Water → (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(ethylsulfonyl)-2-fluorophenylamino)pyrrolidin-2-one

HRID 407905Notes

Reaction equation

HRID 407905 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[N:18]=[CH:17][C:16]([CH2:19][CH3:20])=[CH:15][N:14]=3)[CH2:9][CH2:8]2)[C:3]1=[O:21].F[C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])=[CH:25][C:24]=1[F:34].C([O-])([O-])=O.[Na+].[Na+].O>CS(C)=O>[CH2:19]([C:16]1[CH:15]=[N:14][C:13]([N:10]2[CH2:11][CH2:12][CH:7]([N:4]3[CH2:5][CH2:6][C@H:2]([NH:1][C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])=[CH:25][C:24]=4[F:34])[C:3]3=[O:21])[CH2:8][CH2:9]2)=[N:18][CH:17]=1)[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 265973661,2-Difluoro-4-ethylsulfonylbenzeneHCID 67469717(S)-3-amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one

Product 1

HCID 54670242(S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(ethylsulfonyl)-2-fluorophenylamino)pyrrolidin-2-oneYield 31.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of ((S)-3-amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (100 mg, 0.35 mmol), 1,2-difluoro-4-(ethylsulfonyl)benzene (0.2 g, 1.0 mmol), and Na2CO3 (110 mg, 1.0 mmol) in DMSO (2 mL) was stirred at 130° C. for 18 hours. The reaction mixture was poured into water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine and dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified over silica gel (10% methanol in EtOAc) to yield (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(ethylsulfonyl)-2-fluorophenylamino)pyrrolidin-2-one (50 mg, 0.11 mmol, 30%). Mass spectrum (apci) m/z=476.3 (M+H).

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified over silica gel (10% methanol in EtOAc)

Sources & evidence

ORD record
ord-93ade18837fe4e5b97e5f92579ea7dde
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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