Cesium carbonate → 2-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde

HRID 600369Notes

Reaction equation

HRID 600369 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=[O:32].Br[C:34]1[CH:41]=[CH:40][CH:39]=[C:38]([N:42]2[N:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[C:47]([C:52]([CH3:55])([CH3:54])[CH3:53])[CH:48]=3)[C:43]2=[O:56])[C:35]=1[CH:36]=[O:37].O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:52]([C:47]1[CH:48]=[C:49]2[C:44](=[CH:45][CH:46]=1)[C:43](=[O:56])[N:42]([C:38]1[CH:39]=[CH:40][CH:41]=[C:34]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[O:25])=[CH:20][N:19]=4)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=3)[C:35]=1[CH:36]=[O:37])[N:51]=[CH:50]2)([CH3:55])([CH3:53])[CH3:54]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 580161852-bromo-6-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)benzaldehydeHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one

Product 1

HCID 580161872-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehydeYield 69.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

149 mg (0.338 mmol) of 1-methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyridin-2-one and 116 mg (0.301 mmol) of 2-bromo-6-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-benzaldehyde were weighed into a 4 mL reaction vial fitted with a stir bar and septum cap. Added 2.5 mL of dioxane. Added 0.33 mL (0.92 mmol) of an 0.91 g/mL solution of cesium carbonate in water. The mixture was sparged with nitrogen for 10 min. Added 13 mg (0.016 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride 1:1 complex with dichloromethane. The mixture was sparged with nitrogen for 5 min. Sealed the vial with a cap and stirred at 95° for 90 min. Cooled the reaction to room temperature, diluted with 15 mL CH2Cl2 and dried over Na2SO4. Filtered through a 0.45 μM syringe filter and removed the solvent on rotavap. Purified the crude by flash chromatography on silica gel to obtain 129 mg of the title compound as a light yellow solid. MS (ESI) 619 (M+H)+.

Workup

  1. customvial fitted with a stir bar
  2. customseptum cap
  3. customThe mixture was sparged with nitrogen for 10 min
  4. customThe mixture was sparged with nitrogen for 5 min
  5. customSealed the vial with
  6. customa cap
  7. temperatureCooled
  8. customthe reaction to room temperature
  9. dry with materialdried over Na2SO4
  10. filtrationFiltered through a 0.45 μM syringe
  11. filtrationfilter
  12. customremoved the solvent on rotavap
  13. customPurified the crude by flash chromatography on silica gel

Sources & evidence

ORD record
ord-03fa55f6b1504901ae56d7c25ff7b205
Source dataset
uspto-grants-2011_03
Patent number
US07902194B2

Reaction notes

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