Potassium Hydroxide → 6-Chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine

HRID 1502301ノート

反応式

HRID 1502301 の反応式
[NH2:1][C:2]1[C:3]([CH:9](O)[CH3:10])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[F:12][C:13]1[CH:14]=[CH:15][C:16]([CH3:22])=[C:17]([C:19](=O)[CH3:20])[CH:18]=1.[OH-].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Ru]Cl>[Cl:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][N:6]=1)[N:1]=[C:19]([C:17]1[CH:18]=[C:13]([F:12])[CH:14]=[CH:15][C:16]=1[CH3:22])[CH:20]=[C:9]2[CH3:10]

参加物

6

反応物 4

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 153354201-(5-Fluoro-2-methylphenyl)ethan-1-oneHCID 866749441-(5-Amino-2-chloropyridin-4-yl)ethanol

生成物 1

HCID 866749456-Chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine収率 36.3%

試薬・触媒・溶媒 1

HCID 11007548Dichlorotris(triphenylphosphine)ruthenium触媒

反応条件

温度
80 °C

実験手順

A screw-top vial was charged with 1-(5-amino-2-chloropyridin-4-yl)ethanol (46.3 mg, 0.268 mmol), 5′-fluoro-2′-methylacetophenone (82.0 mg, 0.540 mmol), tris(triphenylphosphine)ruthenium(II) dichloride (13.0 mg, 0.013 mmol), potassium hydroxide (15 mg, 0.27 mmol), and 1,4-dioxane (1.5 mL, 19 mmol). The reaction vial was flushed with nitrogen gas, sealed with a teflon lined cap, and heated at 80° C. for 2 hours. The reaction mixture was then diluted in ethyl acetate, filtered through celite, washed with water and brine, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-100% ethyl acetate in heptane) to yield 27.9 mg (36%) of 6-chloro-2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridine. LCMS (ESI): M+H=287.2; 1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.20 (s, 1H), 7.91 (s, 1H), 7.41 (m, 2H), 7.26 (m, 1H), 2.75 (s, 3H), 2.37 (s, 3H).

後処理

  1. customThe reaction
  2. customvial was flushed with nitrogen gas
  3. customsealed with a teflon
  4. customlined cap
  5. additionThe reaction mixture was then diluted in ethyl acetate
  6. filtrationfiltered through celite
  7. washwashed with water and brine
  8. dry with materialdried over MgSO4
  9. customevaporated in vacuo
  10. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-100% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-0068cc6e31be480c9707492a7295462a
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

反応ノート

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