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

HRID 521248Notes

Reaction equation

HRID 521248 reaction equation
[C:1]([CH:3]=[C:4]1[CH2:9][CH2:8][N:7]([C:10]([O-:12])=[O:11])[CH2:6][CH:5]1[F:13])#[N:2].[NH2:14][C:15]1[C:19]([C:20]([NH2:22])=[O:21])=[CH:18][NH:17][N:16]=1.[CH2:23]1[CH2:33][CH2:32]N2C(=NCCC2)CC1.[CH3:34]C#N>CCOC(C)=O>[NH2:14][C:15]1[C:19]([C:20](=[O:21])[NH2:22])=[CH:18][N:17]([C:4]2([CH2:3][C:1]#[N:2])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:33]([CH3:23])([CH3:34])[CH3:32])=[O:11])[CH2:6][CH:5]2[F:13])[N:16]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 867294264-(Cyanomethylidene)-3-fluoropiperidine-1-carboxylateHCID 178513763HCID 178513763, compound

Product 1

HCID 86729425tert-Butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)-3-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (4E and 4Z)-4-(cyanomethylidene)-3-fluoropiperidine-1-carboxylate (800 mg, 3.33 mmol) in MeCN (10 mL) were added 3-amino-1H-pyrazole-4-carboxamide (350 mg, 2.78 mmol) and DBU (0.837 mL, 5.55 mmol). The solution was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with EtOAc and washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The oily residue was purified by MPLC on silica gel (0-100% EtOAc/hexanes) to afford the title compound as a mixture of diastereomers. LRMS (ESI) calc'd for C16H23FN6O3 [M+H]+: 367. Found: 367.

Workup

  1. washwashed with brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe oily residue was purified by MPLC on silica gel (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2d6d9d7281a248b3bb06502f80e71d1b
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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