Tri-o-tolylphosphine → (E)-N-(1-benzyl-1H-indol-3-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

HRID 18319Notes

Reaction equation

HRID 18319 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH2:13]([N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([CH2:29][N:30]([CH3:35])[C:31](=[O:34])[CH:32]=[CH2:33])=[CH:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:13]([N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([CH2:29][N:30]([CH3:35])[C:31](=[O:34])/[CH:32]=[CH:33]/[C:2]2[CH:11]=[N:10][C:9]3[NH:8][C:7](=[O:12])[CH2:6][CH2:5][C:4]=3[CH:3]=2)=[CH:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 66905256N-(1-benzyl-1H-indol-3-ylmethyl)-N-methyl-acrylamide

Product 1

HCID 10343753(E)-N-(1-benzyl-1H-indol-3-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamideYield 35%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A solution of 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (1.05 g, 4.60 mmole), N-(1-benzyl-1H-indol-3-ylmethyl)-N-methyl-acrylamide (1.40 g, 4.60 mmole), Pd(OAc)2 (0.10 g, 0.46 mmole), tri-ortho-tolylphosphine (0.28 g, 0.92 mmole) and diisopropylethylamine (1.20 mL 6.90 mmole) in propionitrile (75 mL) was deoxygenated, then was and heated to reflux under a N2 overnight. The dark mixture was filtered through a pad of Celite®, and the filter pad was rinsed with acetonitrile (300 mL). The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (5% MeOH/CHCl3). The title compound (0.70 g. 35%) was obtained as a light yellow solid after drying in vacuo: MS (ES) m/e 451 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux under a N2 overnight
  3. filtrationThe dark mixture was filtered through a pad of Celite®
  4. washthe filter pad was rinsed with acetonitrile (300 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by flash chromatography on silica gel (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-0a0906d402c04503aae1069b0211255e
Source dataset
uspto-grants-2010_06
Patent number
US07741339B2

Reaction notes

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