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

HRID 1921061
Notes
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Reaction equation

HRID 1921061 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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)acrylamide
Yield 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 (035 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-431411eba6304346a8c695373576960a
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08173646B2

Reaction notes

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