Reaction #680110

Reaction equation

water

229b

5-Bromo-3-(2-ethylpyrimidin-4-ylamino)-1-methylpyridin-2(1H)-one

(3-(acetoxymethyl)-2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)pyridin-4-yl)boronic acid

{3-[(Acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic Acid

K3PO4

→

229c

Yield 55.6%

(2′-(7,7-Dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta-[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-5-((2-ethylpyrimidin-4-yl)amino)-1-methyl-6-oxo-1,6-dihydro-[3,4′-bipyridin]-3′-yl)methyl Acetate

Yield 55.6%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherA 100-mL round-bottomed flask equipped with a reflux condenser
2. 2
   OtherAfter three cycles of vacuum/argon flush
3. 3
   Temperaturethe mixture was heated
4. 4
   Temperatureat reflux for 3 h
5. 5
   Filtrationfiltered
6. 6
   ConcentrationThe filtrate was concentrated under reduced pressure
7. 7
   Otherthe resulting residue was purified by silica-gel column chromatography
8. 8
   Washeluting with 60:1 dichloromethane/methanol

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 229b (277 mg, 0.90 mmol), (3-(acetoxymethyl)-2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)pyridin-4-yl)boronic acid 199e (358 mg, 0.90 mmol), Pd(dppf)Cl2 (74 mg, 0.090 mmol), K3PO4 (381 mg, 1.80 mmol), water (2 mL), and tetrahydrofuran (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at reflux for 3 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 60:1 dichloromethane/methanol to afford 229c as white solid (291 mg, 50%). MS-ESI: [M+H]+ 582.4

Source