Potassium Carbonate → N-(4-Methoxybenzyl)-N,7-dimethyl-5-{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazin-4-amine

HRID 1907201

반응식

HRID 1907201 반응식
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]([CH3:25])[C:9]2[C:14]3=[C:15]([C:19]4[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=4)[N:16]=[C:17]([CH3:18])[N:13]3[N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.Br[C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([CH3:25])[C:9]2[C:14]3=[C:15]([C:19]4[CH:20]=[N:21][N:22]([CH3:24])[C:23]=4[C:29]4[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][N:30]=4)[N:16]=[C:17]([CH3:18])[N:13]3[N:12]=[CH:11][N:10]=2)=[CH:26][CH:27]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 68182074N-(4-methoxybenzyl)-N,7-dimethyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazin-4-amine

생성물 1

HCID 68182068N-(4-Methoxybenzyl)-N,7-dimethyl-5-{1-methyl-5-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazin-4-amine수율 56.1%

시약·촉매·용매 2

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-촉매HCID 312751,4-Dioxane용매

반응 조건

온도
160 °C

실험 절차

N-(4-Methoxybenzyl)-N,7-dimethyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazin-4-amine (10.0 g, 27.5 mmol), 2-bromo-5-(trifluoromethyl)pyridine (12.4 g, 54.9 mmol) and powdered potassium carbonate (11.4 g, 82.5 mmol) were combined in 1,4-dioxane (90 mL) and heated at reflux for 10 minutes. Allylpalladium chloride dimer (98%, 514 mg, 1.38 mmol) was added, and the reaction was heated for 22 hours at 160° C. in a sealed tube capped with a Q-Tube™ (Q Labtech). The reaction was cooled to room temperature and concentrated in vacuo. The residue was suspended in ethyl acetate, filtered through Celite and concentrated under reduced pressure. Silica gel chromatography (Gradient: 50% to 100% ethyl acetate in heptane) provided a pale brown foam (7.85 g), which was crystallized from heptane (˜100 mL) and ethyl acetate (˜5 mL) to provide the product as a pale brown powder. Yield: 7.00 g, 13.8 mmol, 50%. LCMS m/z 509.1 (M+1). 1H NMR (500 MHz, CDCl3) δ 2.54 (s, 3H), 2.72 (s, 3H), 3.75 (s, 3H), 4.14 (s, 3H), 4.34 (br s, 2H), 6.76 (br d, J=8.8 Hz, 2H), 6.94 (br d, J=8.5 Hz, 2H), 7.39 (d, J=8.3 Hz, 1H), 7.72 (s, 1H), 7.76 (dd, J=8.3, 2.2 Hz, 1H), 7.85 (s, 1H), 8.95-8.96 (m, 1H).

후처리

  1. temperatureheated
  2. temperatureat reflux for 10 minutes
  3. customcapped with a Q-Tube™ (Q Labtech)
  4. temperatureThe reaction was cooled to room temperature
  5. concentrationconcentrated in vacuo
  6. filtrationfiltered through Celite
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-44014dfff1e047a5a51bfc5375760f50
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598155B2

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