1-Hydroxybenzotriazole → N-(1-benzylpiperidin-4-yl)-5-hydroxy-1H-indole-2-carboxamide

HRID 1091900Notes

Reaction equation

HRID 1091900 reaction equation
[OH: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.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:36]([N:43]1[CH2:48][CH2:47][CH:46]([NH2:49])[CH2:45][CH2:44]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C)C=O.C(N(CC)CC)C>[CH2:36]([N:43]1[CH2:48][CH2:47][CH:46]([NH:49][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([OH:1])=[CH:10][CH:9]=3)=[O:13])[CH2:45][CH2:44]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 889585-Hydroxyindole-2-carboxylic acidHCID 4158521-Benzyl-4-piperidylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 66589583N-(1-benzylpiperidin-4-yl)-5-hydroxy-1H-indole-2-carboxamideYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred mixture of 5-hydroxy-1H-indole-2-carboxylic acid (1.85 g, 10.43 mmol) in anhydrous dimethylformamide (15 mL) was added triethylamine (1.73 mL), 1-hydroxybenzotriazole (1.64 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.39 g) and 1-benzylpiperidin-4-ylamine (2.39 g, 12.54 mmol). The reaction mixture was stirred at room temperature over-night and then solvents were removed under reduced pressure, poured into water, filter the solid and washed with water. The solid was purified by silica gel column chromatography, eluted with CH2Cl2:MeOH (93:7) to afford 0.87 g (24%) of N-(1-benzylpiperidin-4-yl)-5-hydroxy-1H-indole-2-carboxamide as a white solid. 1H NMR (DMSO-d6, 300 MHz): δ 11.17(s, 1H), 8.72 (s, 1H), 8.07 (d, J=7.8 Hz, 1H), 7.7.29 (m, 6H), 6.91 (s, 1H), 6.82 (s, 1H), 6.68 (m, 1H), 3.75 (br s, 1H), 3.46 (s, 2H), 2.81 (d, J=11.4 Hz, 2H), 2.02 (t, J=10.8 Hz, 2H), 1.77 (m, 2H), 1.56 (m, 2H); LCMS (m/z): 350 (MH+).

Workup

  1. customsolvents were removed under reduced pressure
  2. additionpoured into water
  3. filtrationfilter the solid
  4. washwashed with water
  5. customThe solid was purified by silica gel column chromatography
  6. washeluted with CH2Cl2:MeOH (93:7)

Sources & evidence

ORD record
ord-5e90fdfc61114154a4719c9dc2a46fdf
Source dataset
uspto-grants-2012_03
Patent number
US08129390B2

Reaction notes

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