Formaldehyde → 1,8-Naphthyridine-3-carboxylic acid, 1,4-dihydro-6-fluoro-1-(2-fluoroethyl)-7-(4-methyl-1-piperazinyl)-4-oxo-

HRID 2413119Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[N:8]([CH2:18][CH2:19][F:20])[CH:7]=[C:6]([C:21]([OH:23])=[O:22])[C:5]2=[O:24].[CH2:25]=O>C(O)=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([CH3:25])[CH2:14][CH2:13]1)[N:8]([CH2:18][CH2:19][F:20])[CH:7]=[C:6]([C:21]([OH:23])=[O:22])[C:5]2=[O:24]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylic acid (3.0 g), 37% formalin (4 ml) and formic acid (9 ml) is heated at 110° C. for 16 hours with stirring. The reaction mixture is concentrated to dryness under reduced pressure. The residue is dissolved in 10% aqueous ammonia, treated with active charcoal, and filtered. The filtrate is adjusted to pH 8-8.5 with 10% hydrochloric acid. The precipitate is collected by filtration, and recrystallized from acetonitrile to give 2.67 g of 6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid (compound 1), m.p. 224°-226° C.

Workup

concentrationThe reaction mixture is concentrated to dryness under reduced pressure
dissolutionThe residue is dissolved in 10% aqueous ammonia
additiontreated with active charcoal
filtrationfiltered
filtrationThe precipitate is collected by filtration
customrecrystallized from acetonitrile

Sources & evidence

ORD record: ord-7c7a2e0a8d0f4f959a00df93c865f640
Source dataset: uspto-grants-1985_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04496566

Reaction notes

Loading…