Hydrochloric Acid → (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile

HRID 1050533Notes

Reaction equation

HRID 1050533 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14]C(=O)OC(C)(C)C)[CH2:9]2)[CH:5]=[N:4][C:3]=1[C:22]#[N:23].Cl>O1CCOCC1>[NH2:14][C@@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]2[N:7]=[C:2]([Cl:1])[C:3]([C:22]#[N:23])=[N:4][CH:5]=2)[CH2:9]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118114972(R)-tert-butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate

Product 1

HCID 118114942(R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(R)-tert-Butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (87, 2.00 g, 5.93 mmol) was treated with 25 mL commercial 4N HCl in dioxane at RT for 2 hours. It was concentrated in vacuo to afford crude (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile (221) hydrochloride as white solid. It was dissolved in 10 mL DMF and 50 mL dioxane. To it were added DIEA (8.25 mL, 47.4 mmol) and then dropwise dimethylcarbamoyl chloride (1.64 mL, 17.8 mmol). The mixture was stirred at RT for 3 hours. It was concentrated in vacuo, diluted with 200 mL EtOAc, washed with water ×2, dried, concentrated in vacuo, subjected to silica flash column using 0 to 4% MeOH in DCM to isolate (R)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1,1-dimethylurea (222) (1.47 g, 80%) as a white solid.

Workup

  1. concentrationIt was concentrated in vacuo

Sources & evidence

ORD record
ord-a6e2e3d88b3e4579bc1a9877e92dca8c
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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