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

HRID 1502301노트

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HRID 1502301 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 11007548Dichlorotris(triphenylphosphine)ruthenium촉매

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온도
80 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0068cc6e31be480c9707492a7295462a
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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