Triethylamine → 4-{5-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}pyridine

HRID 2400568Notes

Reaction equation

HRID 2400568 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15](Cl)=[O:16])[CH:3]=1.O[N:19]=[C:20]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[NH2:21].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl>ClCCl.C(OCC)(=O)C.O>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]2[O:16][N:21]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[N:19]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15326N'-Hydroxypyridine-4-carboximidamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 595047005-Methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbonyl chloride

Product 1

HCID 251179874-{5-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}pyridineYield 75.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbonyl chloride (Step 1, 65 mg, 0.26 mmol) in dichloromethane (4 mL) at 0° C. was added N′-hydroxypyridine-4-amidine (43 mg, 0.31 mmol) along with triethyl amine (0.073 mL). The mixture was stirred for 16 h at rt. The mixture was evaporated to dryness and DMF (3 mL) was added along with EDCl (75 mg, 0.392 mmol) and the mixture was stirred at 140° C. for 2 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 (2×200 mL) and then dried with magnesium sulfate. The solvent was evaporated and the residue was purified with an ISCO CombiFlash Companion using gradient elution from 100% hexane to 40% ethyl acetate in hexane to afford the title compound as a white solid (65 mg, 75%): 1H NMR (300 MHz, CD2Cl2) 8.80 (d, 2H), 8.20 (d, 2H), 7.20 (d, 2H), 7.10 (d, 2H), 6.82 (s, 1H), 5.40 (s, 2H), 2.35 (m, 6H); ES-MS m/z 332.25 (MH)+, HPLC RT (Method B) 3.34 min.

Workup

  1. customThe mixture was evaporated to dryness and DMF (3 mL)
  2. stirringthe mixture was stirred at 140° C. for 2 h
  3. temperatureThe reaction mixture was cooled
  4. customThe layers were separated
  5. washthe organic layer was washed with water (2×200 mL)
  6. dry with materialdried with magnesium sulfate
  7. customThe solvent was evaporated
  8. customthe residue was purified with an ISCO CombiFlash Companion
  9. washelution from 100% hexane to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-28b8dc49cbd7450dadc1e90fdada7fa8
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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