Tri-o-tolylphosphine → (E)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(2-oxo-1,4-dihydro-2H-pyrido[2,3-d]-1,3-oxazin-6yl)acrylamide

HRID 1921065Notes

Reaction equation

HRID 1921065 reaction equation
[CH3:1][N:2]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])[CH:4]=[CH2:5].Br[C:19]1[CH:29]=[N:28][C:22]2[NH:23][C:24](=[O:27])[O:25][CH2:26][C:21]=2[CH:20]=1.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]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])/[CH:4]=[CH:5]/[C:19]1[CH:29]=[N:28][C:22]2[NH:23][C:24](=[O:27])[O:25][CH2:26][C:21]=2[CH:20]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 159259906-bromo-1H,2H,4H-pyrido(2,3-d)(1,3)oxazin-2-oneHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamide

Product 1

HCID 9821027(E)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(2-oxo-1,4-dihydro-2H-pyrido[2,3-d]-1,3-oxazin-6yl)acrylamideYield 55.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

To a stirred solution of N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (1.19 g, 5.2 mmole) in propionitrile (50 mL) was added 6-bromo-2-oxo-1,4-dihydro-2H-pyrido[2,3-d]-1,3-oxazine (1.1 g, 4.9 mmole), DIEA (1.75 mL, 10 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. The residue was taken up in CHCl3 and the solution was filtered through a pad of silica gel (3% methanol/CHCl3). The filtrate was concentrated and the residue was triturated with ethyl acetate, collected by suction filtration, and dried under vacuum gave the title compound (1.02 g, 55%) as an off-white solid: LCMS (ES) m/e 377 4 (M+H)+.

Workup

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 16 hr
  4. concentrationconcentrated under vacuum
  5. filtrationthe solution was filtered through a pad of silica gel (3% methanol/CHCl3)
  6. concentrationThe filtrate was concentrated
  7. customthe residue was triturated with ethyl acetate
  8. filtrationcollected by suction filtration
  9. customdried under vacuum

Sources & evidence

ORD record
ord-1b985aaefdb54dfb9e07d7e422b1a7cf
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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