Tri-o-tolylphosphine → Indole naphthyridinone 32

HRID 1297458Notes

Reaction equation

HRID 1297458 reaction equation
[CH3:1][N:2]([CH2:7][C:8]1[C:16]2[C:11](=[C:12]([CH3:17])[CH:13]=[CH:14][CH:15]=2)[N:10]([CH3:18])[C:9]=1[CH3:19])[C:3](=[O:6])[CH:4]=[CH2:5].Br[C:21]1[CH:22]=[C:23]2[C:28](=[N:29][CH:30]=1)[NH:27][C:26](=[O:31])[CH2:25][CH2:24]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.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][N:2]([CH2:7][C:8]1[C:16]2[C:11](=[C:12]([CH3:17])[CH:13]=[CH:14][CH:15]=2)[N:10]([CH3:18])[C:9]=1[CH3:19])[C:3](=[O:6])/[CH:4]=[CH:5]/[C:21]1[CH:30]=[N:29][C:28]2[NH:27][C:26](=[O:31])[CH2:25][CH2:24][C:23]=2[CH:22]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 66905360N-methyl-N-(1,2,7-trimethyl-1H-indol-3-ylmethyl)acrylamide

Product 1

HCID 6539899Indole naphthyridinone 32Yield 25%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A mixture of N-methyl-N-(1,2,7-trimethyl-1H-indol-3-ylmethyl)acrylamide (256 mg, 1 mmole) and 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (227 mg, 1 mmole) in propionitrile (20 mL) was treated with DIEA (0.3 mL), Pd(OAc)2 (29 mg, 0.13 mmole), and tri-o-tolylphosphine (50 mg, 0.16 mmole). The reaction was heated at reflux under argon for 10 h, then was cooled to RT and filtered through supercel. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel to afford the title compound (100 mg, 25%) as an off-white solid: MS (ES) m/e 403.2 (M+H)+. Anal. Calcd for C24H26N4O2.2.75 H2O: C, 63.77; H, 7.02; N, 12.39. Found: C, 63.81; H, 7.25; N, 11.90.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux under argon for 10 h
  3. filtrationfiltered through supercel
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5a9a572030654a768243f859e0b146f6
Source dataset
uspto-grants-2007_07
Patent number
US07250424B2

Reaction notes

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