Diisopropylethylamine → (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)pyrrolidin-2-one

HRID 407958Notes

Reaction equation

HRID 407958 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:27]=[C:26]([C:28]2[O:29][C:30]([CH3:33])=[N:31][N:32]=2)[CH:25]=[CH:24][C:10]=1[O:11][C@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[C:13]1=[O:23].[Cl:34][C:35]1[CH:40]=[N:39][C:38](Cl)=[CH:37][N:36]=1.C(N(C(C)C)C(C)C)C>CS(C)=O.O>[Cl:34][C:35]1[N:36]=[CH:37][C:38]([N:20]2[CH2:19][CH2:18][CH:17]([N:14]3[CH2:15][CH2:16][C@H:12]([O:11][C:10]4[CH:24]=[CH:25][C:26]([C:28]5[O:29][C:30]([CH3:33])=[N:31][N:32]=5)=[CH:27][C:9]=4[F:8])[C:13]3=[O:23])[CH2:22][CH2:21]2)=[N:39][CH:40]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 3362242,5-DichloropyrazineHCID 67469867(S)-3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-1-(piperidin-4-yl)pyrrolidin-2-one 2,2,2-trifluoroacetate

Product 1

HCID 86688104(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)pyrrolidin-2-oneYield 10.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

(S)-3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-1-(piperidin-4-yl)pyrrolidin-2-one 2,2,2-trifluoroacetate (150 mg, 0.316 mmol) was dissolved in DMSO (3 mL) and 2,5-dichloropyrazine (70.7 mg, 0.474 mmol) and N-ethyl-N-isopropylpropan-2-amine (138 μL, 0.790 mmol) were added and the reaction heated to 100° C. overnight. The reaction was cooled and diluted with water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified twice over silica gel (100% EtOAc) to afford (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)pyrrolidin-2-one (15.2 mg, 0.0321 mmol, 10.2% yield) as a red solid. Mass spectrum (apci) m/z=473.1 (M+H).

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified twice over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-48fa63662e844d52bf504336de7e3215
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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