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

HRID 1512750Notes

Reaction equation

HRID 1512750 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[C:35]([F:38])([F:37])[F:36])[CH3:24].O[NH:40]/[C:41](=[N:58]\[H])/[C:42]1[CH:43]=[CH:44][CH:45]=[C:46]2[C:50]=1[NH:49][CH:48]=[C:47]2[CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54].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:58]=[C:41]([C:42]3[CH:43]=[CH:44][CH:45]=[C:46]4[C:50]=3[NH:49][CH:48]=[C:47]4[CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])[N:40]=2)=[CH:28][C:27]=1[C:35]([F:38])([F:37])[F:36])[CH3:22]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 670252766-[(1-Methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinecarboxylic acidHCID 178506492HCID 178506492, compound

Product 1

HCID 59146041ethyl 3-(7-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoateYield 42.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

EDCI (153 mg) and HOBT (132 mg) were added to a solution of 6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinecarboxylic acid (100 mg) in THF (2.5 mL). The mixture was stirred at room temperature for 0.5 hour, followed by addition of ethyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (165 mg) in THF (2.5 mL). The resulting mixture was stirred at room temperature for 1 hour, followed by addition of TBAF (418 mg). The reaction vessel was sealed and the reaction mixture was stirred at 120° C. in the microwave for 1.5 h. THF was removed. The residue was dissolved in EtOAc. The organic solution was washed with saturated aqueous sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford ethyl 3-(7-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D37) (83 mg) as a white solid. δH (CDCl3, 400 MHz): 1.24 (3H, t), 1.45 (6H, d), 2.74 (2H, t), 3.17 (2H, t), 4.15 (2H, q), 5.58 (1H, m), 7.19 (1H, d), 7.29 (1H, d), 7.82 (1H, d), 8.12 (1H, dd), 8.64 (1H, d), 9.17 (1H, d), 9.55 (1H, s); MS (ES): C24H23F3N4O4 requires 488; found 489.2 (M+H+).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1 hour
  2. customThe reaction vessel was sealed
  3. stirringthe reaction mixture was stirred at 120° C. in the microwave for 1.5 h
  4. customTHF was removed
  5. dissolutionThe residue was dissolved in EtOAc
  6. washThe organic solution was washed with saturated aqueous sodium bicarbonate solution
  7. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  8. concentrationThe dried solution was concentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e56b8e25a59340458f1d6d33bf07edf3
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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