Triethylamine → 7-[4-(t-Butoxycarbonylaminomethyl)-2-isoindolinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester

HRID 1494820Notes

Reaction equation

HRID 1494820 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]([O:26][C:27]([NH:29][CH2:30][C:31]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][NH:34][CH2:35]2)=[O:28])([CH3:25])([CH3:24])[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:34]3[CH2:33][C:32]4[C:36](=[CH:37][CH:38]=[CH:39][C:31]=4[CH2:30][NH:29][C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:35]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 198284894-(t-Butyloxycarbonylaminomethyl)isoindoline

Product 1

HCID 538742897-[4-(t-Butoxycarbonylaminomethyl)-2-isoindolinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl esterYield 80%

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, 524 mg of 4-(t-butyloxycarbonylaminomethyl)isoindoline, 0.42 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 417 mg of 7-[4- (t-butoxycarbonylaminomethyl)-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-c76fbd78718342b69aa0fa87ef5f1fe5
Source dataset
uspto-grants-1991_06
Patent number
US05026856

Reaction notes

Loading…