Triethylamine → 7-(3,3-Dimethoxypyrrolidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

HRID 846688

反応式

HRID 846688 の反応式
[CH3:1][O:2][C:3]1([O:8][CH3:9])[CH2:7][CH2:6][NH:5][CH2:4]1.[F:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1F)[N:17]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[F:29])[CH:16]=[C:15]([C:30]([OH:32])=[O:31])[C:14]2=[O:33].C(N(CC)CC)C>>[CH3:1][O:2][C:3]1([O:8][CH3:9])[CH2:7][CH2:6][N:5]([C:20]2[CH:19]=[C:18]3[C:13]([C:14](=[O:33])[C:15]([C:30]([OH:32])=[O:31])=[CH:16][N:17]3[C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])=[CH:12][C:11]=2[F:10])[CH2:4]1

参加物

4

反応物 3

HCID 8471TriethylamineHCID 598041-(2,4-Difluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acidHCID 110298823,3-Dimethoxypyrrolidine

生成物 1

HCID 198832767-(3,3-Dimethoxypyrrolidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

反応条件

温度
45 °C

実験手順

Into an oven-dried glass flask flushed with dry N2, and containing 6 mL of dry pyridine were placed 0.116 g (0.88 mmol) of 3,3-dimethoxypyrrolidine, from Step 4, then 0.150 g (0.44 mmol) of 6,7-difluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (preparation described by H. Tone et al., Eur. Pat. Appl. EP 181521, May, 1986), and 180 mL (1.3 mmol) of triethylamine. This reaction solution was maintained under N2 and heated to 45° C. for 41 hours. The pyridine was then removed by azeotropic distillation with toluene, the residue triturated with water, the pH adjusted to pH 5 to 6 with acetic acid, and the solution filtered. The solid was washed with hot ethanol:water (3:1), which was refiltered and dried to afford the title compound, mp 228°-230° C.; MS(DCl) M/Z: 449 (M+H), 404 (M-COOH); NMR d 2.13 (dd, 2H, J=7.5 Hz), 3.41 (dd, 2H, J=1.5 Hz, J=7.5 Hz), 3.62 (d, 2H, J=3.6 Hz), 3.27 (s, 6H), 5.87 (d, 1H, J=7.5 Hz), 7.30 (m, 2H), 7.65 (m, 1H), 7.95 (d, 1H, J=13.5 Hz), 8.60 (s, 1H). Analysis calculated for C22H19F3N2O5 ·0.5 H2O: C, 59.77; H, 4.41; N, 6.12. Found: C, 58.28; H, 4.34; N, 6.21.

後処理

  1. customInto an oven-dried glass flask flushed with dry N2
  2. additioncontaining 6 mL of dry pyridine
  3. temperatureThis reaction solution was maintained under N2
  4. customThe pyridine was then removed by azeotropic distillation with toluene
  5. customthe residue triturated with water
  6. filtrationthe solution filtered
  7. washThe solid was washed with hot ethanol:water (3:1), which
  8. customdried

出典と根拠

ORDレコード
ord-4a78288dd33244bfaf28778dd51076b0
出典データセット
uspto-grants-1992_08
特許番号
US05137892

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