Reaction #494984

Reaction equation

153b

1-Methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-ylboronic Acid

2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde

2-(6-tert-butyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)-4-chloronicotinaldehyde

K3PO4

sodium acetate

acetonitrile

→

153c

Yield 42.0%

2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde

Yield 42.0%

Solvents

water

Conditions

Workup

1. 1
   OtherA 25-mL round-bottomed flask equipped with a reflux condenser
2. 2
   OtherThe system was evacuated
3. 3
   workup.ADDITIONrefilled with N2
4. 4
   TemperatureThe mixture was cooled to room temperature
5. 5
   Filtrationfiltered
6. 6
   ConcentrationThe filtrate was concentrated under reduced pressure
7. 7
   Otherthe residue was purified on silica-gel column
8. 8
   Washeluting with 20:1 dichloromethane/methanol

Procedure

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 153b (200 mg, 0.66 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (240 mg, 0.66 mmol), PdCl2(dppf) (54 mg, 0.066 mmol), K3PO4 (250 mg, 1.2 mmol), sodium acetate (100 mg, 1.20 mmol), acetonitrile (10 mL), and water (0.5 mL). The system was evacuated and then refilled with N2. It was then heated at 100° C. for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 20:1 dichloromethane/methanol to afford 153c as a pale yellow solid (170 mg, 42%). MS-ESI: [M+H]+ 584.3.

Source