Pyridine → HCID 86668345, compound

HRID 1189524Notes

Reaction equation

HRID 1189524 reaction equation
[CH3:1][C:2]([OH:6])([C:4]#[CH:5])[CH3:3].Cl[C:8](Cl)([O:10]C(=O)OC(Cl)(Cl)Cl)Cl.N1C=CC=CC=1.[F:25][C:26]([F:47])([F:46])[O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([NH2:45])=[CH:41][CH:40]=3)=[N:35]2)=[CH:30][CH:29]=1.NC1C=CC=CC=1>C(Cl)Cl>[CH3:1][C:2]([O:6][C:8](=[O:10])[NH:45][C:42]1[CH:43]=[CH:44][C:39]([C:36]2[N:37]=[CH:38][N:34]([C:31]3[CH:30]=[CH:29][C:28]([O:27][C:26]([F:25])([F:46])[F:47])=[CH:33][CH:32]=3)[N:35]=2)=[CH:40][CH:41]=1)([CH3:3])[C:4]#[CH:5]

Participants

7

Reactant 5

HCID 1049Pyridine2×HCID 6115AnilineHCID 82582-Methyl-3-butyn-2-olHCID 94429TriphosgeneHCID 578244904-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)aniline

Product 1

HCID 86668345HCID 86668345, compoundYield 91.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
23 °C

Procedure

2-Methyl-3-butyn-2-ol (48 μL, 0.44 mmol) was added to a solution of triphosgene (42 mg, 0.14 mmol) and pyridine (38 μL, 0.47 mmol) in CH2Cl2 (1.0 mL) at 23° C. Gas evolution was observed during addition of the alcohol, and a precipitate was observed to form. The resulting slurry was stirred at 23° C. for 1 h. Stirring was ceased, the solid was allowed to settle to the bottom of the flask, and the supernatant was added via cannula to a slurry of 4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenylamine (100 mg, 0.312 mmol) and pyridine (38 μL, 0.47 mmol) in CH2Cl2 (1.0 mL) at 23° C. A thick precipitate was observed to form. At this point, TLC analysis indicated some starting material remained, so an equivalent amount of triphosgene/pyridine/alcohol was combined as above, and the resulting supernatant was again added to the aniline mixture. After stirring for another 3 h at 23° C., the reaction mixture was diluted with 30% EtOAc/hexanes (10 mL), and a fine white precipitate was filtered on a coarse frit. The clear yellow filtrate was concentrated, and the resulting yellow oil was purified by silica gel chromatography (Biotage 10 g SNAP column, eluted with a 10% to 25% to 50% EtOAc/hexanes gradient) to provide the title compound (55 mg, 41%) as a white solid: mp 164-165° C.; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 8.13 (d, J=8.7 Hz, 2H), 7.79 (d, J=9.0 Hz, 2H), 7.53 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.8 Hz, 2H), 6.73 (s, 1H), 2.61 (s, 1H), 1.77 (s, 6H); ESIMS m/z 431 (M+H); HRMS-ESI (m/z): [M]+ calcd for C21H17F3N4O3, 430.125. found, 430.126.

Workup

  1. customto form
  2. stirringStirring
  3. customto form
  4. stirringAfter stirring for another 3 h at 23° C.
  5. filtrationa fine white precipitate was filtered on a coarse frit
  6. concentrationThe clear yellow filtrate was concentrated
  7. customthe resulting yellow oil was purified by silica gel chromatography (Biotage 10 g SNAP column
  8. washeluted with a 10% to 25% to 50% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-1b366153e4ca465e8fcdf6d6fc8c7879
Source dataset
uspto-grants-2014_03
Patent number
US08674109B2

Reaction notes

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