1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

HRID 1512775Notes

Reaction equation

HRID 1512775 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].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O[NH:38]/[C:39](=[N:56]\[H])/[C:40]1[CH:41]=[CH:42][CH:43]=[C:44]2[C:48]=1[NH:47][CH:46]=[C:45]2[CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[O:9][N:56]=[C:39]([C:40]3[CH:41]=[CH:42][CH:43]=[C:44]4[C:48]=3[NH:47][CH:46]=[C:45]4[CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[N:38]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 794173,4-Diethoxybenzoic acidHCID 2724141Tetrabutylammonium FluorideHCID 178506492HCID 178506492, compound

Product 1

HCID 59146111Ethyl 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoateYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,4-bis(ethyloxy)benzoic acid (631 mg) in tetrahydrofuran (15 mL) stirred at room temperature was added EDCI (767 mg) and HOBT (613 mg). The reaction mixture was stirred for 2 h. Then ethyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (551 mg) was added. The reaction mixture was stirred at 60° C. for 2 h, and then TBAF (2092 mg) was added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 130° C. for 3 h. After cooling the reaction, the solvent was removed. Water (90 mL) and ethanol (30 mL) was added to the residue, a yellow solid was formed, filtered and dried in vacuo to afford the product ethyl 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D66) (706 mg). δH (CDCl3, 400 MHz): 1.26 (3H, t), 1.52-1.57 (6H, m), 2.76 (2H, t), 3.18 (2H, t), 4.16 (2H, q), 4.19-4.28 (4H, m), 7.02 (1H, d), 7.20 (1H, d), 7.28 (1H, t), 7.74 (1H, d), 7.81 (1H, d), 7.86 (1H, dd), 8.14 (1H, dd), 9.64 (1H, s). MS (ES): C25H27N3O5 requires 449. found 450.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 2 h
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 130° C.
  5. customfor 3 h
  6. temperatureAfter cooling
  7. customthe reaction
  8. customthe solvent was removed
  9. additionWater (90 mL) and ethanol (30 mL) was added to the residue
  10. customa yellow solid was formed
  11. filtrationfiltered
  12. customdried in vacuo

Sources & evidence

ORD record
ord-3cca199ce1c1417f9024360f51c67981
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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