Tri-o-tolylphosphine → HCID 16662050, compound

HRID 1362281Notes

Reaction equation

HRID 1362281 reaction equation
[CH2:1]([O:5][C:6]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:7]=1[CH2:8][N:9]([CH3:14])[C:10](=[O:13])[CH:11]=[CH2:12])[CH:2]([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.Br[C:31]1[CH:32]=[C:33]2[C:38](=[N:39][CH:40]=1)[NH:37][C:36](=[O:41])[CH2:35][CH2:34]2.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:5][C:6]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:7]=1[CH2:8][N:9]([CH3:14])[C:10](=[O:13])/[CH:11]=[CH:12]/[C:31]1[CH:40]=[N:39][C:38]2[NH:37][C:36](=[O:41])[CH2:35][CH2:34][C:33]=2[CH:32]=1)[CH:2]([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 59277527N-(2-Isobutoxy-3-methoxybenzyl)-N-methylacrylamide

Product 1

HCID 16662050HCID 16662050, compoundYield 32.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-(2-isobutoxy-3-methoxybenzyl)-N-methyl-acrylamide (0.475 g, 1.71 mmol) in propionitrile (6 mL) and DMF (1.2 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.48 mL, 2.77 mmol) and 6-bromo-3,4-dihydro-1H-[1,8]naphthyridin-2-one (0.300 g, 1.32 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.029 g, 0.13 mmol) and P(o-tol)3 (0.080 g, 0.26 mmol) were then added and the mixture was deoxygenated with Ar for 20 min. The mixture was heated to reflux for 18 h. Upon cooling, a precipitate formed. The solids were collected by filtration and washed with water. Purification by column chromatography (silica gel, CH2Cl2/MeOH 9:1) gave an orange solid. The solid was dissolved in CH2Cl2 and the solution was diluted with hexanes. The resulting precipitate was collected by filtration, washed with Et2O (50 mL) and dried to yield the title compound (0.18 g, 32%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.66-10.64 (m, 1H), 8.36-8.32 (m, 1H), 8.09-8.00 (m, 1H), 7.53-7.47 (m, 1H), 7.27-7.20 (m, 1H), 7.04-7.96 (m, 2H), 6.66-6.60 (m, 1H), 4.79-4.64 (m, 2H), 3.79 (s, 3H), 3.72-3.67 (m, 2H), 3.10-2.85 (m, 5H), 2.56-2.49 (m, 2H), 2.03-1.97 (m, 1H), 1.00-0.97 (m, 6H); MS (ESI) m/e 424 (M+H)+.

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe mixture was deoxygenated with Ar for 20 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 18 h
  5. temperatureUpon cooling
  6. customa precipitate formed
  7. filtrationThe solids were collected by filtration
  8. washwashed with water
  9. customPurification by column chromatography (silica gel, CH2Cl2/MeOH 9:1)
  10. customgave an orange solid
  11. filtrationThe resulting precipitate was collected by filtration
  12. washwashed with Et2O (50 mL)
  13. customdried

Sources & evidence

ORD record
ord-08d202a92a3444a3992e197fe2eed76a
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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