Water → (E)-3-(6-amino-4-methylpyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide

HRID 225934Notes

Reaction equation

HRID 225934 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)=[C:5]([CH3:14])[CH:4]=1.CCN(CC)CC.[CH3:22][N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]1[CH2:32][NH:33][CH3:34].C1C=CC2N(O)N=NC=2C=1.O.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(Cl)Cl>[NH2:2][C:3]1[N:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([N:33]([CH3:34])[CH2:32][C:24]2[N:23]([CH3:22])[C:31]3[C:26]([CH:25]=2)=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:13])=[C:5]([CH3:14])[CH:4]=1

Participants

8

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 67343018(E)-3-(6-Amino4-methylpyridin-3-yl)acrylic acid HCl salt

Product 1

HCID 9819064(E)-3-(6-amino-4-methylpyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (E)-3-(6amino-4-methylpyridin-3-yl)acrylic acid HCl salt (0.70 g, 3.3 mmole) in 1:1 DMF/CH2Cl2 (30 mL) was added Et3N (0.42 mL, 3 mmole), 1-methyl-2-(methylaminomethyl)indole (0.50 g, 2.9 mmole), HOBt.H2O (0.41 g, 3 mmole), and DCC (0.70 g, 3 mmole). After stirring at RT for 16 hr the reaction was concentrated under vacuum. The residue was taken up in ethyl acetate and filtered. The filtrate was washed with 1.0 N Na2CO3 then with brine, dried (Na2SO4), and concentrated under vacuum. Purification by flash chromatography on silica gel (4% methanol/CHCl3) gave the title compound (0.74 g, 74%) as a pale yellow solid: LCMS (ES) m/e 335.2 (M+H)+.

Workup

  1. concentrationwas concentrated under vacuum
  2. filtrationfiltered
  3. washThe filtrate was washed with 1.0 N Na2CO3
  4. dry with materialwith brine, dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customPurification by flash chromatography on silica gel (4% methanol/CHCl3)

Sources & evidence

ORD record
ord-8cb9fbf3296f40e589443e4366af89cf
Source dataset
uspto-grants-2009_07
Patent number
US07557125B2

Reaction notes

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