Triethylamine → (R)-7-[3-(1-Amino-1-methylethyl)-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic Acid

HRID 1197995Notes

Reaction equation

HRID 1197995 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([CH3:21])[C:15]([F:20])=[C:16](F)[CH:17]=2)[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1.C([N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])C>C(#N)C>[NH2:9][C:3]([C@@H:32]1[CH2:30][CH2:29][N:28]([C:16]2[CH:17]=[C:18]3[C:13]([C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10][N:9]3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[C:14]([CH3:21])[C:15]=2[F:20])[CH2:31]1)([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 14651285HCID 14651285, compound

Product 1

HCID 15230565(R)-7-[3-(1-Amino-1-methylethyl)-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic AcidYield 244.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 0.92 g (2.62 mmol) of 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid, 0.90 g (3.9 mmol) of (3R)-(1,-methyl-1'-t-butoxycarbonylaminoethyl)pyrrolidine (9a), 0.80 g (7.9 mmol) of triethylamine, and 50 mL of acetonitrile was heated at reflux for 18 hours. The solution was cooled to room temperature and concentrated in vacuo to an orange solid. The residue was chromatographed on E. Merck silica gel (230-400 mesh), eluting with 90:10 CHCl3:MeOH to give 1.47 g of (R) 7-[3-(1-t-butoxycarbonylamino-1-methylethyl)-1-pyrrolidinyl]-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid; NMR (CDCl3) δ8.47 (s, 1 H), 7.44 (m, 1 H), 7.15 (m, 2 H), 5.64 (d, J=7 HZ, 1 H), 4.47 (bs, 1 H), 3.50- 3.20 (m, 4 H), 2.85 (d, J=3.5 HZ, 3 H), 1.91 (m, 1 H), 1.74 (m, 2 H), 1.42 (s, 9 H), 1.29 (d, J=11 HZ, 6 H).

Workup

  1. temperatureat reflux for 18 hours
  2. concentrationconcentrated in vacuo to an orange solid
  3. customThe residue was chromatographed on E
  4. washMerck silica gel (230-400 mesh), eluting with 90:10 CHCl3

Sources & evidence

ORD record
ord-b79bb664d99f4e40a4f2e6f1d9846586
Source dataset
uspto-grants-1994_01
Patent number
US05278317

Reaction notes

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