Sodium cyanoborohydride → N-Methyl-N-((1-methyl-3-nitro-1H-pyrazol-5-yl)methyl)oxetan-3-amine

HRID 593100Notes

Reaction equation

HRID 593100 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[N:8]([CH3:9])[N:7]=[C:6]([N+:10]([O-:12])=[O:11])[CH:5]=1.[O:13]1[CH2:16][C:15](=O)[CH2:14]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[CH3:1][N:2]([CH2:3][C:4]1[N:8]([CH3:9])[N:7]=[C:6]([N+:10]([O-:12])=[O:11])[CH:5]=1)[CH:15]1[CH2:16][O:13][CH2:14]1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 58044304Methyl[(1-methyl-3-nitro-1H-pyrazol-5-YL)methyl]amine

Product 1

HCID 58043818N-Methyl-N-((1-methyl-3-nitro-1H-pyrazol-5-yl)methyl)oxetan-3-amineYield 80%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 302a (170 mg, 1 mmol) in methanol (4 mL), ZnCl2 (1 mmol/L in diethyl ether) (2 mL, 2 mmol) and oxetan-3-one (150 mg, 2 mmol) were added at room temperature under nitrogen protection, followed by the addition of NaBH3CN (130 mg, 2 mmol). The reaction mixture was warmed to 50° C. and stirred for 3 h. The mixture was then cooled to room temperature and the solvent was removed. The residue was purified on flush column eluting with 50:1 methylene chloride/methanol to afford 302b as a yellow solid (180 mg, 80%, two steps). LCMS: (M+H)+ 227. 1H NMR (500 MHz, DMSO) δ 6.99 (s, 1H), 4.52 (t, J=6.5, 2H), 4.42 (t, J=6, 2H), 3.98 (s, 3H), 3.63 (m, 1H), 3.50 (s, 2H), 2.03 (s, 3H).

Workup

  1. additionwere added at room temperature under nitrogen protection
  2. temperatureThe mixture was then cooled to room temperature
  3. customthe solvent was removed
  4. customThe residue was purified
  5. customon flush column
  6. washeluting with 50:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-046553a9b4154bc986fdde8c9962be1e
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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