4-(Trifluoromethoxy)benzoic acid → HCID 86711920, compound

HRID 1475226Notes

Reaction equation

HRID 1475226 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.O[NH:28][C:29]([C:31]1[N:35]=[C:34]([CH3:36])[N:33]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[CH:39]=2)[N:32]=1)=[NH:30]>C(Cl)Cl>[CH3:36][C:34]1[N:33]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[CH:39]=2)[N:32]=[C:31]([C:29]2[N:30]=[C:8]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:14])[F:13])=[CH:12][CH:11]=3)[O:10][N:28]=2)[N:35]=1

Participants

5

Reactant 3

HCID 676134-(Trifluoromethoxy)benzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 178432966HCID 178432966, compound

Product 1

HCID 86711920HCID 86711920, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
45 °C

Procedure

A solution of 4-(trifluoromethoxy)benzoic acid (85 mg, 0.41 mmol) and CDI (66 mg, 0.41 mmol) in DCM (2 mL) was stirred at RT for 4 h before being added to a solution of N-hydroxy-5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazole-3-carboximidamide (66 mg, 0.2 mmol) in DCM (1 mL). The reaction was then stirred at 45° C. for 6 h. The solvent was removed under reduced pressure, DMF (2 mL) was added and the reaction was stirred at 135° C. for 2 h. The reaction was then diluted with H2O (10 mL), extracted with 4:1 CHCl3:iPrOH (3×10 mL), dried with MgSO4 and concentrated under reduced pressure. The crude product was purified by pre-HPLC (Mobile phase: A=0.1% CF3CO2H/H2O, B=MeCN; Gradient: B=10%-40% in 30 min; Column: Waters C18) to afford 3-(5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-5-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (18 mg, 18%) as a yellow oil. MS (ES+) C24H24F3N7O2 requires: 499. found: 500 [M+H]+; 1H-NMR (600 MHz, CDCl3) δ ppm 8.34 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 7.23 (t, J=7.6 Hz, 1H), 6.86 (d, J=8.1 Hz, 1H), 6.77 (s, 1H), 6.67 (d, J=7.5 Hz, 1H), 5.40 (s, 2H), 3.18 (m, 4H), 2.54 (m, 4H), 2.49 (s, 3H), 2.33 (s, 3H).

Workup

  1. customThe solvent was removed under reduced pressure, DMF (2 mL)
  2. additionwas added
  3. stirringthe reaction was stirred at 135° C. for 2 h
  4. additionThe reaction was then diluted with H2O (10 mL)
  5. extractionextracted with 4:1 CHCl3
  6. dry with materialiPrOH (3×10 mL), dried with MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by pre-HPLC (Mobile phase
  9. waitGradient: B=10%-40% in 30 min

Sources & evidence

ORD record
ord-f6e7957f83ab4b748f5bd4f3d1fb1c35
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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