5-methyl-1H-pyrazole-3-carboxylic acid → 3-[4-(2-fluoropropan-2-yl)phenyl]-5-(5-methyl-1H-pyrazol-3-yl)-1,2,4-oxadiazole

HRID 2400563Notes

Reaction equation

HRID 2400563 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[C:4]([C:7]([OH:9])=O)[CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[F:32][C:33]([C:36]1[CH:41]=[CH:40][C:39]([C:42](=[N:44]O)[NH2:43])=[CH:38][CH:37]=1)([CH3:35])[CH3:34]>CN(C=O)C>[F:32][C:33]([C:36]1[CH:41]=[CH:40][C:39]([C:42]2[N:43]=[C:7]([C:4]3[CH:3]=[C:2]([CH3:1])[NH:6][N:5]=3)[O:9][N:44]=2)=[CH:38][CH:37]=1)([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 98225-methyl-1H-pyrazole-3-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 723094744-(2-fluoropropan-2-yl)-N'-hydroxybenzenecarboximidamide2×

Product 1

HCID 595047423-[4-(2-fluoropropan-2-yl)phenyl]-5-(5-methyl-1H-pyrazol-3-yl)-1,2,4-oxadiazoleYield 68.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mechanically stirred solution of 5-methyl-1H-pyrazole-3-carboxylic acid (1.59 g, 12.64 mmol) in dry DMF (64 mL) was added EDCl (2.42 g, 12.64 mmol), HOBT (1.71 g, 12.64 mmol) and 4-(2-fluoropropan-2-yl)-N′-hydroxybenzenecarboximidamide (Intermediate Q, 2.48 g, 12.64 mmol). The mixture was stirred at rt for 2 h, and then heated to 140° C. and stirred for additional 1 h. After being cooled to it, the solvent was removed under reduced pressure. Ethyl acetate (150 mL) and 2% aqueous citric acid solution (150 mL) were added, and the organic phase was separated and washed with saturated aqueous sodium bicarbonate solution (150 mL) and saturated aqueous sodium chloride solution. After drying over anhydrous magnesium sulfate and filtration, the solvent was removed in vacuo and the residue was purified by MPLC (silica, cyclohexane/ethyl acetate 3:1) to afford the title compound (2.48 g, 64%): 1H NMR (400 MHz, DMSO-d6) δ 13.54 (broad s, 1H), 8.08 (d, 2H), 7.62 (d, 2H), 6.81 (s, 1H), 2.33 (s, 3H), 1.72 (s, 3H), 1.68 (s, 3H); ES-MS m/z 287 (MH)+; HPLC RT (Method F) 2.19 min.

Workup

  1. temperatureheated to 140° C.
  2. stirringstirred for additional 1 h
  3. temperatureAfter being cooled to it
  4. customthe solvent was removed under reduced pressure
  5. additionEthyl acetate (150 mL) and 2% aqueous citric acid solution (150 mL) were added
  6. customthe organic phase was separated
  7. washwashed with saturated aqueous sodium bicarbonate solution (150 mL) and saturated aqueous sodium chloride solution
  8. dry with materialAfter drying over anhydrous magnesium sulfate and filtration
  9. customthe solvent was removed in vacuo
  10. customthe residue was purified by MPLC (silica, cyclohexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-18ca1218d2a74f6ca7a2accfde032a34
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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