Methane → 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 1498036

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HRID 1498036 반응식
COC1C=CC([CH2:7][N:8](C)[C:9]2[C:14]3=[C:15]([C:19]4[CH:20]=[N:21][N:22]([CH3:34])[C:23]=4[C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=4)[N:16]=[C:17]([CH3:18])[N:13]3[N:12]=[CH:11][N:10]=2)=CC=1.FC(F)(F)C(O)=O.COC1C=CC=CC=1.C>ClCCl.CO>[CH3:7][NH:8][C:9]1[C:14]2=[C:15]([C:19]3[CH:20]=[N:21][N:22]([CH3:34])[C:23]=3[C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=3)[N:16]=[C:17]([CH3:18])[N:13]2[N:12]=[CH:11][N:10]=1

참가 물질

7

반응물 4

HCID 297MethaneHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 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-amine

생성물 1

HCID 60163376N,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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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온도
40 °C

실험 절차

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 (7.00 g, 13.8 mmol) was dissolved in dichloromethane (46 mL) and treated with trifluoroacetic acid (40 mL, 520 mmol) and methoxybenzene (99.7%, 7.0 mL, 64 mmol). The reaction mixture was heated at 40° C. for 4 hours, then concentrated in vacuo. Aqueous 1 N sodium hydroxide solution was added, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to provide crude product (12 g), which was combined with the crude product from two additional runs of this reaction (total starting material: 18.09 g, 35.57 mmol). The combined material was dissolved in hot methanol, allowed to cool slightly, and treated with Darco® activated carbon (8 g); this mixture was heated for 1 hour at 50° C. and filtered through Celite. The volume of the filtrate was reduced, and the solution was left to crystallize for 18 hours. The resulting beige crystals were determined by 1H NMR to contain residual methoxybenzene. Trituration with diethyl ether provided the product as a white solid. Combined yield: 8.73 g, 22.5 mmol, 63%. LCMS m/z 389.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.58 (s, 3H), 2.85 (s, 3H), 4.15 (s, 3H), 7.38 (br d, J=8.3 Hz, 1H), 7.73 (s, 1H), 7.85 (s, 1H), 7.98-8.01 (m, 1H), 9.02-9.04 (m, 1H).

후처리

  1. concentrationconcentrated in vacuo
  2. additionAqueous 1 N sodium hydroxide solution was added
  3. extractionthe mixture was extracted with ethyl acetate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customto provide crude product (12 g), which
  6. temperatureto cool slightly
  7. temperaturethis mixture was heated for 1 hour at 50° C.
  8. filtrationfiltered through Celite
  9. waitthe solution was left
  10. customto crystallize for 18 hours

출처 및 근거

ORD 기록
ord-b4baa53a406c452ba4b1cf1b988fcdc1
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09200000B2

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