Cyclopentamine

Originator

Clopane,Lilly,US,1951

Definition

ChEBI: Cyclopentamine is a secondary amino compound.

Manufacturing Process

A mixture of 126 g (1.5 mols) of cyclopentanone, 128 g (1.5 mols) cyanoacetic acid, 31 g (0.5 mol) of ammonium acetate and 200 cc of dry benzene is heated under a refluxing condenser and a water trap. The mixture is refluxed for about 12 hours after which time no more water collects in the trap, and the formation of cyclopentylideneacetonitrile is complete. The reaction mixture comprising a mixture of cyclopentylideneacetonitrile and cyclopentylideneacetic acid is washed with about one liter of 2% hydrochloric acid and the benzene layer is separated and the mixture is distilled to cause decarboxylation of the cyclopentylideneacetic acid present. The distillate comprising cyclopentylideneacetonitrile which boils at 172° to 175°C is purified by distillation.
A mixture of 53.5 g (0.5 mol) of cyclopentylideneacetonitrile dissolved in 50 cc of absolute ethanol and 0.5 g of a palladium-carbon catalyst is hydrogenated with hydrogen at a pressure of about 40 lb for about 3 hours. An additional amount of 0.8 g of palladium-carbon catalyst is then added and the hydrogenation continued for about 4 hours during which time the reduction is substantially completed and the cyclopentylideneacetonitrile is converted to cyclopentylacetonitrile. The reaction mixture is filtered to remove the catalyst and the alcohol is evaporated in vacuo.
The residue comprising chiefly cyclopentylacetonitrile is washed with dilute hydrochloric acid to remove any amine which may have been formed during the hydrogenation process, and the organic residue comprising cyclopentylacetonitrile is dissolved in ether, the ether solution dried over anhydrous magnesium sulfate and distilled. The cyclopentylacetonitrile boils at 185° to 187°C and has a refractive index of nD25 = 1.4456.
To an ethereal solution of methyl magnesium iodide prepared from 26.7 g (1.1 mols) of magnesium and 160 g (1.13 mols) of methyl iodide in 200 cc of dry ether, is added a solution of 79 g (0.72 mol) of cyclopentylacetonitrile in 100 cc of dry ether. The reaction mixture is refluxed for 4 hours. The reaction mixture is then decomposed with ice in the usual way, and the ether layer containing the cyclopentylacetone is separated, is dried over anhydrous magnesium sulfate and the ether removed by evaporation. The residue comprising cyclopentylacetone is purified by distillation in vacuo. The cyclopentylacetone boils at 82° to 84°C at about 32 mm pressure.
A mixture of 75 g (0.6 mol) of cyclopentylacetone, 75 g (2.4 mols) of methylamine, and 10 g of Raney nickel catalyst is placed in a high pressure bomb previously cooled to a temperature below -6°C, and hydrogen is admitted under an initial pressure of about 2,000 psi. The bomb is then heated to about 135° to 150°C for about 2 hours, during which time reductive amination takes place and 1-cyclopentyl-2-methylaminopropane is produced. During the period of heating the reaction mixture is agitated by rocking the bomb. The bomb is then cooled and opened thus permitting the escape of hydrogen and most of the excess methylamine. The reaction mixture is filtered to remove the nickel catalyst and the filtrate comprising 1-cyclopentyl- 2-methylaminopropane is purified by distillation under reduced pressure. 1- Cyclopentyl-2-methylaminopropane boils at 83° to 86°C at about 30 mm pressure.
1-Cyclopentyl-2-methylaminopropane thus produced is a colorless liquid of slightly ammoniacal odor. It has a refractive of nD25 = 1.4500. Analysis showed the presence of 9.79% N as compared with a calculated value of 9.99% N.
141 g (1 mol) of 1-cyclopentyl-2-methylaminopropane are dissolved in 500 cc of dry ether, and dry hydrogen chloride is passed into the solution until the weight of the mixture and container has increased by 36 g. During the addition of the hydrogen chloride, the hydrochloric acid addition salt of 1- cyclopentyl-2-methylaminopropane precipitates as a white powder. The salt is filtered off and washed with dry ether. 1-Cyclopentyl-2-methylaminopropane hydrochloride thus prepared melts at about 113° to 115°C. The yield is practically quantitative.

brand name

Clopane Hydrochloride (Lilly).

Therapeutic Function

Vasoconstrictor