Diisopropylethylamine → 3-chloro-5-((2R,3R)-2-methyl-3-(3-methyl-2-oxoimidazolidin-1-yl)piperidin-1-yl)pyrazine-2-carbonitrile

HRID 1050576Notes

Reaction equation

HRID 1050576 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][N:4]([C@@H:7]2[CH2:12][CH2:11][CH2:10][NH:9][C@@H:8]2[CH3:13])[C:3]1=[O:14].[Cl:15][C:16]1[C:17]([C:23]#[N:24])=[N:18][CH:19]=[C:20](Cl)[N:21]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:15][C:16]1[C:17]([C:23]#[N:24])=[N:18][CH:19]=[C:20]([N:9]2[CH2:10][CH2:11][CH2:12][C@@H:7]([N:4]3[CH2:5][CH2:6][N:2]([CH3:1])[C:3]3=[O:14])[C@H:8]2[CH3:13])[N:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 529877443,5-Dichloropyrazine-2-carbonitrileHCID 1181153891-methyl-3-((2R,3R)-2-methylpiperidin-3-yl)imidazolidin-2-one

Product 1

HCID 1181334303-chloro-5-((2R,3R)-2-methyl-3-(3-methyl-2-oxoimidazolidin-1-yl)piperidin-1-yl)pyrazine-2-carbonitrileYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 356 from above was dissolved in 10 mL DMF. To it were added 3,5-dichloropyrazine-2-carbonitrile (250 mg, 1.42 mmol) and DIEA (500 μL, 2.84 mmol). The mixture was stirred at RT for 2 hours, diluted with 150 mL EtOAc, washed with water ×3, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 3% MeOH in DCM to isolate 3-chloro-5-((2R,3R)-2-methyl-3-(3-methyl-2-oxoimidazolidin-1-yl)piperidin-1-yl)pyrazine-2-carbonitrile (357, 200 mg, 42% yield).

Workup

  1. washwashed with water ×3
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-79a4064ad6e84905b945e86785d1f6b3
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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