1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole

HRID 1512763Notes

Reaction equation

HRID 1512763 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O[NH:37][C:38]([C:40]1[CH:41]=[CH:42][CH:43]=[C:44]2[C:48]=1[NH:47][CH:46]=[CH:45]2)=[NH:39].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:39]=[C:38]([C:40]3[CH:41]=[CH:42][CH:43]=[C:44]4[C:48]=3[NH:47][CH:46]=[CH:45]4)[N:37]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178513271HCID 178513271, compound

Product 1

HCID 591461207-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indoleYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (5.2 g) in tetrahydrofuran (15 mL) stirred at room temp was added EDCI (5.8 g) and HOBT (4.6 g). The reaction mixture was stirred at room temperature for 2 h. Then N-hydroxy-1H-indole-7-carboximidamide (3.5 g) was added. The reaction mixture was stirred at 60° C. for 2 h, and then TBAF (15.7 g) 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, solvent was removed. Water (200 mL) and ethanol (50 mL) was added. The precipitate was collected, washed with acetonitrile and dried in vacuo to afford 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D51) (5.1 g) as a yellow solid. δH (CDCl3, 400 MHz): 1.47 (6H, d), 4.70-4.76 (1H, m), 6.68 (1H, dd), 7.08 (1H, d), 7.29 (1H, t), 7.40 (1H, t), 7.85 (1H, d), 8.11 (1H, dd), 8.13 (1H, dd), 8.30 (1H, d), 9.86 (1H, s). MS (ES): C19H16ClN3O2 requires 353; found 354.1 (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, solvent
  8. customwas removed
  9. additionWater (200 mL) and ethanol (50 mL) was added
  10. customThe precipitate was collected
  11. washwashed with acetonitrile
  12. customdried in vacuo

Sources & evidence

ORD record
ord-ac0b52027357426aae8873416f021fe0
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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