1,2-Dichloroethane → 2-[2-(4-Methoxyphenyl)ethyl]-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]nicotinamide

HRID 1581684Notes

Reaction equation

HRID 1581684 reaction equation
C(Cl)CCl.[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]2[N:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([OH:19])=O)=[CH:9][CH:8]=1.[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[C:26]1[CH2:34][NH:35][CH3:36].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH3:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][C:15]2[N:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([N:35]([CH3:36])[CH2:34][C:26]2[N:25]([CH3:24])[C:33]3[C:28]([CH:27]=2)=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:19])=[CH:11][CH:12]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 121253972-[2-(4-Methoxyphenyl)ethyl]nicotinic acid

Product 1

HCID 99315542-[2-(4-Methoxyphenyl)ethyl]-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]nicotinamideYield 90.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

EDC (0.60 g, 3.16 mmole) was added to a solution of 2-[2-(4-methoxyphenyl)ethyl]nicotinic acid (0.81 g, 3.16 mmole), 1-methyl-2-(methylaminomethyl)indole (0.50 g, 2.87 mmole), HOBt.H2O (0.43 g, 3.16 mmole), and diisopropylethylamine (0.55 mL, 3.16 mmole) in DMF (15 mL) at RT. The reaction was stirred overnight, then was diluted with H2O and extracted with EtOAc. Drying (Na2SO4), concentration, and flash chromatography on silica gel (5% MeOH/CHCl3) gave the title compound (1.07 g, 90%) as a viscous yellow oil: 1H NMR (300 MHz, DMSO-d6) δ 8.63 (m, 1H), 7.22-7.61 (m, 8H), 6.97 (d, J=8.1 Hz, 1H), 6.63 (d, J=8.1 Hz, 1H), 6.52 (s, 1H), 3.80 (s, 3H), 3.78 (m, 2H), 3.72 (s, 2H), 3.16 (m, 2H), 3.03 (s, 3H), 2.57 (s, 3H), MS (ES) m/e 414 (M+H)+. Anal. Calcd for C26H27N3O2: C, 75.52; H, 6.58: N, 10.16. Found C, 75.84; H, 6.68; N, 9.76.

Workup

  1. customat RT
  2. extractionextracted with EtOAc
  3. customDrying
  4. concentration(Na2SO4), concentration, and flash chromatography on silica gel (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-fb9f71c9dafb43c99233e436fb20ca94
Source dataset
uspto-grants-2004_05
Patent number
US06730684B1

Reaction notes

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