Nitrogen → tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate

HRID 524885Notes

Reaction equation

HRID 524885 reaction equation
[CH3:1][C:2]1([CH3:42])C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:3]1=2.[N:43]#N.Br[C:46]1[CH:47]=[N:48][CH:49]=[C:50]([F:67])[C:51]=1[N:52]1[CH2:57][CH2:56][CH:55]([C:58]([N:60]2[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]2)=[O:59])[CH2:54][CH2:53]1.[C:68]([O-:71])([O-])=[O:69].[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]>[F:67][C:50]1[C:51]([N:52]2[CH2:57][CH2:56][CH:55]([C:58]([N:60]3[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]3)=[O:59])[CH2:54][CH2:53]2)=[C:46]([NH:43][C:68](=[O:69])[O:71][C:2]([CH3:42])([CH3:3])[CH3:1])[CH:47]=[N:48][CH:49]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86720941(1-(3-Bromo-5-fluoropyridin-4-yl)piperidin-4-yl)(4-methylpiperazin-1-yl)methanone

Product 1

HCID 86720942tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

In an alternative method to Step 3, above, Tris(dibenzylideneacetone)dipalladium (1.189 g, 1.298 mmol) and xantphos (1.502 g, 2.596 mmol) were added to a degassed (3×vacuum/N2 cycles) mixture of [1-(3-bromo-5-fluoro-4-pyridyl)-4-piperidyl]-(4-methylpiperazin-1-yl)methanone 19 (10 g, 25.96 mmol) and Cs2CO3 (16.92 g, 51.92 mmol) in dioxane (150 mL) under N2. The mixture was stirred at 100° C. overnight. The reaction was cooled to ambient temperature and the precipitate was filtered off and washed with EtOAc (50 mL). The filtrate was partitioned between EtOAc and water. The combined organic layers were washed with water, brine, dried (MgSO4) and concentrated in vacuo to leave tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate as a red solid that was used in next step without further purification. MS (ES+) 422.2.

Workup

  1. customa degassed
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationthe precipitate was filtered off
  4. washwashed with EtOAc (50 mL)
  5. customThe filtrate was partitioned between EtOAc and water
  6. washThe combined organic layers were washed with water, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-41d9d89506894c529df598cfdeab7091
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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