Thionyl Chloride → 2-(4-{4-Methyl-5-[2-(trifluoromethyl)phenyl]-4h-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-5-(3,3,3-trifluoro-1-methylpropyl)-1,3,4-oxadiazole

HRID 2079837Notes

Reaction equation

HRID 2079837 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]([NH:27][NH:28][C:29](=[O:37])[CH:30]([CH3:36])[CH2:31][C:32]([F:35])([F:34])[F:33])=O)([CH2:21][CH2:22]1)[CH2:19][CH2:18]2.S(Cl)(Cl)=O>C1(C)C=CC=CC=1.CC#N>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:14])([F:16])[F:15])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]3[O:37][C:29]([CH:30]([CH3:36])[CH2:31][C:32]([F:34])([F:35])[F:33])=[N:28][N:27]=3)([CH2:21][CH2:22]1)[CH2:19][CH2:18]2

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 575723784-{-4-Methyl-5-[2-(trifluoromethyl)phenyl]-4h-1,2,4-triazol-3-yl}-n'-(4,4,4-trifluoro-2-methylbutanoyl)bicyclo[2.2.2]octane-1-carbohydrazide

Product 1

HCID 575723742-(4-{4-Methyl-5-[2-(trifluoromethyl)phenyl]-4h-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-5-(3,3,3-trifluoro-1-methylpropyl)-1,3,4-oxadiazole

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

To 13-B in toluene (3 mL) was added thionyl chloride (2 mL) and, fitted with a reflux condenser, the solution was heated to 85° C. under a nitrogen atmosphere. After 1 hour the solvent was stripped off in vacuo. The residue was dissolved in CH3CN (4 ml) and product was purified by Masslynx reverse phase chromatography eluting with a 10-90% CH3CN (0.1% TFA)/water (0.1% TFA) gradient. Solvent was removed in vacuo and the product free based from methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was washed with brine and dried over MgSO4. The solvent was removed and the product lyopholyzed from CH3CN and water to afford 13-C as a white solid. MS (ESI+)=514.22 (M+1); 1H NMR (500 MHz, CDCl3): δ 7.85-7.83 (m, 1 H), 7.72-7.68 (m, 2 H), 7.52 (t, 1 H), 3.48 (s, 3 H), 3.46 (m, 1 H), 2.86-2.74 (m, 1 H), 2.51-2.39 (m, 1 H), 2.28 (m, 6 H), 2.14 (m, 6 H), 1.50 (d, 3 H) ppm.

Workup

  1. customfitted with a reflux condenser
  2. customproduct was purified by Masslynx reverse phase chromatography
  3. washeluting with a 10-90% CH3CN (0.1% TFA)/water (0.1% TFA) gradient
  4. customSolvent was removed in vacuo
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-c9fd1cbf89004fd79765ea7977e82f70
Source dataset
uspto-grants-2011_04
Patent number
US07932280B2

Reaction notes

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