Pyridine → 2-Isobutyl-4-[2-(2-isobutyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridine

HRID 1908856Notes

Reaction equation

HRID 1908856 reaction equation
Cl.[CH2:2]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([CH3:15])[N:14]=1)[C:9](O)=[O:10])[CH:3]([CH3:5])[CH3:4].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:47]([C:51]1[CH:52]=[C:53]([CH:58]=[C:59]([CH3:61])[N:60]=1)[C:54]([NH:56][NH2:57])=O)[CH:48]([CH3:50])[CH3:49].N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>CN(C=O)C.CCOCC.C(Cl)Cl>[CH2:47]([C:51]1[CH:52]=[C:53]([C:54]2[O:10][C:9]([C:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:6]([CH2:2][CH:3]([CH3:5])[CH3:4])[CH:7]=3)=[N:57][N:56]=2)[CH:58]=[C:59]([CH3:61])[N:60]=1)[CH:48]([CH3:50])[CH3:49]

Participants

10

Reactant 6

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67026961HCID 67026961, compoundHCID 67027148HCID 67027148, compound

Product 1

HCID 584180192-Isobutyl-4-[2-(2-isobutyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridineYield 41.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-isobutyl-6-methyl-isonicotinic acid hydrochloride (41 mg, 0.178 mmol) and DIPEA (69 mg, 0.535 mmol) in DMF (2 mL) is added TBTU (57 mg, 0.178 mmol) at 0° C. The mixture is stirred for 30 min at 0° C. before 2-isobutyl-6-methyl-isonicotinic hydrazide (37 mg, 0.179 mmol) is added. Stirring is continued for 2 h. The mixture is diluted with ether (200 mL) and washed with 10% aq. citric acid solution (3×10 mL), sat. aq. NaHCO3-solution (3×10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated to give crude 2-isobutyl-6-methyl-isonicotinic acid N′-(2-isobutyl-6-methyl-pyridine-4-carbonyl)-hydrazide (70 mg) as a yellow oil; LC-MS: tR=0.60 min, [M+1]+=383.25. A part of this material (45 mg, 0.119 mmol) is dissolved in DCM (7 mL) and pyridine (47 mg, 0.595 mmol) followed by trifluoromethanesulfonic anhydride (37 mg, 0.131 mmol) is added at 0° C. The mixture is stirred for 2 h at 0° C. and 15 h at rt before it is diluted with DCM, washed with water, dried over MgSO4, filtered and the solvent of the filtrate is evaporated. The crude product is purified by prep. TLC with heptane:EA 2:3 to give 2-isobutyl-4-[2-(2-isobutyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridine (27 mg) as a colourless oil; LC-MS: tR=0.72 min, [M+1]+=365.54; 1H NMR (CDCl3): δ 0.99 (d, J=6.5 Hz, 12H), 2.19 (hept, J=7.0 Hz, 2H), 2.68 (s, 6H), 2.77 (d, J=7.3 Hz, 4H), 7.64 (s, 2H), 7.69 (s, 2H).

Workup

  1. additionis added
  2. washwashed with 10% aq. citric acid solution (3×10 mL), sat. aq. NaHCO3-solution (3×10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude 2-isobutyl-6-methyl-isonicotinic acid N′-(2-isobutyl-6-methyl-pyridine-4-carbonyl)-hydrazide (70 mg) as a yellow oil
  7. additionis added at 0° C
  8. stirringThe mixture is stirred for 2 h at 0° C. and 15 h at rt before it
  9. washwashed with water
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe solvent of the filtrate is evaporated
  13. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-fbf5a44a53b04a7fba2578f824afc5f3
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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