Reaction #680085

Reaction equation

219a

3-(3-Aminophenylamino)-5-bromo-1-methylpyrazin-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

potassium acetate

K3PO4

→

219b

Yield 38.5%

(4-{6-[(3-Aminophenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl)methyl Acetate

Yield 38.5%

Solvents

acetonitrile

Conditions

Workup

1. 1
   OtherA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. 2
   OtherAfter three cycles of vacuum/argon flush
3. 3
   FiltrationIt was then filtered
4. 4
   Otherthe filtrate was evaporated in vacuo
5. 5
   OtherThe residue was purified by silica-gel column chromatography
6. 6
   Washeluting with 20:1 ethyl acetate/methanol

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 219a (480 mg, 1.62 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 (1.61 g, 4.05 mmol), Pd(dppf)Cl2 (134 mg, 0.162 mmol), potassium acetate (318 mg, 3.24 mmol), K3PO4 (706 mg, 3.24 mmol), acetonitrile (20 mL), and water (8 drops). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 20:1 ethyl acetate/methanol to afford 219b (354 mg, 38%) as a yellow solid. MS-ESI: [M+H]+ 568.3

Source