Dichloromethane → 1,6-Dihydro-1-[2-(6-chloro-3-pyridinylcarbonylamino)ethyl]-6-oxo-3-pyridinecarboxylic acid methyl ester

HRID 2379083Notes

Reaction equation

HRID 2379083 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[N:7]([CH2:12][CH2:13][NH2:14])[CH:6]=1)=[O:4].[Cl:15][C:16]1[N:21]=[CH:20][C:19]([C:22](O)=[O:23])=[CH:18][CH:17]=1.ClCCl.C(N(CC)CC)C>C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[N:7]([CH2:12][CH2:13][NH:14][C:22]([C:19]2[CH:20]=[N:21][C:16]([Cl:15])=[CH:17][CH:18]=2)=[O:23])[CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 792226-Chloronicotinic acidHCID 54083902Methyl 1-(2-aminoethyl)-6-oxo-1,6-dihydropyridine-3-carboxylate

Product 1

HCID 543131641,6-Dihydro-1-[2-(6-chloro-3-pyridinylcarbonylamino)ethyl]-6-oxo-3-pyridinecarboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-8 °C

Procedure

To a 1 00 ml round bottomed flask fitted with a magnetic stirrer bar and nitrogen inlet was added the above amine (0.300 g, 1.53 mmol), 6-chloro-3-pyridinecarboxylic acid (0.241 g, 1.53 mmol), and dry dichloromethane 125.5 mmol). Upon cooling in a -8° C. ice bath with stirring, triethyl amine (1.07 ml, 7.65 mmol) and propylphosphonic acid anhydride (0.50 ml, added as a 0.50 ml ethyl acetate solution, Angew. Chemie 1980, 92(2), 129) were added. The flask was allowed to warm slowly to room temperature over 1.25 hours. Stirring was continued 30 minutes at which time the reaction mixture solution was washed with aqueous sodium bicarbonate (2X), brine, and dried (Na2SO4). Filtration, concentration and purification via medium pressure liquid chromotography (silica gel, 4% methanol/dichloromethane) have the desired product, MP: 188°-190° C.

Workup

  1. customTo a 1 00 ml round bottomed flask fitted with a magnetic stirrer bar and nitrogen inlet
  2. additionChemie 1980, 92(2), 129) were added
  3. temperatureto warm slowly to room temperature over 1.25 hours
  4. stirringStirring
  5. washthe reaction mixture solution was washed with aqueous sodium bicarbonate (2X), brine
  6. dry with materialdried (Na2SO4)
  7. filtrationFiltration, concentration and purification via medium pressure liquid chromotography (silica gel, 4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-97581b149c074b2ba518256dc6b2ef9d
Source dataset
uspto-grants-1994_11
Patent number
US05360808

Reaction notes

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