Ethyl Acrylate → (E)-Ethyl 3-(8-cyclopentyl-4-methyl-2-(methylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)acrylate

HRID 641639Notes

Reaction equation

HRID 641639 reaction equation
Br[C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=1.[C:21]([O:25][CH2:26][CH3:27])(=[O:24])[CH:22]=[CH2:23].C1(N(C)C2CCCCC2)CCCCC1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[Cl-].[Li+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:16]1([N:13]2[C:5]3[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=3[CH:3]=[C:2](/[CH:23]=[CH:22]/[C:21]([O:25][CH2:26][CH3:27])=[O:24])[C:14]2=[O:15])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 8821Ethyl AcrylateHCID 24210N-Methyl dicyclohexylamineHCID 433294Lithium ChlorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 592588576-Bromo-8-cyclopentyl-4-methyl-2-methylamino-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 59258875(E)-Ethyl 3-(8-cyclopentyl-4-methyl-2-(methylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)acrylateYield 90%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

6-bromo-8-cyclopentyl-4-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (375 mg, 1.1 mmole), ethyl acrylate (442 mg, 4.42 mmole), N-cyclohexyl-N-methylcyclohexanamine (280 mg, 1.43 mmole), tri-tert-butylphosphonium tetrafluoroborate (9.61 mg, 0.03 mmole), lithium chloride (42.4 mg, 3.3 mmole), tris(dibenzylideneacetone)dipalladium(0)) (30.3 mg, 0.03 mmole) and 1,4-dioxane (10 ml) were added to a reaction vial equipped with a stir bar. The reaction vial was flushed with nitrogen, capped, and heated at 75° C. for 75 min. The reaction mixture was cooled to ambient temperature, filtered through Celite™, and washed with ethyl acetate. The filtrate and washing were combined, and the volatiles were removed under reduced pressure to a yellow solid residue. This solid residue was crystallized from boiling heptane:ethyl acetate (50 ml:50 ml). Upon cooling to ambient temperature, needle-liked yellow crystals formed and collected by filtration to give the title compound as a beta-trans isomer (356 mg, 90% yield).

Workup

  1. customvial equipped with a stir bar
  2. customThe reaction
  3. customvial was flushed with nitrogen
  4. customcapped
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. filtrationfiltered through Celite™
  7. washwashed with ethyl acetate
  8. washThe filtrate and washing
  9. customthe volatiles were removed under reduced pressure to a yellow solid residue
  10. customThis solid residue was crystallized
  11. temperatureUpon cooling to ambient temperature
  12. customneedle-liked yellow crystals formed
  13. filtrationcollected by filtration

Sources & evidence

ORD record
ord-6e6f6d6822934f6abf5c06b3d5db48d9
Source dataset
uspto-grants-2010_04
Patent number
US07696213B2

Reaction notes

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