Sodium Methoxide → 1-Benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide

HRID 919857Notes

Reaction equation

HRID 919857 reaction equation
CO[C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([CH3:15])[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].Cl.[NH2:32][CH2:33][CH2:34][N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37].C[O-].[Na+]>CCO>[CH3:39][S:36]([N:35]([CH3:40])[CH2:34][CH2:33][NH:32][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([CH3:15])[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4])(=[O:38])=[O:37]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 54759137N-(2-aminoethyl)-N-methylmethanesulfonamide hydrochlorideHCID 682976491-Benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 867141351-Benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amideYield 34.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 1-benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (35 mg, 0.088 mmol), N-(2-amino-ethyl)-N-methyl-methanesulfonamide HCl salt (83 mg, 0.44 mmol), and NaOMe (24 mg, 0.44 mmol) in EtOH (3 mL) was heated at 140° C. for 6 h in a microwave reactor. Solvent was evaporated in vacuo, and the residue was partitioned between EtOAc and 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. The residue was purified twice by silica gel chromatography (first eluted with 0-2.5% MeOH/CH2Cl2, then with 15-100% EtOAc/hexanes+2% AcOH) to give 16 mg of the title compound as an off-white solid. MS: (+) m/z 521.28 (M+1).

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was partitioned between EtOAc and 0.1 M HCl
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified twice by silica gel chromatography (
  6. washfirst eluted with 0-2.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-f9fc937f78f1457c87d0700f05626951
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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