Triethylamine → 7-(5-Acetamidomethyl-2-isoindolinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester

HRID 1494821Notes

Reaction equation

HRID 1494821 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11](Cl)=[C:12]([F:17])[CH:13]=2)[N:8]([CH:19]2[CH2:21][CH2:20]2)[CH:7]=1)=[O:5])[CH3:2].[C:22]([NH:25][CH2:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[CH2:32][NH:31][CH2:30]2)(=[O:24])[CH3:23].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([N:31]3[CH2:30][C:29]4[C:33](=[CH:34][CH:35]=[C:27]([CH2:26][NH:25][C:22](=[O:24])[CH3:23])[CH:28]=4)[CH2:32]3)=[C:12]([F:17])[CH:13]=2)[N:8]([CH:19]2[CH2:21][CH2:20]2)[CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11722954Ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateHCID 15167905N-(isoindolin-5-ylmethyl)acetamide

Product 1

HCID 572711897-(5-Acetamidomethyl-2-isoindolinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl esterYield 56.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A mixture of 310 mg of 1-cyclopropyl-6-fluoro-7- chloro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester, 745 mg of 5-acetamidomethylisoindoline, 0.56 ml of triethylamine, and 5 ml of anhydrous chloroform was heated at 60°-70° C. for 0.5 hours while stirring. The resulting reaction mixture was diluted with 25 ml of chloroform. The mixture was washed with 5% acetic acid and brine in this order, dried over anhydrous sodium sulfate, and condensed. The residue was crystallized by the addition of ethylether. The crystals were collected by filtration and recrystallized from a mixed solvent of chloroform, methanol, and ethanol to obtain 260 mg of 7-(5- acetamidomethyl-2-isoindolinyl)-1-cyclopropyl-6-fluoro-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester.

Workup

  1. temperaturewas heated at 60°-70° C. for 0.5 hours
  2. customThe resulting reaction mixture
  3. washThe mixture was washed with 5% acetic acid and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate, and condensed
  5. customThe residue was crystallized by the addition of ethylether
  6. filtrationThe crystals were collected by filtration
  7. customrecrystallized from a mixed solvent of chloroform, methanol, and ethanol

Sources & evidence

ORD record
ord-2d267b3f4c654f349eb5968f795189ac
Source dataset
uspto-grants-1991_06
Patent number
US05026856

Reaction notes

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