Ethyl 3-[{[4-({1-[5-(6-methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoate → 3-[{[4-({1-[5-(6-Methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid

HRID 1877303Notes

Reaction equation

HRID 1877303 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([CH3:14])=[C:11]([CH:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([N:29]([CH3:37])[CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[O:28])=[CH:23][CH:22]=3)[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:10]=2)=[CH:5][CH:4]=1>CC(O)C.CCCCCC>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([CH3:14])=[C:11]([CH:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]([N:29]([CH3:37])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:28])=[CH:25][CH:26]=3)[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:10]=2)=[CH:5][CH:4]=1

Participants

3

Reactant 1

HCID 68512510Ethyl 3-[{[4-({1-[5-(6-methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoate

Product 1

HCID 252567363-[{[4-({1-[5-(6-Methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acidYield 94%

Reagents, catalysts & solvents 1

HCID 21585144Isopropanol hexaneSolvent

Procedure

Ethyl 3-[{[4-({1-[5-(6-methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoate (12.0 g) which is a synthetic intermediate in Example 149 was dissolved in 2-propanol-hexane (8:2, volume ratio), and the solution was subjected to HPLC using CHIRALPAK AD (50 mmID×500 mmL, manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.) and eluted with 2-propanol-hexane (8:2, volume ratio) as mobile phase at 30° C., a flow rate 60 mL/min. The fractions showing a peak with retention time 44.7 min were collected, and concentrated. The obtained amorphous compound (5.58 g) was dissolved in ethanol (20 mL) and tetrahydrofuran (20 mL) and 1N lithium hydroxide (20 mL) was added, and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and water (30 mL) was added. The mixture was neutralized with 1N hydrochloric acid under ice-cooling, and stirred for 1 hr. The resulting precipitate was collected by filtration and dried to give the title compound (5.0 g, 94%).

Workup

  1. washeluted with 2-propanol-hexane (8:2, volume ratio) as mobile phase at 30° C.
  2. customwere collected
  3. concentrationconcentrated
  4. dissolutionThe obtained amorphous compound (5.58 g) was dissolved in ethanol (20 mL)
  5. additiontetrahydrofuran (20 mL) and 1N lithium hydroxide (20 mL) was added
  6. customThe solvent was evaporated under reduced pressure, and water (30 mL)
  7. additionwas added
  8. temperaturecooling
  9. stirringstirred for 1 hr
  10. filtrationThe resulting precipitate was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-a25fb8c71cb9487d8f74d078df21bd71
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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