1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-(7-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

HRID 1512751Notes

Reaction equation

HRID 1512751 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:22][CH:23]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([OH:34])=O)=[CH:28][C:27]=1[O:35][CH3:36])[CH3:24].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-]>C1COCC1>[CH3:24][CH:23]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[O:34][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:28][C:27]=1[O:35][CH3:36])[CH3:22]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 67025414HCID 67025414, compoundHCID 178506492HCID 178506492, compound

Product 1

HCID 59146142Ethyl 3-(7-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoateYield 88.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

EDCI (289 mg) and HOBT (220 mg) were added to a solution of 6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinecarboxylic acid (152 mg) in THF (3 mL) at RT. The resulting solution was stirred for 30 mins. Ethyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (250 mg) in THF (3 mL) was added and the reaction mixture was stirred at RT for 2 hours. TBAF (910 mg) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 90 mins. After cooling, the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography (20% EtOAc in hexane) to afford ethyl 3-(7-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D38) (286 mg) as a pale yellow solid. MS (ES): C24H26N4O5 requires 450; found 451.2 (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 mins
  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 (20% EtOAc in hexane)

Sources & evidence

ORD record
ord-c7cb0addf14e46d99db2a90b4a01e1c4
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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