Hydrochloric Acid → HCID 178470118、化合物

HRID 1640942ノート

反応式

HRID 1640942 の反応式
S.[Na].[CH2:3]([O:5][C:6]([C:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Br:20])=[C:14]([F:19])[CH:15]=2)[N:10]([CH:21]2[CH2:23][CH2:22]2)[C:9]=1[S:24]C)=[O:7])[CH3:4].Cl>C1COCC1.O.CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Br:20])=[C:14]([F:19])[CH:15]=2)[N:10]([CH:21]2[CH2:22][CH2:23]2)[C:9]=1[SH:24])=[O:7])[CH3:4]

参加物

7

反応物 3

HCID 313Hydrochloric AcidHCID 599995377-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl esterHCID 86586439Sodium hydrogen sulphide2 回

生成物 1

HCID 178470118HCID 178470118、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
45 °C

実験手順

Sodium hydrogen sulfide (5 mg, 0.09 mmole, 1.5 equiv.) is added to a stirred solution of 7-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (5, 24 mg, 0.06 mmole) in THF (tetrahydrofuran, 2 ml) under argon at room temperature. The reaction is then stirred at 45° C. until TLC indicated completion. The reaction mixture is diluted with water and washed with diethyl ether. The aqueous layer is acidified by 1N HCl to a pH of approximately 2, and extracted with EtOAc. The resulting organics are washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product is purified by PTLC (20% CH3OH in CHCl3) to give 6. Alternatively, sodium hydrogen sulfide (20 mg, 0.36 mmole, 1.5 equiv.) is added to a stirred solution of 5 (crude, 96 mg, 0.24 mmole) in DMF (6 ml) under argon at room temperature. The reaction is then stirred at 40° C. until TLC indicates completion. The reaction mixture is diluted with water, acidified by 1N HCl to a pH of approximately 2, and extracted with EtOAc. The resulting organics are washed with brine, dried over Na2SO4, and concentrated. The crude is purified by PTLC (20% CH3OH in CHCl3) to yield 6. 1H NMR (CDCl3) δ: 8.40 (d, 1H), 8.06 (d, 1H), 4.71 (q, 2H), 3.46 (m, 1H), 1.68 (m, 7H).

後処理

  1. washwashed with diethyl ether
  2. extractionextracted with EtOAc
  3. washThe resulting organics are washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by PTLC (20% CH3OH in CHCl3)
  7. customto give 6
  8. stirringThe reaction is then stirred at 40° C. until TLC
  9. extractionextracted with EtOAc
  10. washThe resulting organics are washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customThe crude is purified by PTLC (20% CH3OH in CHCl3)
  14. customto yield 6

出典と根拠

ORDレコード
ord-18c45434015841719ec4e8a5423ec966
出典データセット
uspto-grants-2012_02
特許番号
US08114888B2

反応ノート

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