Piperidinocarbonitrile → N-[5-(5-amino-[1,2,4]oxadiazol-3-yl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 719877Notes

Reaction equation

HRID 719877 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([C:22](=[NH:25])[NH:23][OH:24])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[C:32](N1CCCCC1)#[N:33]>>[NH2:33][C:32]1[O:24][N:23]=[C:22]([C:19]2[N:20]=[CH:21][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]3[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=3)[CH2:26][CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)=[N:17][CH:18]=2)[N:25]=1

Participants

3

Reactant 2

HCID 73736PiperidinocarbonitrileHCID 178504753HCID 178504753, compound

Product 1

HCID 10005817N-[5-(5-amino-[1,2,4]oxadiazol-3-yl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 37%

Conditions

Temperature
130 °C

Procedure

A mixture of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(N-hydroxycarbamimidoyl)-pyrazin-2-yl]-propionamide (prepared as in Example 1, 7.00 g, 15.02 mmol) in N-cyanopiperidine (25 mL) was heated at 130° C. in a sealed tube for 1.5 h. The mixture was allowed to cool to 25° C. and then concentrated under a stream of anhydrous nitrogen overnight. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/2 ethyl acetate/hexanes) afforded the N-[5-(5-amino-[1,2,4]oxadiazol-3-yl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (2.74 g, 37%) as an off-white solid: mp 262–264° C.; (ES)+-HRMS m/e calcd for C21H23ClN6O4S2 (M+Na)+ 513.1082, found 513.1088.

Workup

  1. temperatureto cool to 25° C.
  2. concentrationconcentrated under a stream of anhydrous nitrogen overnight

Sources & evidence

ORD record
ord-dd8fc1d5309a46b597047bf2c4d77c52
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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