Methylamine → (R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine

HRID 19002Notes

Reaction equation

HRID 19002 reaction equation
[CH3:1][C:2]1([CH3:24])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([N:13]3C(=O)C4C(=CC=CC=4)C3=O)=[N:9]2)[CH2:4][O:3]1.CN.CCCCCCC>C(OC)(C)(C)C.C(O)C>[CH3:1][C:2]1([CH3:24])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH2:13])=[N:9]2)[CH2:4][O:3]1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 8900HeptaneHCID 593449502-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-isoindole-1,3-dione

Product 1

HCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineYield 94.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

A suspension of 2-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-isoindole-1,3-dione (5.00 g, 15.3 mmol) in methyl t-butyl ether (50 mL) and ethanol (30 mL) was cooled with an ice water bath, and 33 wt. % methylamine in ethanol (20.0 mL, 161 mmol) was added. After 30 min, the mixture was warmed to room temperature and stirred for 2 h. Heptane (50 mL) was added and the mixture was cooled (−20° C.) for 30 min. The resulting solids were removed by filtration and rinsed with heptane. The filtrate was partially concentrated to a volume of ˜50 mL. The resulting solids were removed by filtration and rinsed with methyl t-butyl ether and heptane. After concentration of the filtrate to dryness, a yellow oil remained, which was then dissolved in methyl t-butyl ether (15 mL) and cooled (−20° C.) for 30 min. Addition of seed crystals and scratching with a spatula initiated crystallization of the product. Heptane (30 mL) was added and the suspension was cooled (−20° C.) for 30 min. Subsequent filtration, washing with heptane, and suction drying afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (2.85 g, 94.6%) as a white solid: LR-ES-MS m/z calculated for C9H15N3O2 [M]+ 197, observed [M+H]+ 198.

Workup

  1. temperaturewas cooled with an ice water bath
  2. temperaturethe mixture was cooled (−20° C.) for 30 min
  3. customThe resulting solids were removed by filtration
  4. washrinsed with heptane
  5. concentrationThe filtrate was partially concentrated to a volume of ˜50 mL
  6. customThe resulting solids were removed by filtration
  7. washrinsed with methyl t-butyl ether and heptane
  8. dissolutionwhich was then dissolved in methyl t-butyl ether (15 mL)
  9. temperaturecooled (−20° C.) for 30 min
  10. additionAddition of seed crystals
  11. customcrystallization of the product
  12. additionHeptane (30 mL) was added
  13. temperaturethe suspension was cooled (−20° C.) for 30 min
  14. filtrationSubsequent filtration
  15. washwashing with heptane, and suction
  16. customdrying

Sources & evidence

ORD record
ord-18562a0f55964658af000afb136b1e7f
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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