1,2-Dichloroethane → (E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)acrylamide

HRID 18323Notes

Reaction equation

HRID 18323 reaction equation
Cl.[CH3:2][O:3][C:4]([CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]([OH:18])=O)=[CH:10][CH:9]=1)=[O:5].[CH3:19][C:20]1[NH:21][C:22]2[C:27]([C:28]=1[CH2:29][NH:30][CH3:31])=[CH:26][CH:25]=[CH:24][CH:23]=2.CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.O.C(Cl)CCl>CN(C=O)C.C(Cl)Cl>[CH3:2][O:3][C:4]([CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]([N:30]([CH3:31])[CH2:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][C:20]=2[CH3:19])=[O:18])=[CH:10][CH:9]=1)=[O:5]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 10954023N-Methyl-N-[(2-methyl-1H-indol-3-yl)methyl]amineHCID 66905135(e)-3-[6-[n-(Methoxycarbonylmethyl)amino]pyridin-3-yl]acrylic acid hydrochloride salt

Product 1

HCID 10363109(E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)acrylamideYield 73%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]acrylic acid hydrochloride salt (2.0 g, 7.3 mmole) in 1:1 DMF/CH2Cl2 (100 mL) was added 2-methyl-3-(methylaminomethyl)indole (1.3 g, 7.5 mmole), Et3N (2.1 mL, 15 mmole), and HOBt H2O (1.0 g, 7.4 mmole), followed by EDC (1.4 g, 7.3 mmole). After stirring at room temperature for 18 h the reaction was concentrated to dryness. The residue was taken up in EtOAc, and the solution was washed with H2O then brine, dried (Na2SO4), and concentrated under vacuum. The remaining residue was purified by flash chromatography on silica gel (4% MeOH/CHCl3) to give the title compound (2.08 g, 73%) as an off-white solid: MS (ES) m/e 393.2 (M+H)+.

Workup

  1. concentrationwas concentrated to dryness
  2. washthe solution was washed with H2O
  3. dry with materialbrine, dried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. customThe remaining residue was purified by flash chromatography on silica gel (4% MeOH/CHCl3)

Sources & evidence

ORD record
ord-1964a57e758b4e5b9bcced78f01098d3
Source dataset
uspto-grants-2010_06
Patent number
US07741339B2

Reaction notes

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