2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → 1-(1-(5-Ethylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407893Notes

Reaction equation

HRID 407893 reaction equation
CC([O-])(C)C.[Na+].C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.Cl[C:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH3:38])=[CH:33][N:32]=1.[F:39][C:40]1[CH:45]=[C:44]([S:46]([CH3:49])(=[O:48])=[O:47])[CH:43]=[CH:42][C:41]=1[NH:50][C@H:51]1[CH2:55][CH2:54][N:53]([CH:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)[C:52]1=[O:62]>CCOC(C)=O.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].C1(C)C=CC=CC=1>[CH2:37]([C:34]1[CH:35]=[CH:36][C:31]([N:59]2[CH2:58][CH2:57][CH:56]([N:53]3[CH2:54][CH2:55][CH:51]([NH:50][C:41]4[CH:42]=[CH:43][C:44]([S:46]([CH3:49])(=[O:47])=[O:48])=[CH:45][C:40]=4[F:39])[C:52]3=[O:62])[CH2:61][CH2:60]2)=[N:32][CH:33]=1)[CH3:38]

Participants

8

Reactant 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 111263632-Chloro-5-ethylpyridineHCID 23676156Sodium t-butoxideHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

Product 1

HCID 674697791-(1-(5-Ethylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 54.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a nitrogen purged vessel was added Pd2 dba3 (0.0386 g, 0.0422 mmol), NaOtBu (0.169 g, 1.76 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (0.0600 mL, 0.169 mmol), 2-chloro-5-ethylpyridine (0.100 g, 0.703 mmol) and (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.300 g, 0.844 mmol). Toluene (4 mL, purged with nitrogen) was added and the reaction was heated at 100° C. overnight. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed with water. The organics were dried over Na2SO4, concentrated and purified on silica eluting with 100% EtOAc to give 1-(1-(5-ethylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.177 g, 54% yield) as white solids. Mass spectrum (apci) m/z=461.3 (M+H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. washwashed with water
  3. dry with materialThe organics were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified on silica eluting with 100% EtOAc

Sources & evidence

ORD record
ord-17c084d2fc3a4338bcf8cc1dc42b93ca
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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