Cesium carbonate → HCID 24901162, compound

HRID 557533Notes

Reaction equation

HRID 557533 reaction equation
[N:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[C:15]1[C:20](=[O:21])[N:19]([CH3:22])[CH:18]=[C:17]([C:23]2[C:24]([CH3:42])=[C:25]([NH:29][C:30](=[O:41])[C:31]3[CH:36]=[CH:35][C:34]([C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:33][CH:32]=3)[CH:26]=[CH:27][CH:28]=2)[CH:16]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:37]([C:34]1[CH:35]=[CH:36][C:31]([C:30]([NH:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([C:17]3[CH:16]=[C:15]([NH:13][C:10]4[CH:9]=[CH:8][C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[CH:12][N:11]=4)[C:20](=[O:21])[N:19]([CH3:22])[CH:18]=3)[C:24]=2[CH3:42])=[O:41])=[CH:32][CH:33]=1)([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 113673465-Morpholinopyridin-2-amineHCID 59740593HCID 59740593, compound

Product 1

HCID 24901162HCID 24901162, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with 5-morpholin-4-yl-pyridin-2-ylamine (0.065 g, 0.36 mmol), N-[3-(5-bromo-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide (13) (0.16 g, 0.35 mmol), Pd2(dba)3 (0.030 g, 0.030 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.030 g, 0.050 mmol), and Cs2CO3 (0.22 g, 0.66 mmol) in dioxane (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (10 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1), to afford 0.080 g (41%) of 4-tert-butyl-N-{2-methyl-3-[1-methyl-5-(5-morpholin-4-yl-pyridin-2-ylamino)-6-oxo-1,6-dihydro-pyridin-3-yl]-phenyl}-benzamide (8) as a solid; LCMS m/z 552.2342 (M+).

Workup

  1. customA 48-mL sealed tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the mixture was degassed for 15 min.
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. additionpoured into H2O (10 mL)
  6. additionTo this was added dichloromethane (10 mL)
  7. customthe layers were separated
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1)

Sources & evidence

ORD record
ord-d089430a69a84563a1d63709797a931f
Source dataset
uspto-grants-2011_11
Patent number
US08058446B2

Reaction notes

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