Diisopropylethylamine → tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

HRID 1050560Notes

Reaction equation

HRID 1050560 reaction equation
[CH3:1][C@@H:2]1[C@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:6][CH2:5][CH2:4][NH:3]1.CCN(C(C)C)C(C)C.[Cl:25][C:26]1[C:27]([C:33]#[N:34])=[N:28][CH:29]=[C:30](Cl)[N:31]=1>C1COCC1>[Cl:25][C:26]1[N:31]=[C:30]([N:3]2[CH2:4][CH2:5][CH2:6][C@@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C@H:2]2[CH3:1])[CH:29]=[N:28][C:27]=1[C:33]#[N:34]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 40152174tert-butyl N-[(2R,3R)-2-methylpiperidin-3-yl]carbamateHCID 529877443,5-Dichloropyrazine-2-carbonitrile2×

Product 1

HCID 118136131tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl (2R,3R)-2-methylpiperidin-3-ylcarbamate (310) (1.1 g, 5.1 mmol) was dissolved in THF (20 mL). To the stirred solution was added DIEA (1.34 mL, 7.7 mmol), followed by 3,5-dichloropyrazine-2-carbonitrile (1.07 g, 6.2 mmol). The reaction was stirred at room temperature for 1 hour. An additional amount of 3,5-dichloropyrazine-2-carbonitrile (200 mg, 1.2 mmol) was added, and the reaction was stirred for another hour. The solvent was removed under reduced pressure, and the residue was suspended in EtOAc. The organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine, dried, and concentrated in vacuo. The residue was then purified by silica flash column chromatography (EtOAc/hexanes) to give tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (311), (1.54 g, 4.38 mmol, 86% yield).

Workup

  1. stirringthe reaction was stirred for another hour
  2. customThe solvent was removed under reduced pressure
  3. washThe organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was then purified by silica flash column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-4fdd0dec6e7b4ccb9abd22b42f95966f
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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