Diphenyl Ether → 4-Amino-2-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-6(7H)-one

HRID 573561ノート

反応式

HRID 573561 の反応式
[NH2:1][C:2]1[C:3]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=3)=[C:14]([CH3:24])[S:13][C:4]=2[NH:5][C:6](=[O:12])[C:7]=1C(OC)=O.[OH-].[Na+].C1(OC2C=CC=CC=2)C=CC=CC=1>C(O)C>[NH2:1][C:2]1[C:3]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=3)=[C:14]([CH3:24])[S:13][C:4]=2[NH:5][C:6](=[O:12])[CH:7]=1

参加物

5

反応物 3

HCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68323874Methyl 4-amino-2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylate

生成物 1

HCID 683240244-Amino-2-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-6(7H)-one収率 43.7%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

To a stirred suspension of methyl 4-amino-2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (Description 35) (1.617 g, 4.70 mmol) in ethanol (20 mL) was added aqueous NaOH (5M) (4.70 mL, 23.48 mmol). The suspension was then refluxed under nitrogen for ca. 2 h. The reaction mixture was then cooled to RT and concentrated in vacuo. The residue was partitioned between DCM and water (ca. 50 mL each) and acidified to ca. pH 7 using aqueous HCl (5M). The aqueous layer was separated and re-extracted with DCM (ca. 50 mL×2) and the combined organic layer passed through a phase separator and concentrated in vacuo. The residue was dissolved in diphenyl ether (20 mL, 126 mmol) and heated to 200° C. under nitrogen atmosphere for ca. 2 h. The mixture was then cooled to RT, passed through SCX cartridge (eluting with MeOH followed by 2M NH3 MeOH) and the basic fractions combined and concentrated in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-20% MeOH in DCM, to afford the title compound (588 mg). LCMS (A) m/z: 285 [M−1]−, Rt 1.10 min (acidic).

後処理

  1. temperatureThe suspension was then refluxed under nitrogen for ca. 2 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between DCM and water (ca. 50 mL each)
  4. customThe aqueous layer was separated
  5. extractionre-extracted with DCM (ca. 50 mL×2)
  6. concentrationconcentrated in vacuo
  7. temperatureheated to 200° C. under nitrogen atmosphere for ca. 2 h
  8. temperatureThe mixture was then cooled to RT
  9. washpassed through SCX cartridge (eluting with MeOH followed by 2M NH3 MeOH)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by normal phase chromatography
  12. washeluting with a gradient of 0-20% MeOH in DCM

出典と根拠

ORDレコード
ord-da2db0208f0841d89b74fad142d682aa
出典データセット
uspto-grants-2015_05
特許番号
US09029545B2

反応ノート

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