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

HRID 1690420Notes

Reaction equation

HRID 1690420 reaction equation
Br[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1.[CH3:17][C:18]1[NH:19][C:20]2[C:25]([C:26]=1[CH2:27][N:28]([CH3:33])[C:29](=[O:32])[CH:30]=[CH2:31])=[CH:24][CH:23]=[CH:22][CH:21]=2.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]>[CH3:33][N:28]([CH2:27][C:26]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][C:18]=1[CH3:17])[C:29](=[O:32])/[CH:30]=[CH:31]/[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 221390516-bromo-3-(2-methoxyethyl)-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-oneHCID 22139057N-(2-methyl-1H-indol-3-ylmethyl)-N-methylacrylamide

Product 1

HCID 11743597(E)-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-[3-(2-methoxyethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl]acrylamideYield 36%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A solution of 6-bromo-3-(2-methoxyethyl)-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-one (0.86 g, 3.00 mmole), N-(2-methyl-1H-indol-3-ylmethyl)-N-methylacrylamide (see Example 1 (a), 0.68 g, 3.00 mmole), Pd(OAc)2 (0.07 g, 0.30 mmole), tri-ortho-tolylphosphine (0.18 g, 0.60 mmole) and diisopropylethylamine (1.31 mL, 7.50 mmole) in propionitrile (50 mL) was deoxygenated, then was heated at reflux under N2 overnight. The dark mixture was filtered through a pad of Celite®, and the filter pad was rinsed with acetonitrile (250 mL). The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (10% EtOAc/EtOH). The title compound (0.46 g, 36%) was obtained as a light yellow solid after drying in vacuo: MS (ES) m/e 434 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under N2 overnight
  3. filtrationThe dark mixture was filtered through a pad of Celite®
  4. washthe filter pad was rinsed with acetonitrile (250 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by flash chromatography on silica gel (10% EtOAc/EtOH)

Sources & evidence

ORD record
ord-34645134f8b241d9958f0b47dd607551
Source dataset
uspto-grants-2012_04
Patent number
US08153652B2

Reaction notes

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