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

Reaktionsgleichung

Reaktionsgleichung von HRID 1498036
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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b4baa53a406c452ba4b1cf1b988fcdc1
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09200000B2

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