Acetonitrile → HCID 178432738, compound

HRID 2388007Notes

Reaction equation

HRID 2388007 reaction equation
[ClH:1].[CH3:2][N:3]([CH3:15])[CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[C:9]([NH2:14])[C:10]([CH3:13])=[N:11][CH:12]=1.C(#N)C.Cl.[Cl:20][C:21]([NH2:23])=[NH:22]>C(O)(=O)C>[ClH:20].[ClH:1].[ClH:20].[CH3:15][N:3]([CH3:2])[CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[C:9]([NH:14][C:21]([NH2:23])=[NH:22])[C:10]([CH3:13])=[N:11][CH:12]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 3084509Chloroformamidinium chlorideHCID 67336892HCID 67336892, compound

Product 1

HCID 178432738HCID 178432738, compoundYield 136.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
50 °C

Procedure

A 1 L, three-neck, round-bottom flask equipped with an overhead stirrer, a reflux condenser, an N2 inlet tube, and a temperature probe was charged with 5-(3-(dimethylamino)propyl)-2-methylpyridin-3-amine hydrochloride (25 g, 0.109 mol). Acetonitrile (275 mL, 11 vol) was added to it followed by acetic acid (25 mL, 1 vol). The initial suspension turned into a clear solution after the addition of acetic acid. Chloroformamidine hydrochloride (15.6 g, 0.136 mol, 1.25 equiv) was added to the solution resulting in a suspension. The reaction was heated at 40° C. for 30 min and at 50° C. for another 30 min. Then the temperature was raised to 60° C. and the reaction was continued at this temperature. After 1-2 h at 60° C., the reaction mixture became turbid and after 3-4 h, solid started separating out. The reaction was continued at 60° C. for 20 h and was judged complete by LC-MS analysis. The reaction was cooled to ambient temperature and the solid was collected by filtration (N2 flow was used during the filtration). The filter cake was washed with acetonitrile (50 mL, 2 vol). The solid was dried under high vacuum overnight to obtain N-{5-[3-(Dimethylamino)propyl]-2-methylpyridin-3-yl}guanidine trihydrochloride (32.1 g, 85% recovery) as a light brown solid. Elemental analysis Calcd: C, 41.81; H, 7.02; Cl, 30.85; N, 20.32. Found: C, 41.09; H, 6.72; Cl, 31.51; N, 20.47. 1H NMR (500 MHz, DA)) δ ppm: 8.57 (s, 1H), 8.45 (s, 1H), 3.22-3.19 (m, 2H), 2.90 (t, 2H, J=10 Hz), 2.86 (s, 6H), 2.69 (s, 3H), 2.15-2.07 (m, 2H); ESI-MS m/z 236 (M+H, 100%).

Workup

  1. customA 1 L, three-neck, round-bottom flask equipped with an overhead stirrer, a reflux condenser, an N2 inlet tube
  2. customresulting in a suspension
  3. temperatureThen the temperature was raised to 60° C.
  4. waitafter 3-4 h
  5. customsolid started separating out
  6. waitThe reaction was continued at 60° C. for 20 h
  7. temperatureThe reaction was cooled to ambient temperature
  8. filtrationthe solid was collected by filtration (N2 flow
  9. filtrationwas used during the filtration)
  10. washThe filter cake was washed with acetonitrile (50 mL, 2 vol)
  11. customThe solid was dried under high vacuum overnight

Sources & evidence

ORD record
ord-3bc86b0956c742428d4f6cab7bc3ce15
Source dataset
uspto-grants-2012_09
Patent number
US08268992B2

Reaction notes

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