Toluene → 1-(1-(5-Ethyl-3-methylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407899Notes

Reaction equation

HRID 407899 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:8]1[C:13]([CH3:14])=[CH:12][C:11]([CH2:15][CH3:16])=[CH:10][N:9]=1.[F:17][C:18]1[CH:23]=[C:22]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:21]=[CH:20][C:19]=1[NH:28][C@H:29]1[CH2:33][CH2:32][N:31]([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[C:30]1=[O:40].C1(C)C=CC=CC=1>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]>[CH2:15]([C:11]1[CH:12]=[C:13]([CH3:14])[C:8]([N:37]2[CH2:36][CH2:35][CH:34]([N:31]3[CH2:32][CH2:33][CH:29]([NH:28][C:19]4[CH:20]=[CH:21][C:22]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:23][C:18]=4[F:17])[C:30]3=[O:40])[CH2:39][CH2:38]2)=[N:9][CH:10]=1)[CH3:16]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-oneHCID 866880852-Chloro-5-ethyl-3-methylpyridine

Product 1

HCID 674697771-(1-(5-Ethyl-3-methylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 23.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a nitrogen purged reaction vessel was added Pd2 dba3 (0.0129 g, 0.0141 mmol), Cs2CO3 (0.229 g, 0.703 mmol), Binap-rac (0.035 g, 0.0563 mmol), 2-chloro-5-ethyl-3-methylpyridine (0.037 g, 0.234 mmol) and (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.100 g, 0.281 mmol). Toluene (3 mL, purged with nitrogen) was added and the reaction was heated at 110° C. overnight. The reaction was cooled to ambient temperature, diluted with EtOAc and washed with water. The combined organic layers were dried over Na2SO4 and purified by preparative HPLC (Parallex Flex) to give 1-(1-(5-ethyl-3-methylpyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.026 g, 23% yield) as white solids. Mass spectrum (apci) m/z=475.3 (M+H).

Workup

  1. customTo a nitrogen purged
  2. customreaction vessel
  3. temperatureThe reaction was cooled to ambient temperature
  4. washwashed with water
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. custompurified by preparative HPLC (Parallex Flex)

Sources & evidence

ORD record
ord-99f1aaa3f9ed4348b65bd954da99ef41
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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