Toluene → HCID 25121517, compound

HRID 2400572Notes

Reaction equation

HRID 2400572 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)[N:14]=3)[O:10][N:9]=2)=[CH:4][CH:3]=1.[CH2:27]([NH:29][CH2:30][CH3:31])[CH3:28].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[CH2:27]([N:29]([CH2:30][CH3:31])[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)[N:14]=3)[O:10][N:9]=2)=[CH:4][CH:3]=1)[CH3:28]

Participants

8

Reactant 4

HCID 1140TolueneHCID 8021DiethylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 25118340HCID 25118340, compound

Product 1

HCID 25121517HCID 25121517, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(4-iodophenyl)-5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazole (Example 13, 250 mg, 0.55 mmol), diethylamine (113 μl, 1.1 mmol), sodium tert-butylat (74 mg, 0.77 mmol), palladium(II) acetate (25 mg, 0.11 mmol), 2-(dicyclohexylphosphino)-1,1′-biphenyl (19 mg, 0.06 mmol) and toluene (3 ml) was stirred at 80° C. for 15 h. The reaction mixture was cooled and water (100 mL) and ethyl acetate (100 mL) was added. The layers were separated and the organic layer was washed with water and brine and then dried with magnesium sulfate. The solvent was evaporated and the residue was purified, first using preparative HPLC, then via flash chromatography (silica, cyclohexane/ethyl acetate, 10:1→1:1) to afford the title compound as a white solid (42 mg, 19%): 1H NMR (400 MHz, CDCl3) 8.03 (d, 2H), 7.12 (d, 2H), 7.07 (d, 2H), 6.78 (s, 1H), 6.71 (d, 2H), 5.40 (s, 2H), 3.41 (quart, 4H), 2.32 (s, 3H), 2.25 (s, 3H), 1.20 (t, 6H); ES-MS m/z 402 (MH)+, HPLC RT (Method E) 2.68 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe layers were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was purified

Sources & evidence

ORD record
ord-926ee9c7c5c3494388db31f0f1657134
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

Loading…