Reaction #607479

Reaction equation

101a

N-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)cyclobutanecarboxamide

{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

NaOAc

→

101b

Yield 56.0%

[4-(5-cyclobutaneamido-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 56.0%

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 dichloromethane/methanol

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 101a (230 mg, 0.80 mmol), {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 (320 mg, 0.80 mmol), Pd(dppf)Cl2 (42 mg, 0.050 mmol), NaOAc (82 mg, 1.0 mmol), K3PO4.3H2O (266 mg, 1.0 mmol), water (5 drops) and acetonitrile (6 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 1 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 dichloromethane/methanol to afford 101b (200 mg, 56%) as a brown solid. MS-ESI: [M+H]+ 558.3

Source