Reaction #680036

Reaction equation

201a

5-Bromo-3-(imidazo[1,2-a]pyridin-7-ylamino)-1-methylpyrazin-2(1H)-one

{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

{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

acetonitrile

→

201b

Yield 34.0%

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

Yield 34.0%

Conditions

Workup

1. 1
   OtherA 25-mL single-neck round-bottomed flask equipped with a reflux condenser
2. 2
   OtherThe system was evacuated
3. 3
   workup.ADDITIONrefilled with N2
4. 4
   TemperatureIt was then cooled to room temperature
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 20:1 dichloromethane/methanol

Procedure

A 25-mL single-neck round-bottomed flask equipped with a reflux condenser was charged with 201a (64 mg, 0.20 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 199e (160 mg, 0.40 mmol), Pd(dppf)Cl2 (10 mg, 0.012 mmol), K3PO4 (100 mg, 0.39 mmol), NaOAc.3H2O (60 mg, 0.44 mmol), water (6 drops), and acetonitrile (5 mL). The system was evacuated and refilled with N2. The reaction mixture was stirred at 100° C. for 2 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 20:1 dichloromethane/methanol to afford 201b (40 mg, 34%) as a yellow brown solid. MS-ESI: [M+H]+ 593.2.

Source