Hydrochloric Acid → Asp-9521

HRID 1894947Notes

Reaction equation

HRID 1894947 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([OH:14])=O)=[CH:6]2.[CH3:15][C:16]([OH:25])([CH3:24])[CH2:17][CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([N:21]1[CH2:22][CH2:23][CH:18]([CH2:17][C:16]([CH3:24])([OH:25])[CH3:15])[CH2:19][CH2:20]1)=[O:14])=[CH:6]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 204015-Methoxyindole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 184234282-Methyl-1-(piperidin-4-yl)propan-2-ol

Product 1

HCID 25210792Asp-9521Yield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 478 mg of 5-methoxyindole-2-carboxylic acid and 432 mg of 2-methyl-1-(piperidin-4-yl)-2-propanol in 8 mL of DMF were added 575 mg of 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride and 169 mg of 1-hydroxybenzotriazole, followed by stirring at room temperature for 1 day. 0.2M aqueous hydrochloric acid was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with 0.2M aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography [chloroform:methanol=1:0-24:1], and then crystallized from a mixture of ethyl acetate/diisopropyl ether to obtain 683 mg of 1-{1-[(5-methoxy-1H-indol-2-yl)carbonyl]piperidin-4-yl}-2-methylpropan-2-ol as a white crystal.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with 0.2M aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography [chloroform:methanol=1:0-24:1]
  6. customcrystallized from a mixture of ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-e1384e6c2519432a86f90b80e9d21c45
Source dataset
uspto-grants-2013_08
Patent number
US08513422B2

Reaction notes

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