Dabco → 3-[1-methyl-6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid

HRID 1512940노트

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HRID 1512940 반응식
[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:33]=[C:32]4[C:28]([C:29]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[CH:30][NH:31]4)=[CH:27][CH:26]=3)[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:31]1[C:32]2[C:28](=[CH:27][CH:26]=[C:25]([C:22]3[N:21]=[C:20]([C:12]4[CH:13]=[N:14][C:15]([O:16][CH:17]([CH3:19])[CH3:18])=[C:10]([CH3:9])[CH:11]=4)[O:24][N:23]=3)[CH:33]=2)[C:29]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[CH:30]1

참가 물질

5

반응물 2

HCID 9237DabcoHCID 445470203-[6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid

생성물 1

HCID 445470213-[1-methyl-6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid수율 53.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 12021Dimethyl Carbonate용매

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온도
90 °C

실험 절차

DABCO (110 mg) was added to a solution of 3-[6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid (E85) (100 mg) in dimethyl carbonate (3 mL) and DMF (2 mL). The resulting mixture was heated at reflux for 5 days. 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 dissolved in iPrOH (3 mL) and water (3 mL). Sodium hydroxide (30 mg) was added to the mixture. The resulting mixture was heated at 90° C. for 1 hour. 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-6-(5-{5-methyl-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoic acid (E86) (55 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 2.24 (3H, s), 2.60 (2H, t), 2.95 (2H, t), 3.83 (3H, s), 5.41 (1H, m), 7.31 (1H, s), 7.74 (2H, m), 8.10 (1H, s), 8.29 (1H, d), 8.82 (1H, d), 12.10 (1H, br s). MS (ES): C23H24N4O4 requires 420; found 421.2 (M+H+).

후처리

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 5 days
  3. temperatureAfter cooling
  4. customthe reaction was quenched with water
  5. extractionextracted with EtOAc for 3 times
  6. washThe combined organic solution was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationThe dried solution was concentrated
  9. dissolutionThe residue was dissolved in iPrOH (3 mL)
  10. additionSodium hydroxide (30 mg) was added to the mixture
  11. additionThen 0.5 M HCl solution was added until pH was about 6
  12. concentrationThe solvent was concentrated
  13. dissolutionthe residue was dissolved in water
  14. customThe precipitated solid was purified by Mass Directed Auto Prep

출처 및 근거

ORD 기록
ord-66f5efda60284b86a860a6efc2ed3495
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217028B2

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