Potassium Carbonate → 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(2,2-dimethoxyethoxy)benzamide

HRID 620248Notes

Reaction equation

HRID 620248 reaction equation
Cl.[NH2:2][C:3]1[C:18]([Cl:19])=[CH:17][C:6]([C:7]([NH:9][CH2:10][CH2:11][N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[O:8])=[C:5]([OH:20])[CH:4]=1.[CH3:21][O:22][CH:23]([O:26][CH3:27])[CH2:24]Cl.C(=O)([O-])[O-].[K+].[K+].[Br-].[Na+]>CN(C=O)C>[NH2:2][C:3]1[C:18]([Cl:19])=[CH:17][C:6]([C:7]([NH:9][CH2:10][CH2:11][N:12]([CH2:13][CH3:14])[CH2:15][CH3:16])=[O:8])=[C:5]([O:20][CH2:24][CH:23]([O:26][CH3:27])[O:22][CH3:21])[CH:4]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 609862-Chloro-1,1-dimethoxyethaneHCID 253881Sodium BromideHCID 141168774-amino-5-chloro-N-(2-(diethylamino)ethyl)-2-hydroxybenzamide hydrochloride

Product 1

HCID 141169384-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(2,2-dimethoxyethoxy)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (8.06 g, 0.025 mole), chloroacetaldehyde dimethyl acetal (6.23 g; 0.05 mole), potassium carbonate (6.91 g, 0.05 mole) and sodium bromide (2.57 g, 0.025-mole) in 100 ml of dry DMF was stirred at reflux for 8 hours. After four hours at reflux an additional amount of the alkylating agent (6.23 g, 0.05 mole) was added. The mixture was filtered and the DMF was removed under vacuum. The oily residue was redissolved in methylene chloride and washed sequentially with water, aqueous 1.0N NaOH, water and saturated NaCl solution. The solvent was evaporated and the product was further purified by chromatography using a gradient elution of methanol-methylene chloride containing 0.25% of ammonia. The appropriate fractions were combined and evaporated to give a yellow residue. Recrystallization from ethyl acetate-petroleum ether yielded the title compound as a white solid; wt. 5.5 g (59.8%), mp 64°-67°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.32 (s, 1H); 4.83 (t, 2H); 4.42 (bs, 2H); 4.08 (d, 2H); 3.55 (m, 2H); 3.50 (m, 2H); 2.41 (m, 6H); 1.1 (t, 6H).

Workup

  1. temperatureat reflux for 8 hours
  2. temperatureAfter four hours at reflux an additional amount of the alkylating agent (6.23 g, 0.05 mole)
  3. additionwas added
  4. filtrationThe mixture was filtered
  5. customthe DMF was removed under vacuum
  6. dissolutionThe oily residue was redissolved in methylene chloride
  7. washwashed sequentially with water, aqueous 1.0N NaOH, water and saturated NaCl solution
  8. customThe solvent was evaporated
  9. customthe product was further purified by chromatography
  10. washa gradient elution of methanol-methylene chloride containing 0.25% of ammonia
  11. customevaporated
  12. customto give a yellow residue
  13. customRecrystallization from ethyl acetate-petroleum ether

Sources & evidence

ORD record
ord-0941591b4251408ca8a3fd38592f99aa
Source dataset
uspto-grants-1989_04
Patent number
US04820715

Reaction notes

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