Acetonitrile → tert-Butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate

HRID 521206Notes

Reaction equation

[NH2:1][C:2]1[C:6]([C:7]([NH2:9])=[O:8])=[CH:5][NH:4][N:3]=1.[C:10]([CH:12]=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)#[N:11].C(#N)C.C1CCN2C(=NCCC2)CC1>O>[NH2:1][C:2]1[C:6]([C:7](=[O:8])[NH2:9])=[CH:5][N:4]([C:13]2([CH2:12][C:10]#[N:11])[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:17][CH2:18]2)[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-Amino-1H-pyrazole-4-carboxamide (0.80 g, 6.3 mmol) and tert-butyl 4-(cyanomethylene)piperidine-1-carboxylate (2.1 g, 9.5 mmol) were combined with acetonitrile (31 mL) in a pressure vessel. DBU (1.05 mL, 6.98 mmol) was then added at ambient temperature. The reaction vessel was sealed and the mixture was heated to 80° C. for 16 hours. The reaction mixture was then allowed to cool to ambient temperature before water (150 mL) was added. The aqueous mixture was extracted with EtOAc (2×). The organic layers were then combined and washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was adsorbed on silica gel in vacuo and purified by MPLC on silica gel (using a gradient elution of 75-100% EtOAc/hexanes) to afford the title compound, Intermediate #35-1.

Workup

customThe reaction vessel was sealed
additionwas added
extractionThe aqueous mixture was extracted with EtOAc (2×)
washwashed with brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by MPLC on silica gel (
washa gradient elution of 75-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-28ef118ca9f44639af29833816239e59
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328099B2

Reaction notes

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