Cesium carbonate → HCID 66742925, compound

HRID 1431081Notes

Reaction equation

HRID 1431081 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:21]=[CH:20][C:14]([C:15]([N:17]([CH3:19])[CH3:18])=[O:16])=[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+].[O-]S([O-])(=O)=O.[Na+].[Na+]>C(Cl)Cl.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.O1CCOCC1>[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:21]=[CH:20][C:14]([C:15](=[O:16])[N:17]([CH3:19])[CH3:18])=[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

9

Reactant 4

HCID 10796Cesium carbonateHCID 24436Sodium SulfateHCID 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 66742180HCID 66742180, compound

Product 1

HCID 66742925HCID 66742925, compoundYield 52.2%

Reagents, catalysts & solvents 4

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

In a 250 mL round-bottomed flask, 6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)-N,N-dimethylnicotinamide (1.053 g, 3.42 mmol), 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 (2.2 g, 4.45 mmol) and Cs2CO3 (3.34 g, 10.3 mmol) were combined with dioxane (20 ml) and water (2.00 ml) to give a dark brown suspension. The suspension was purged with argon and PdCl2(DPPF) (83.8 mg, 103 μmol) was added. The reaction mixture was heated to 85° C. and stirred for 3 h. Cooled to 25° C. and diluted with DCM. Na2SO4 was added and the mixture was filtered through celite. The filter cake was washed with DCM until clear and the brown filtrate was conc. in vacuo. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 5% MeOH in DCM). The product was isolated impure and repurified by flash chromatography (silica gel, 220 g, 100% EtOAc) to afford 1.1412 g (52%) of the title compound as a cream colored solid. (M+H)+=640 m/e.

Workup

  1. customto give a dark brown suspension
  2. additionwas added
  3. temperatureCooled to 25° C.
  4. filtrationthe mixture was filtered through celite
  5. washThe filter cake was washed with DCM until clear and the brown filtrate
  6. customThe crude material was purified by flash chromatography (silica gel, 220 g, 0% to 5% MeOH in DCM)
  7. customThe product was isolated impure
  8. customrepurified by flash chromatography (silica gel, 220 g, 100% EtOAc)

Sources & evidence

ORD record
ord-9ff662fecf9f49b0b6a4000505128267
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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