Ammonia → 5-(2-Aminomethylprop-2-yl)-2-(4-pyridinyl)-benzimidazole

HRID 1639133Notes

Reaction equation

HRID 1639133 reaction equation
C([NH:4][CH2:5][C:6]([C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([NH2:16])[CH:10]=1)([CH3:8])[CH3:7])(=O)C.C(N(CC)CC)C.Cl.[C:25](Cl)(=O)[C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.N>O.ClCCl>[NH2:4][CH2:5][C:6]([C:9]1[CH:14]=[CH:13][C:12]2[N:15]=[C:25]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)[NH:16][C:11]=2[CH:10]=1)([CH3:7])[CH3:8]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 12262826Isonicotinoyl chloride hydrochlorideHCID 141530264-(2-Acetamidomethylprop-2-yl)-1,2-diaminobenzene

Product 1

HCID 141530275-(2-Aminomethylprop-2-yl)-2-(4-pyridinyl)-benzimidazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 22.1 g. 4-(2-acetamidomethylprop-2-yl)-1,2-diaminobenzene and 42 ml. triethylamine in 500 ml. dichloromethane are added, while cooling with ice water, 27 g. isonicotinic acid chloride hydrochloride. Stirring is continued at ambient temperature until the reaction of the diamine is complete (thin layer chromatography, silica gel, dichloromethane:methanolic ammonia=10:1 v/v). It is shaken with water and the organic phase is separated off and evaporated to dryness in a vacuum. The residue (24.3 g.) is taken up in 200 ml. ethanol, mixed with 60 ml. concentrated hydrochloric acid and boiled under reflux for 3 days. It is evaporated to dryness in a vacuum, the residue is digested with aqueous ammonia solution at pH=6, 50 ml. dichloromethane are added thereto, filtered off with suction and then washed with iced water and dichloromethane to give 14.1 g. of colourless crystals which are purified by column chromatography (column: diameter 6 cm., length 40 cm., filled with 1 liter silica gel, elution agent dichloromethane:methanolic ammonia 15:1 v/v). After combining the appropriate fractions, removing the elution agent in a vacuum and triturating with ethyl acetate, there are obtained 9.2 g. of the title compound as colourless crystals; m.p. 199°-202° C. 2.7 g. thereof are recrystallised from dioxan to give 2.3 g. of colourless crystals; m.p. 203°- 204° C.

Workup

  1. customthe organic phase is separated off
  2. customevaporated to dryness in a vacuum
  3. additionethanol, mixed with 60 ml
  4. temperatureunder reflux for 3 days
  5. customIt is evaporated to dryness in a vacuum
  6. additiondichloromethane are added
  7. filtrationfiltered off with suction
  8. washwashed with iced water and dichloromethane
  9. customto give 14.1 g
  10. customof colourless crystals which are purified by column chromatography (column: diameter 6 cm., length 40 cm., filled with 1 liter silica gel, elution agent dichloromethane:methanolic ammonia 15:1 v/v)
  11. customremoving the elution agent in a vacuum
  12. customtriturating with ethyl acetate, there
  13. customare obtained 9.2 g

Sources & evidence

ORD record
ord-b75f0f0f89d54142be4fe78bf8d08877
Source dataset
uspto-grants-1989_11
Patent number
US04882342

Reaction notes

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