Cesium carbonate → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

HRID 449604Notes

Reaction equation

HRID 449604 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH2:20][CH3:21])(=[O:19])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:22]([O:25][CH2:26][C:27]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[CH:29][C:28]=1[N:42]1[N:51]=[CH:50][C:49]2[C:44](=[C:45]([F:56])[CH:46]=[C:47]([C:52]([CH3:55])([CH3:54])[CH3:53])[CH:48]=2)[C:43]1=[O:57])(=[O:24])[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].O>[C:52]([C:47]1[CH:48]=[C:49]2[C:44](=[C:45]([F:56])[CH:46]=1)[C:43](=[O:57])[N:42]([C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([S:17]([CH2:20][CH3:21])(=[O:19])=[O:18])=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:27]=1[CH2:26][O:25][C:22](=[O:24])[CH3:23])[N:51]=[CH:50]2)([CH3:53])([CH3:54])[CH3:55]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 667424096-chloro-4-(5-(ethylsulfonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

Product 1

HCID 667427742-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

In a 250 mL round-bottomed flask, 6-chloro-4-(5-(ethylsulfonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (79 mg, 240 μmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (154 mg, 312 μmol) and Cs2CO3 (235 mg, 721 μmol) were combined with dioxane (10 ml) and water (1 ml) to give a light yellow suspension. The mixture was evacuated and filled with argon. PdCl2(DPPF) (9.81 mg, 12.0 μmol) was added, the reaction mixture was purged with argon and heated to 85° C. for 60 h. The reaction mixture was diluted with DCM and filtered through celite. The filter cake was washed with DCM until clear. The filtrate was dried over Na2SO4 and concentrated in vacuo to give a dark brown oil. The brown oil was used crude in the subsequent reaction. (M−H)+=659 m/e.

Workup

  1. customto give a light yellow suspension
  2. customThe mixture was evacuated
  3. additionfilled with argon
  4. customthe reaction mixture was purged with argon
  5. additionThe reaction mixture was diluted with DCM
  6. filtrationfiltered through celite
  7. washThe filter cake was washed with DCM until clear
  8. dry with materialThe filtrate was dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customto give a dark brown oil
  11. customin the subsequent reaction

Sources & evidence

ORD record
ord-13d6c81c02054390a931a6d1145f5b24
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

Loading…