Potassium Carbonate → (S)-1-(1-(5-ethylpyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407888Notes

Reaction equation

HRID 407888 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([NH:19][C:20]4[CH:25]=[C:24]([CH3:26])[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:22][C:21]=4[F:31])[C:15]3=[O:32])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH2:39]([Zn]CC)[CH3:40]>C1COCC1.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]>[CH2:39]([C:2]1[N:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([NH:19][C:20]4[CH:25]=[C:24]([CH3:26])[C:23]([S:27]([CH3:30])(=[O:28])=[O:29])=[CH:22][C:21]=4[F:31])[C:15]3=[O:32])[CH2:12][CH2:13]2)=[N:6][CH:7]=1)[CH3:40]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 54671274(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneHCID 178418750HCID 178418750, compound

Product 1

HCID 54671275(S)-1-(1-(5-ethylpyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 55.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

(S)-1-(1-(5-Chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (Example 1; 320 mg, 0.664 mmol) was dissolved in THF (6 mL) and K2CO3 (275 mg, 1.99 mmol) and PdCl2(dppf)*CH2Cl2 (54.2 mg, 0.0664 mmol) were added and purged with nitrogen. Diethylzinc (1 M in THF; 797 μL, 0.797 mmol) was added and the reaction heated to 60° C. for 1 hour. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified over silica gel (100% EtOAc) to afford (S)-1-(1-(5-ethylpyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (175 mg, 0.368 mmol, 55.4% yield) as a tan solid. Mass spectrum (apci) m/z=476.3 (M+H).

Workup

  1. custompurged with nitrogen
  2. temperatureThe reaction was cooled to ambient temperature
  3. custompartitioned between water and EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-094740c25f8c4ecfa08db7060beabed8
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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