Diisopropylethylamine → 4-Methoxy-1H-indole-2-carboxylic acid [1-(2-azepan-1-yl-ethyl)piperidin-4-yl]-amide

HRID 1929023Notes

Reaction equation

HRID 1929023 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:12]([OH:14])=O)[NH:7]2.Cl.Cl.Cl.[N:18]1([CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[N:18]1([CH2:25][CH2:26][N:27]2[CH2:28][CH2:29][CH:30]([NH:33][C:12]([C:6]3[NH:7][C:8]4[C:4]([CH:5]=3)=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][CH:9]=4)=[O:14])[CH2:31][CH2:32]2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9072484-Methoxy-1H-indole-2-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 668413931-(2-(Azepan-1-yl)ethyl)piperidin-4-amine trihydrochloride

Product 1

HCID 111769984-Methoxy-1H-indole-2-carboxylic acid [1-(2-azepan-1-yl-ethyl)piperidin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-Methoxy-1H-indole-2-carboxylic acid (930 mg, 4.86 mmol), amine 5 (1.63 g, 4.86 mmol) and DIEA (2.5 ml, 14.58 mmol) in 20 ml of DMF is treated with solid TBTU (1.56 g, 4.86 mmol). The mixture is stirred over night and then evaporated. The crude residue is dissolved in EtOAc and washed twice with sodium bicarbonate (10%). The aqueous layers are re-extracted with DCM, the combined organic layers are washed with brine and dried over sodium sulfate. The crude product is then purified by chromatography on silicagel using DCM (saturated with ammonia) and MeOH (from 0% to 2%).

Workup

  1. customevaporated
  2. dissolutionThe crude residue is dissolved in EtOAc
  3. washwashed twice with sodium bicarbonate (10%)
  4. extractionThe aqueous layers are re-extracted with DCM
  5. washthe combined organic layers are washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude product is then purified by chromatography on silicagel

Sources & evidence

ORD record
ord-652cea4be0634f3e812a4794cf27375d
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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