3,4-Diethoxybenzoic acid → 5-(3,4-Diethoxyphenyl)-3-(1H-indol-5-yl)-1,2,4-oxadiazole

HRID 710389Notes

Reaction equation

HRID 710389 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[C:7]([OH:9])=O)[CH3:2].O[NH:17][C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][CH:24]=[CH:23]2)=[NH:19].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[O:9][N:19]=[C:18]([C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]=[CH:23]4)[N:17]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2]

Participants

9

Reactant 5

HCID 794173,4-Diethoxybenzoic acidHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 2733179PyBroPHCID 178513238HCID 178513238, compound

Product 1

HCID 251103335-(3,4-Diethoxyphenyl)-3-(1H-indol-5-yl)-1,2,4-oxadiazoleYield 53%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 3,4-diethoxybenzoic acid (0.11 g; 0.52 mmol), and the product of Example 7, Step C (0.09 g; 10.52 mmol) in anhydrous THF (2 ml), PyBroP (0.25 g; 0.53 mmol) was added, followed by DIPEA (0.21 ml; 1.2 mmol), with stirring, at room temperature under N2. After overnight stirring, the mixture was diluted to 15 ml with EtOAc, washed with saturated NH4Cl (3×5 ml), brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by FCC (SiO2, EtOAc) to give the coupling product. This was suspended in anhydrous toluene (3 ml) and 1M TBAF was added. The resulting mixture was refluxed for 1 h under N2, cooled to room temperature and diluted to 15 ml with EtOAc, washed with H2O, brine, dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness. The residue was purified by crystallization from MeOH, to give the title compound (0.096 g; 53%), as a colourless solid. 1H-NMR (CDCl3) 1.5 (m, 6H); 4.19 (m, 4H); 6.66 (s, 1H); 6.98 (d, 1H, J=8.4 Hz); 7.26 (m, 1H); 7.47 (d, 1H, J=8.5 Hz); 7.71 (d, 1H, J=1.8 Hz); 7.8 (dd, 1H, J=1.8, 8.5 Hz); 8.0 (dd, 1H, J=1.3, 8.5 Hz); 8.37 (broad s, 1H); 8.5 (s, 1H).

Workup

  1. stirringAfter overnight stirring
  2. washwashed with saturated NH4Cl (3×5 ml), brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness under reduced pressure
  6. customthe residue was purified by FCC (SiO2, EtOAc)
  7. customto give the coupling product
  8. temperatureThe resulting mixture was refluxed for 1 h under N2
  9. temperaturecooled to room temperature
  10. washwashed with H2O, brine
  11. dry with materialdried over anhydrous MgSO4
  12. filtrationfiltered
  13. customfiltrate evaporated to dryness
  14. customThe residue was purified by crystallization from MeOH

Sources & evidence

ORD record
ord-eedb0de32eae488aa8cf53faf1a061d2
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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