5-chloro-1-methyl-4-nitro-1H-pyrazole → HCID 58465025, compound

HRID 2089357Notes

Reaction equation

HRID 2089357 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH3:11][N:12]1[CH2:17][CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH2:14][CH2:13]1.C([O-])([O-])=O.[Na+].[Na+].CC([O-])=O.[K+]>CC#N.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:11][N:12]1[CH2:13][CH:14]=[C:15]([C:2]2[N:6]([CH3:7])[N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:16][CH2:17]1

Participants

6

Reactant 3

HCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 86658407HCID 86658407, compound

Product 1

HCID 58465025HCID 58465025, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

5-Chloro-1-methyl-4-nitro-1H-pyrazole (0.2 g, 1.24 mmol), 1-methyl-1,2,3,6 tetrahydropyridine-4-boronic acid pinacol ester (0.553 g, 2.48 mmol) and Pd(dppf)2Cl2 (0.02 g, 0.025 mmol) were suspended in degassed MeCN (5 mL). Aqueous Na2CO3/KOAc solution (1:1, 1.1 M, 1.5 mL) was added and the mixture was heated at 130° C. in a microwave for 40 min. A further portion of Pd(dppf)2Cl2 (0.1 g, 0.12 mmol) was added and the mixture was heated at 130° C. for a further 90 min. The solvents were removed under reduced pressure and the crude residue dissolved in EtOAc and water. The mixture was extracted with EtOAc and the combined organic layers passed through a phase separator cartridge. The solvent was removed under reduced pressure and the crude product was purified via silica gel column chromatography (0-10% MeOH/DCM) to give 1-methyl-4-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,2,3,6-tetrahydropyridine as a brown oil (44 mg, 16%). 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 5.89-5.86 (m, 1H), 3.82 (s, 3H), 3.19 (q, J=3.0 Hz, 2H), 2.74 (q, J=5.5 Hz, 2H), 2.47-2.39 (m, 5H)

Workup

  1. temperaturethe mixture was heated at 130° C. for a further 90 min
  2. customThe solvents were removed under reduced pressure
  3. dissolutionthe crude residue dissolved in EtOAc
  4. extractionThe mixture was extracted with EtOAc
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was purified via silica gel column chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-ddd6562a6ecd41d1a0d9b3231c015dd6
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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