applied to a 10 g SCX column which was washed with methanol and eluted with 1 N ammonia in methanol. The yellow fractions were combined and concentrated in vacuo to afford an orange oil, which was subjected to silica gel chromatography. Elution with 9:1 dichloromethane-methanol, then 9:3 dichloromethane-methanol provided 0.31 g (51%) of the title compound as a yellow solid.

Workup

  1. temperaturethe reaction mixture was then heated at 70° C. for an additional 30 min
  2. customafter which it was partitioned between saturated sodium bicarbonate and dichloromethane
  3. extractionThe organic extract
  4. concentrationwas concentrated in vacuo
  5. washwas washed with methanol
  6. washeluted with 1 N ammonia in methanol
  7. concentrationconcentrated in vacuo
  8. customto afford an orange oil, which
  9. washElution with 9:1 dichloromethane-methanol

Sources & evidence

ORD record
ord-d57150c0fe004854ade7b5f6bae70c45
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

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