Dabco → 3-(7-{5-[3,4-bis(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acid

HRID 1512903Notes

Reaction equation

HRID 1512903 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[C:20]4[C:24]=3[NH:23][CH:22]=[C:21]4[CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH2:32]1N2CCN(CC2)C1.C(=O)(OC)OC>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[C:20]4[C:24]=3[N:23]([CH3:32])[CH:22]=[C:21]4[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 9237DabcoHCID 12021Dimethyl CarbonateHCID 59146185ethyl 3-(7-{5-[3,4-bis(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

Product 1

HCID 445484063-(7-{5-[3,4-bis(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acidYield 57.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 3-(7-{5-[3,4-bis(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (100 mg) (D67), DABCO (27 mg) and N,N-dimethylformamide (3 mL) was added to dimethyl carbonate (10 mL) successively. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 150° C. for 2 h. After cooling the reaction, the solvent was removed in vacuo. The residue was dissolved in tetrahydrofuran (5 mL) and methanol (5 mL), and then NaOH (48 mg) in water (5 mL) was added. The mixture was stir at 50° C. for 8 h. The organic solvent was removed and the mixture was acidified with HCl (1 M) solution to pH around 1. Extracted with EtOAc (60 mL), the organic layer was separated and the organic solvent was evaporated off. The residue was purified by Mass Directed Auto Prep to afford 3-(7-{5-[3,4-bis(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acid (E44) (56 mg). δH (DMSO-d6, 400 MHz): 2.60 (2H, t), 2.96 (2H, t), 3.62 (3H, s), 3.88 (6H, s), 7.17 (1H, t), 7.19 (1H, s), 7.22 (1H, d), 7.43 (1H, dd), 7.66 (1H, d), 7.79 (1H, dd), 7.82 (1H, dd), 12.12 (1H, s). MS (ES): C22H21N3O5 requires 407; found 408.2 (M+H+).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureheated in Biotage Initiator
  3. customnormal to 150° C.
  4. customfor 2 h
  5. temperatureAfter cooling
  6. customthe reaction
  7. customthe solvent was removed in vacuo
  8. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  9. additionmethanol (5 mL), and then NaOH (48 mg) in water (5 mL) was added
  10. customThe organic solvent was removed
  11. extractionExtracted with EtOAc (60 mL)
  12. customthe organic layer was separated
  13. customthe organic solvent was evaporated off
  14. customThe residue was purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-77a3e25194684e20bc8bc5c1f98fc057
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

Loading…