1,2-Dichloroethane → 6-bromo-N-((6-(hydroxymethyl)-2-methoxy-4-methylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

HRID 873385Notes

Reaction equation

HRID 873385 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([CH3:13])=[CH:5][C:6]([CH2:11][OH:12])=[N:7][C:8]=1[O:9][CH3:10].[Br:14][C:15]1[CH:16]=[C:17]([C:28](O)=[O:29])[C:18]2[C:19]([CH3:27])=[CH:20][N:21]([CH:24]([CH3:26])[CH3:25])[C:22]=2[CH:23]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl.CN(C=O)C.CCOC(C)=O>[Br:14][C:15]1[CH:16]=[C:17]([C:28]([NH:1][CH2:2][C:3]2[C:8]([O:9][CH3:10])=[N:7][C:6]([CH2:11][OH:12])=[CH:5][C:4]=2[CH3:13])=[O:29])[C:18]2[C:19]([CH3:27])=[CH:20][N:21]([CH:24]([CH3:25])[CH3:26])[C:22]=2[CH:23]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 67468012(5-(Aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methanolHCID 674686786-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid

Product 1

HCID 674661066-bromo-N-((6-(hydroxymethyl)-2-methoxy-4-methylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamideYield 100%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methanol (0.29 g, 1.591 mmol), 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (0.48 g, 1.621 mmol), and HOAt (0.22 g, 1.616 mmol) in Dichloromethane (15 mL) and DMF (5 mL) was added EDC free base (0.30 g, 1.932 mmol). The reaction was stirred at RT for 3 h then evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 20% EtOAc in CH2Cl2) to give the product 6-bromo-N-((6-(hydroxymethyl)-2-methoxy-4-methylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (0.73 g, 1.586 mmol, 100% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.46 (t, J=4.9 Hz, 1 H), 7.77 (d, J=1.8 Hz, 1 H), 7.33 (d, J=1.0 Hz, 1 H), 6.99 (d, J=1.5 Hz, 1 H), 6.90 (s, 1 H), 5.31 (t, J=5.9 Hz, 1 H), 4.74 (quin, J=6.6 Hz, 1 H), 4.45 (d, J=5.1 Hz, 1 H), 4.43 (d, J=5.8 Hz, 2 H), 3.83 (s, 3 H), 2.40 (s, 3 H), 2.10 (s, 3 H), 1.38 (d, J=6.8 Hz, 6 H). MS(ES)+m/e 460.2 [M+H]+.

Workup

  1. customthen evaporated to dryness under vacuum
  2. customThe remaining was purified by silica gel chromatography (Analogix

Sources & evidence

ORD record
ord-6d1272ae59c448008c331d633f7bcce3
Source dataset
uspto-grants-2015_03
Patent number
US08975291B2

Reaction notes

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