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

反応式

HRID 1498036 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
40 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b4baa53a406c452ba4b1cf1b988fcdc1
出典データセット
uspto-grants-2015_12
特許番号
US09200000B2

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