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

HRID 2112722Notes

Reaction equation

HRID 2112722 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH2:12][N:13]([CH3:18])[C:14](=[O:17])[CH:15]=[CH2:16].Br[C:20]1[CH:21]=[C:22]2[C:27](=[N:28][CH:29]=1)[NH:26][C:25](=[O:30])[CH2:24][CH2:23]2.CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH2:12][N:13]([CH3:18])[C:14](=[O:17])/[CH:15]=[CH:16]/[C:20]1[CH:29]=[N:28][C:27]2[NH:26][C:25](=[O:30])[CH2:24][CH2:23][C:22]=2[CH:21]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 22593810N-(1,3-Dimethyl-1H-indol-2-ylmethyl)-N-methylacrylamide

Product 1

HCID 23658030(E)-N-(1,3-Dimethyl-1H-indol-2-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro[1,8]naphthyridin-3-yl)acrylamideYield 59.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

To a stirred solution of N-(1,3-dimethyl-1H-indol-2-ylmethyl)-N-methylacrylamide (1.7 g, 7 mmole) in propionitrile (50 mL) was added 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (1.16 g, 5.1 mmole), DIEA (1.8 mL, 10.3 mmole), palladium(II) acetate (112 mg, 0.5 mmole), and tri-o-tolylphosphine (304 mg, 1.0 mmole). The reaction was purged with argon and heated at reflux for 16 hr, then was cooled to RT and concentrated under vacuum. Purification by flash chromatography on silica gel (5% methanol/CHCl3), trituration with ethyl acetate, filtration, and drying under vacuum gave the title compound (1.17 g, 59%) as an off-white solid: LCMS (ES) m/e 389.2 (M+H)+.

Workup

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 16 hr
  4. concentrationconcentrated under vacuum
  5. customPurification by flash chromatography on silica gel (5% methanol/CHCl3), trituration
  6. filtrationwith ethyl acetate, filtration
  7. customdrying under vacuum

Sources & evidence

ORD record
ord-6ba1c61cc23849fcbd3af3b8d7f2b8f4
Source dataset
uspto-grants-2009_04
Patent number
US07524843B2

Reaction notes

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