Dabco → HCID 44547607, compound

HRID 1512876Notes

Reaction equation

HRID 1512876 reaction equation
[CH2:1]1N2CCN(CC2)C1.[CH3:9][C:10]1[CH:11]=[C:12]([C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:33]=3[NH:32][CH:31]=[C:30]4[CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])[N:21]=2)[CH:13]=[N:14][C:15]=1[O:16][CH:17]([CH3:19])[CH3:18]>C(=O)(OC)OC.CN(C=O)C>[CH3:1][N:32]1[C:33]2[C:29](=[CH:28][CH:27]=[CH:26][C:25]=2[C:22]2[N:21]=[C:20]([C:12]3[CH:13]=[N:14][C:15]([O:16][CH:17]([CH3:19])[CH3:18])=[C:10]([CH3:9])[CH:11]=3)[O:24][N:23]=2)[C:30]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[CH:31]1

Participants

5

Reactant 2

HCID 9237DabcoHCID 59146130HCID 59146130, compound

Product 1

HCID 44547607HCID 44547607, compoundYield 25.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 12021Dimethyl CarbonateSolvent

Conditions

Temperature
70 °C

Procedure

DABCO (20 mg) was added to a solution of ethyl 3-[7-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate (D119) (188 mg) in dimethyl carbonate (2 mL) and DMF (0.2 mL). The resulting mixture was stirred at reflux for 1 day. 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 dissolved in iPrOH (8 mL) and water (8 mL). Sodium hydroxide (40 mg) was added to the mixture. The resulting mixture was heated at 70° C. for 30 mins. Then 0.5 M HCl solution was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by Mass Directed Auto Prep to afford 3-[1-methyl-7-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid (E17) (19 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 2.23 (3H, s), 2.60 (2H, t), 2.96 (2H, t), 3.62 (3H, s), 5.40 (1H, m), 7.16 (1H, d), 7.19 (1H, s), 7.43 (1H, d), 7.79 (1H, d), 8.29 (1H, s), 8.84 (1H, d), 12.12 (1H, br s). MS (ES): C23H24N4O4 requires 420; found 421.2 (M+H+).

Workup

  1. temperatureat reflux for 1 day
  2. temperatureAfter cooling
  3. customthe reaction was quenched with water
  4. extractionextracted with EtOAc for 3 times
  5. washThe combined organic solution was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe dried solution was concentrated
  8. dissolutionThe residue was dissolved in iPrOH (8 mL)
  9. additionSodium hydroxide (40 mg) was added to the mixture
  10. additionThen 0.5 M HCl solution was added until pH was about 6
  11. concentrationThe solvent was concentrated
  12. dissolutionthe residue was dissolved in water
  13. customThe precipitated solid was purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-8c1b7be20aca40788b6f99ffe1c73df6
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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