Reaction #162845

Reaction equation

N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

chloroform

trimethylsilylacetylene

→

N-{3-[3-cyclopropyl-5-(2-fluoro-4-trimethylsilanylethynylphenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

Yield 93.0%

Solvents

triethylamine

Conditions

Workup

1. 1
   ConcentrationThe mixture was concentrated under reduced pressure, activated carbon (435 mg) and methanol (435 ml)
2. 2
   workup.ADDITIONwere added to the residue
3. 3
   workup.STIRRINGthe mixture was stirred
4. 4
   Temperaturewith heating
5. 5
   Temperatureat reflux for 2 hrs
6. 6
   FiltrationActivated carbon was filtered off while it
7. 7
   Concentrationthe filtrate was concentrated under reduced pressure
8. 8
   OtherThe residue was purified by column chromatography (chloroform:acetone=10:1→4:1) and toluene-acetone [5:1 (volume ratio), 87 ml]
9. 9
   workup.ADDITIONwas added to the obtained crystals
10. 10
    workup.STIRRINGThe mixture was stirred at 80° C. for 1 hr
11. 11
    Temperatureto cool to room temperature
12. 12
    Filtrationthe crystals were collected by filtration
13. 13
    Otherdried

Procedure

Under a nitrogen atmosphere, to N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 59 (14.5 g) obtained in Example 4-1 were added chloroform (145 ml), trimethylsilylacetylene 60 (4.99 ml) and triethylamine (13.1 ml). Copper(I) iodide (22 mg) and bis(triphenylphosphine)palladium(II)chloride (83 mg) were added, and the mixture was stirred at room temperature for 20 hrs. The mixture was concentrated under reduced pressure, activated carbon (435 mg) and methanol (435 ml) were added to the residue, and the mixture was stirred with heating at reflux for 2 hrs. Activated carbon was filtered off while it was hot, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone=10:1→4:1) and toluene-acetone [5:1 (volume ratio), 87 ml] was added to the obtained crystals. The mixture was stirred at 80° C. for 1 hr. After allowing to cool to room temperature, the crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-trimethylsilanylethynylphenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 61 (12.9 g, yield 93%) as pale-yellow crystals.

Source