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

HRID 1050588Notes

Reaction equation

HRID 1050588 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][N:4]([C@@H:8]2[CH2:13][CH2:12][CH2:11][NH:10][C@@H:9]2[CH3:14])[C:3]1=[O:15].[Cl:16][C:17]1[C:18]([C:24]#[N:25])=[N:19][CH:20]=[C:21](Cl)[N:22]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:16][C:17]1[C:18]([C:24]#[N:25])=[N:19][CH:20]=[C:21]([N:10]2[CH2:11][CH2:12][CH2:13][C@@H:8]([N:4]3[CH2:5][CH2:6][CH2:7][N:2]([CH3:1])[C:3]3=[O:15])[C@H:9]2[CH3:14])[N:22]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 529877443,5-Dichloropyrazine-2-carbonitrileHCID 1181334331-methyl-3-((2R,3R)-2-methylpiperidin-3-yl)tetrahydropyrimidin-2(1H)-one

Product 1

HCID 1181150663-chloro-5-((2R,3R)-2-methyl-3-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)piperidin-1-yl)pyrazine-2-carbonitrileYield 31.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Methyl-3-((2R,3R)-2-methylpiperidin-3-yl)tetrahydropyrimidin-2(1H)-one (404, 120 mg, 0.55 mmol) was dissolved in 10 mL DMF. To it were added 3,5-dichloropyrazine-2-carbonitrile (175 mg, 1.0 mmol) and DIEA (350 μL, 2.0 mmol). The mixture was stirred at RT for 30 mM, diluted with 150 mL EtOAc, washed with water ×3, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 3.5% MeOH in DCM to isolate 3-chloro-5-((2R,3R)-2-methyl-3-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)piperidin-1-yl)pyrazine-2-carbonitrile (405, 60 mg, 31% yield).

Workup

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

Sources & evidence

ORD record
ord-1d1bad20813d41edb8f5bf3c1d219c2e
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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