Cesium carbonate → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-hydroxy-4-methylpiperidine-1-carbonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

HRID 1431084Notes

Reaction equation

HRID 1431084 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[CH2:24][CH2:23][C:22]([OH:26])([CH3:25])[CH2:21][CH2:20]3)=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][CH:35]=[CH:34][C:33]=1[N:47]1[N:56]=[CH:55][C:54]2[C:49](=[C:50]([F:61])[CH:51]=[C:52]([C:57]([CH3:60])([CH3:59])[CH3:58])[CH:53]=2)[C:48]1=[O:62])(=[O:29])[CH3:28].C([O-])([O-])=O.[Cs+].[Cs+].[O-]S([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.O.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]>[C:57]([C:52]1[CH:53]=[C:54]2[C:49](=[C:50]([F:61])[CH:51]=1)[C:48](=[O:62])[N:47]([C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([C:17]([N:19]5[CH2:24][CH2:23][C:22]([OH:26])([CH3:25])[CH2:21][CH2:20]5)=[O:18])=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:32]=1[CH2:31][O:30][C:27](=[O:29])[CH3:28])[N:56]=[CH:55]2)([CH3:58])([CH3:59])[CH3:60]

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 667423526-chloro-4-(5-(4-hydroxy-4-methylpiperidine-1-carbonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

Product 1

HCID 667425262-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-hydroxy-4-methylpiperidine-1-carbonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Reagents, catalysts & solvents 4

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

Conditions

Temperature
125 °C

Procedure

To a 10 mL microwave vial was added 6-chloro-4-(5-(4-hydroxy-4-methylpiperidine-1-carbonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (33 mg, 87.3 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 (56.1 mg, 114 μmol) and Cs2CO3 (99.6 mg, 306 μmol) in dioxane (5 ml) and water (0.5 ml). The yellow suspension was purged with argon and PdCl2(DPPF) (7.13 mg, 8.73 μmol) was added. The vial was capped and heated in the microwave at 125° C. for 30 min. The reaction was 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 yellow filtrate was conc. in vacuo to afford the title compound as a brown solid in quantitative yield. (M−H)+=708 m/e.

Workup

  1. additionwas added
  2. customThe vial was capped
  3. temperatureThe reaction was cooled to 25° C.
  4. filtrationthe mixture was filtered through celite
  5. washThe filter cake was washed with DCM until clear and the yellow filtrate

Sources & evidence

ORD record
ord-ddb9ccfe0c914f75b6d8985540722510
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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