1,2-Dichloroethane → (E)-3-(6-aminopyridin-3-yl)-2-methyl-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide

HRID 1710584Notes

Reaction equation

HRID 1710584 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][C:6](/[CH:9]=[C:10](\[CH3:14])/[C:11]([OH:13])=O)=[CH:5][CH:4]=1.[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]1[CH2:25][NH:26][CH3:27].C1C=CC2N(O)N=NC=2C=1.O.CCN(CC)CC.C(Cl)CCl>CN(C=O)C.C(Cl)Cl>[NH2:2][C:3]1[N:8]=[CH:7][C:6](/[CH:9]=[C:10](\[CH3:14])/[C:11]([N:26]([CH3:27])[CH2:25][C:17]2[N:16]([CH3:15])[C:24]3[C:19]([CH:18]=2)=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:13])=[CH:5][CH:4]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 67343937(E)-3-(6-aminopyridin-3-yl)2-methylacrylic acid HCl salt

Product 1

HCID 57440853(E)-3-(6-aminopyridin-3-yl)-2-methyl-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamideYield 75%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (E)-3-(6-aminopyridin-3-yl)-2-methylacrylic acid HCl salt (0.5 g, 2.3 mmole) in dry 1:1 DMF/CH2Cl2 (30 mL) at RT was added 1-methyl-2-(methylaminomethyl)indole (0.42 g, 2.4 mmole), HOBt.H2O (0.32 g, 2.4 mmole), Et3N (0.66 mL, 4.7 mmole), and EDC (0.46 g, 2.4 mmole). After stirring for 24 hr the reaction was concentrated to dryness. The residue was taken up in ethyl acetate and the solution was washed with H2O, dried (Na2SO4), and concentrated under vacuum. Flash chromatography on silica gel (4% methanol/CHCl3) followed by trituration with ethyl acetate/hexane gave the title compound (0.55 g, 75%) as an off-white solid: LCMS (ES) m/e 335.2 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 7.96 (s, 1H), 732 (d, J=7.8 Hz, 1H), 7.48 (dd, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.14 (t, 1H), 7.03 (t, 1H), 6.46 (d, J=8.7 Hz, 1H), 6.43 (s, 1H), 6.40 (s, 1H), 6.17 (br s, 2H).

Workup

  1. concentrationwas concentrated to dryness
  2. washthe solution was washed with H2O
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ff57798287e54eedb5c0df57b28b8630
Source dataset
uspto-grants-2010_09
Patent number
US07790716B2

Reaction notes

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