1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole

HRID 1512804Notes

Reaction equation

HRID 1512804 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:22][C:23]1[CH:24]=[C:25]([C:33]([OH:35])=O)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:32])[CH3:31].O[NH:37][C:38]([C:40]1[CH:48]=[C:47]2[C:43]([CH:44]=[CH:45][NH:46]2)=[CH:42][CH:41]=1)=[NH:39].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]([C:33]2[O:35][N:39]=[C:38]([C:40]3[CH:48]=[C:47]4[C:43]([CH:44]=[CH:45][NH:46]4)=[CH:42][CH:41]=3)[N:37]=2)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:31])[CH3:32]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178513228HCID 178513228, compound

Product 1

HCID 591460766-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indoleYield 104.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

EDCI (1.17 g) and HOBT (1.01 g) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (657 mg) in THF (5 mL) at RT. The resulting solution was stirred for 30 min. N-hydroxy-1H-indole-6-carboximidamide (D100) (1.00 g) in THF (5 mL) was added and the reaction mixture was stirred at RT for 2 hours. TBAF (3.2 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 90 min. After cooling, the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford 6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D101) (1.13 g) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.47 (6H, d), 5.51 (1H, m), 6.65 (1H, s), 7.37 (1H, t), 7.76 (1H, d), 7.93 (1H, d), 8.26 (1H, s), 8.42 (2H, d), 8.90 (1H, d). MS (ES): C18H15ClN4O2 requires 354. found 355.1 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 2 hours
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 120° C.
  5. customfor 90 min
  6. temperatureAfter cooling
  7. customthe reaction was quenched with water
  8. extractionextracted with EtOAc for 3 times
  9. washThe combined organic solution was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationThe dried solution was concentrated
  12. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-65f208f1ab4d4b68a8dd0842ff3468b1
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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