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 1907202

Reaction equation

HRID 1907202 reaction equation
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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4ff923a21019497eaffdd15378adc867
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Linked notes

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