Diisopropylethylamine → tert-butyl (1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate

HRID 1915751Notes

Reaction equation

HRID 1915751 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].C[N:12]([CH2:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16].CCN(C(C)C)C(C)C>CCO>[CH3:7][N:6]1[C:2]([N:24]2[CH2:25][CH2:26][CH:21]([CH2:20][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18])[CH2:22][CH2:23]2)=[C:3]([N+:8]([O-:10])=[O:9])[CH:4]=[N:5]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 23004743tert-butyl N-methyl-N-(piperidin-4-ylmethyl)carbamate

Product 1

HCID 86679963tert-butyl (1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamateYield 81.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (0.2 g, 1.23 mmol), tert-butyl methyl(piperidin-4-ylmethyl)carbamate (0.29 g, 1.36 mmol) and DIPEA (1 mL, 5.7 mmol) in EtOH (3 mL) was heated at 130° C. in a microwave for 2 hr. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (40% EtOAc/isohexane) to give tert-butyl (1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate as a yellow oil (0.34 g, 80%). To a solution of this oil (0.15 mg, 0.44 mmol) in DMF (5 mL) cooled to 0° C. was added sodium hydride (27 mg, 0.66 mmol, 60% in mineral oil) and the mixture was stirred at 0° C. for 15 min. Iodomethane (0.03 mL, 0.53 mmol) was added and the mixture was stirred at 0° C. for 30 min. Additional sodium hydride (14 mg, 0.33 mmol) and iodomethane (0.02 mL, 0.78 mmol) were added, the reaction mixture was allowed to warm to 10° C. and stirred for 1 hr. Water (10 mL) was added and the mixture was extracted with EtOAc (60 mL). The organic layer was washed with water (7×10 mL), washed with brine (10 mL), separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification of the residue by silica gel column chromatography (30% EtOAc/isohexane) afforded tert-butyl methyl((1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-yl)methyl)carbamate as a yellow oil (148 mg, 95%). 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 3.74 (s, 3H), 3.38-3.26 (m, 2H), 3.25-3.15 (m, 2H), 3.12-2.95 (m, 2H), 2.89 (s, 3H), 1.90-1.71 (m, 3H), 1.60-1.32 (m, 2H), 1.47 (s, 9H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (40% EtOAc/isohexane)

Sources & evidence

ORD record
ord-7361cf380d904f84bca03e918b853ac1
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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