Hydrochloric Acid → ({1-[(2-chlorophenyl)methyl]-3,5-dimethyl-1H-pyrazol-4-yl}methyl)(methyl)amine

HRID 238122Notes

Reaction equation

HRID 238122 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][N:5]1[C:9]([CH3:10])=[CH:8][C:7]([CH3:11])=[N:6]1.C=O.[CH3:18][NH2:19].Cl.[CH3:21]O>>[Cl:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH2:18][NH:19][CH3:21])[C:7]([CH3:11])=[N:6]1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 887MethanolHCID 6329MethylamineHCID 6618091-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole

Product 1

HCID 2466725({1-[(2-chlorophenyl)methyl]-3,5-dimethyl-1H-pyrazol-4-yl}methyl)(methyl)amineYield 62%

Conditions

Temperature
60 °C

Procedure

A solution of 1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazole (1.00 g, 4.53 mmol), paraformaldehyde (0.82 g, 27.20 mmol) and methylamine.HCl (0.92 g, 13.59 mmol) dissolved in methanol (9.06 ml) was stirred at 60° C. for 24 hrs. The mixture was cooled to room temperature and quenched with aqueous NaHCO3 (15 mL). The aqueous layer was extracted 3 times with ether (15 mL) and the combined organic layers washed with brine (30 mL). The organic layer was dried with MgSO4 and concentrated under reduced pressure. The resulting yellow oil was purified using flash column chromatography with 1:4:0.01 ethyl acetate:hexanes:triethylamine as eluting solvent yielding 0.73 g (62%) of 1-(1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine as a clear oil. 1H NMR (300 MHz, CDCl3) δ 7.40-7.31 (m, 1H), 7.23-7.08 (m, 2H), 6.54-6.43 (m, 1H), 5.32 (s, 2H), 3.31 (s, 2H), 2.91 (s, 1H), 2.25 (s, 3H), 2.16 (s, 3H), 2.12 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 148.12, 138.48, 135.57, 131.94, 129.42, 128.72, 127.61, 127.41, 114.38, 50.24, 49.08, 40.68, 12.36, 9.75. HRMS (m/z): [MH]+ calc for C14H18ClN3, 264.13. found 264.1253.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customquenched with aqueous NaHCO3 (15 mL)
  3. extractionThe aqueous layer was extracted 3 times with ether (15 mL)
  4. washthe combined organic layers washed with brine (30 mL)
  5. dry with materialThe organic layer was dried with MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting yellow oil was purified
  8. washhexanes:triethylamine as eluting solvent

Sources & evidence

ORD record
ord-f9d761060b3d416ebab19dc2b5f2d1ff
Source dataset
uspto-grants-2014_02
Patent number
US08642614B2

Reaction notes

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