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

HRID 225944Notes

Reaction equation

HRID 225944 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5]C=CC=2)[CH:3]=[CH:2]1.[NH2:10][C:11]1[N:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19]([OH:21])=O)=[CH:13][CH:12]=1.[CH3:22]CN(CC)CC.[CH:29]1[CH:30]=[CH:31][C:32]2N(O)N=[N:35][C:33]=2[CH:34]=1.O.C(Cl)CCl>CN(C=O)C.C(Cl)Cl>[NH2:10][C:11]1[N:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19]([N:1]([CH2:2][C:3]2[C:32]3[C:33](=[CH:34][CH:29]=[CH:30][CH:31]=3)[N:35]([CH3:22])[C:4]=2[CH3:5])[CH3:9])=[O:21])=[CH:13][CH:12]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 798IndoleHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acid

Product 1

HCID 60208937(E)-3-(6-aminopyridin-3-yl)-N-(1,2-dimethyl-1H-indol-3-ylmethyl)-N-methylacrylamideYield 97%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of 1,2-methyl-3-methylaminomethyl)-1H-indole (0.8 g, 4.2 mmole) in 1:1 DMF/CH2Cl2 (30 mL) at RT was added (E)-3-(6-aminopyridin-3-yl)acrylic acid (0.7 g, 4.3 mmole), Et3N (0.61 mL, 4.3 mmole), HOBt.H2O (0.58 g, 4.3 mmole) and EDC (0.83 g, 4.3 mmole). After 16 h the reaction was concentrated under vacuum and the residue was taken up in EtOAc (100 mL). The solution was washed with 1.0 N Na2CO3 (100 mL) then with brine, dried (Na2SO4), and concentrated. Purification by flash chromatography on silica gel (4% MeOH/CHCl3) followed by trituration with 1:1 Et2O/petroleum ether and drying under vacuum gave the tide compound (1.36 g, 97%) as an off-white solid: MS (ES) m/e 335.2 (M+H)+.

Workup

  1. concentrationAfter 16 h the reaction was concentrated under vacuum
  2. washThe solution was washed with 1.0 N Na2CO3 (100 mL)
  3. dry with materialwith brine, dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (4% MeOH/CHCl3)
  6. customdrying under vacuum

Sources & evidence

ORD record
ord-2a74656c0a4a4ab88b23df9375073237
Source dataset
uspto-grants-2009_07
Patent number
US07557125B2

Reaction notes

Loading…