1,2-Dichloroethane → (E)-N-[1-(2-hydroxyethyl)-1H-indol-3-ylmethyl]-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

HRID 1362144Notes

Reaction equation

HRID 1362144 reaction equation
C(Cl)CCl.Cl.[O:6]=[C:7]1[NH:16][C:15]2[N:14]=[CH:13][C:12](/[CH:17]=[CH:18]/[C:19]([OH:21])=O)=[CH:11][C:10]=2[CH2:9][CH2:8]1.[OH:22][CH2:23][CH2:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH2:34][NH:35][CH3:36])=[CH:26]1.C1C=CC2N(O)N=NC=2C=1.O.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:22][CH2:23][CH2:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH2:34][N:35]([CH3:36])[C:19](=[O:21])/[CH:18]=[CH:17]/[C:12]2[CH:13]=[N:14][C:15]3[NH:16][C:7](=[O:6])[CH2:8][CH2:9][C:10]=3[CH:11]=2)=[CH:26]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 221390051-(2-hydroxyethyl)-3-(methylaminomethyl)-1H-indoleHCID 66905305(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic Acid Hydrochloride

Product 1

HCID 66780748(E)-N-[1-(2-hydroxyethyl)-1H-indol-3-ylmethyl]-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamideYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (0.54 g, 2.80 mmole) was added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride salt (0.71 g, 2.80 mmole), 1-(2-hydroxyethyl)-3-(methylaminomethyl)-1H-indole (0.52 g, 2.55 mmole), HOBt H2O (0.38 g., 2.80 mmole) and diisopropylethylamine (1.11 mL, 6.40 mmole) in DMF (25 mL) at RT. The reaction was stirred overnight then was concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over Na2SO4. Flash chromatography on silica gel (20% EtOH/EtOAc) gave title compound (0.28 g, 27%) as an off-white solid after drying in vacuo: MS (ES) m/e 405 (M+H)+.

Workup

  1. concentrationthen was concentrated in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-f11776ac9bdf4ab5a14ea8263ea80ca3
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

Loading…