Reaction #156411

Reaction equation

(rac)-6-Chloro-3-[1-(3-methyl-3H-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine

1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3 ,2]dioxaborolan-2-yl)-1H-pyrazole

→

title compound

(rac)-3-[1-(3-Methyl-3H-benzoimidazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

Solvents

DME

Conditions

Workup

1. 1
   OtherThe mixture was purged with Argon for 5 min
2. 2
   workup.ADDITIONPd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added
3. 3
   Otherthe mixture was flushed with Argon
4. 4
   Otherbefore being sealed
5. 5
   workup.ADDITIONThe RM was diluted with EtOAc
6. 6
   Washwashed with water, brine
7. 7
   Dryingdried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Otherevaporated
10. 10
    OtherThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min)
11. 11
    workup.ADDITIONThe collected fractions containing product
12. 12
    Otherwere evaporated
13. 13
    Otherthe residue was dried under vacuum

Procedure

(rac)-6-Chloro-3-[1-(3-methyl-3H-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Stage 185.2, 525 mg, 1.381 mmol) was introduced in a microwave reactor together with 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3 ,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 667 mg, 2.071 mmol) and DME (9 mL). The mixture was purged with Argon for 5 min. Pd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added and the mixture was flushed with Argon before being sealed. It was then heated at 90° C. for 4,5 h. The RM was diluted with EtOAc and washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound as an oil (tR 2.39 min (conditions 8), MH+=472).

Source