Reaction #680090

Reaction equation

221a

3-[(6-aminopyridin-2-yl)amino]-5-bromo-1-methyl-1,2-dihydropyridin-2-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

→

221b

Yield 31.0%

(4-{5-[(6-Aminopyridin-2-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-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 31.0%

Solvents

acetonitrile

Conditions

Workup

1. 1
   OtherA 25-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 30:1 ethyl acetate/methanol

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 221a (354 mg, 1.2 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 (1.20 g, 3.0 mmol), Pd(dppf)Cl2 (99 mg, 0.12 mmol), potassium acetate (235 mg, 2.4 mmol), K3PO4 (532 mg, 2.4 mmol), acetonitrile (12 mL), and water (10 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 30:1 ethyl acetate/methanol to afford 221b (210 mg, 31%) as a yellow solid. MS-ESI: [M+H]+ 568.3

Source