Toluene → 3-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-2-methyl-6-(trifluoromethyl)pyridine 1-oxide

HRID 2101335

반응식

HRID 2101335 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.O[CH2:25][C:26]1[C:27]([CH3:37])=[N+:28]([O-:36])[C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:17])[N:15]([CH2:25][C:26]4[C:27]([CH3:37])=[N+:28]([O-:36])[C:29]([C:32]([F:35])([F:33])[F:34])=[CH:30][CH:31]=4)[N:16]=[C:10]3[C:9]=2[C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:4][CH:3]=1

참가 물질

8

반응물 5

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 577993927-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneHCID 598348163-Pyridinemethanol, 2-methyl-6-(trifluoromethyl)-, 1-oxide

생성물 1

HCID 577993553-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-2-methyl-6-(trifluoromethyl)pyridine 1-oxide수율 69%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of 7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (64 mg, 0.2 mmol), 3-(hydroxymethyl)-2-methyl-6-(trifluoromethyl)pyridine 1-oxide (41 mg, 0.2 mmol) and Ph3P (105 mg, 0.4 mmol) in anhydrous THF (3 mL) at room temperature was added dropwise a 40% solution of DEAD in toluene (0.091 mL, 0.4 mmol). The resulting clear, yellowish solution was then stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3, then saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluted with a gradient of ethyl acetate (40-100%) in hexanes to afford 70 mg (69%) of the title compound as a light yellow foam. A portion of the product (10 mg) was further purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 40% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 7.2 mg of the title compound as a light yellow powder. HPLC/MS: retention time=2.33 min, [M+H]+=512.0.

후처리

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialsaturated aqueous NaCl, dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified
  6. washeluted with a gradient of ethyl acetate (40-100%) in hexanes

출처 및 근거

ORD 기록
ord-c82b34634b424ae5afd1b1f2a0b6a9d6
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572808B2

연결된 노트

불러오는 중…