Triethylamine → 5-(1-methyl-4-nitro-1H-pyrazol-5-yl)-5,8-diazaspiro[2.6]nonane

HRID 1915803Notes

Reaction equation

HRID 1915803 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(CC)CC)C.[F-].[K+].Br.Br.[CH2:22]1[C:24]2([CH2:30][NH:29][CH2:28][CH2:27][NH:26][CH2:25]2)[CH2:23]1>CS(C)=O.CCOC(C)=O>[CH3:7][N:6]1[C:2]([N:26]2[CH2:27][CH2:28][NH:29][CH2:30][C:24]3([CH2:22][CH2:23]3)[CH2:25]2)=[C:3]([N+:8]([O-:10])=[O:9])[CH:4]=[N:5]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 522689Potassium FluorideHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 866800115,8-Diazaspiro[2.6]nonane dihydrobromide

Product 1

HCID 866800105-(1-methyl-4-nitro-1H-pyrazol-5-yl)-5,8-diazaspiro[2.6]nonaneYield 30.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-chloro-1-methyl-4-nitro-1H-pyrazole (323 mg, 2.0 mmol), triethylamine (0.7 mL, 5.0 mmol) and potassium fluoride (581 mg, 10.0 mmol) in dry DMSO (20 mL) was added 5,8-diazaspiro[2.6]nonane dihydrobromide (686 mg, 2.4 mmol) and the mixture was heated in the microwave at 65° C. for 4 hr. The mixture was diluted with EtOAc (30 mL) and washed with saturated aqueous NaHCO3 (3×20 mL). The aqueous layer was further extracted with DCM (3×20 mL) and the combined organic layers passed through a phase separation cartridge and concentrated under reduced pressure. The residue was loaded onto an SCX-2 column which was washed with MeOH and eluted with 3% 7M ammonia in MeOH/DCM and concentrated under reduced pressure to give 5-(1-methyl-4-nitro-1H-pyrazol-5-yl)-5,8-diazaspiro[2.6]nonane as a yellow gum (153 mg). To a solution of this intermediate in DCM (10 mL) was added di-tert-butyl dicarbonate (157 mg, 0.72 mmol) and DMAP (4 mg, 0.03 mmol) and the mixture stirred at room temperature for 2 hr. The mixture was washed with water (3×10 mL) and the organic layer separated, passed through a phase separation cartridge and concentrated under reduced pressure to give tert-butyl 8-(1-methyl-4-nitro-1H-pyrazol-5-yl)-5,8-diazaspiro[2.6]nonane-5-carboxylate as a yellow gum (200 mg, 28% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.02 and 8.00 (2s, 1H), 3.85-3.77 (m, 3H), 3.75-3.67 (m, 2H), 3.47-3.27 (m, 4H), 3.29-2.97 (m, 2H), 1.49 (s, 9H), 0.73-0.55 (m, 2H), 0.47-0.38 (m, 2H).

Workup

  1. washwashed with saturated aqueous NaHCO3 (3×20 mL)
  2. extractionThe aqueous layer was further extracted with DCM (3×20 mL)
  3. customthe combined organic layers passed through a phase separation cartridge
  4. concentrationconcentrated under reduced pressure
  5. washwas washed with MeOH
  6. washeluted with 3% 7M ammonia in MeOH/DCM
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-822c2f1ede96440b8dba515a861c4245
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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