Hydrochloric Acid → 2-Methyl-1-(1-((5-methyl-1H-indol-2-yl)carbonyl)piperidin-4-yl)propan-2-ol

HRID 1894946Notes

Reaction equation

HRID 1894946 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.[CH3:14][C:15]([OH:24])([CH3:23])[CH2:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl>CN(C=O)C>[CH3:23][C:15]([OH:24])([CH3:14])[CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=3)=[O:13])[CH2:21][CH2:22]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 2591885-methyl-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 184234282-Methyl-1-(piperidin-4-yl)propan-2-ol

Product 1

HCID 252107562-Methyl-1-(1-((5-methyl-1H-indol-2-yl)carbonyl)piperidin-4-yl)propan-2-olYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1800 mg of 5-methylindole-2-carboxylic acid and 1500 mg of 2-methyl-1-(piperidin-4-yl)-2-propanol in 25 mL of DMF were added 2100 mg of 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride and 1500 mg of 1-hydroxybenzotriazole, followed by stirring at room temperature for 1 day. 0.5M aqueous hydrochloric acid was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with 0.5M 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=1:0-10:1], and then crystallized from a mixture of ethyl acetate/diisopropyl ether to obtain 2140 mg of 2-methyl-1-{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4-yl}propan-2-ol as a white crystal.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with 0.5M 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=1:0-10:1]
  6. customcrystallized from a mixture of ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-95f32f7b738142c5ae22c64ee2242768
Source dataset
uspto-grants-2013_08
Patent number
US08513422B2

Reaction notes

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