Patented Sept. 27, 1932
`
`1,879,003
`
`UNITED STATES
`
`PATENT OFFICE
`
`GORDON A. ALI.-E8, OP IIIONTEEIEI PARK, CALEORHIA
`
`BAI-1'8 OI‘ 1-PHIEiN'YI.-9-A.'Il.'IK-DPBOPAJTE
`
`Ho Drawing.
`
`Application filed fieptember 8, 1380.
`
`I-arial no. 179.1127.
`
`This invention relates to a new composi-
`tion of matter useful for therapeutic pur-
`poses.
`The composition of matter of my present
`5 invention consists of a salt of 1-phen§l-2-
`aminopropane, CaHa - CH2 - CH ( L Ha) H-.-,
`with an acid. Various acids may be used,
`the most useful being hydrochloric or sul-
`phuric. The salts of this 1-phenyl-2-aminm
`lo propane are physiolo ically active and pro-
`duce effects in animails and man similar to
`the effect. of the salts of ephedrine and may
`be readily purified by crystallization and
`serve as effective agents for the administra-
`15 tion of this amine. The method of making
`such salts preferably comprises synthesizing
`the 1-plienyl—2—a1ni11o Jropane, and then con-
`vcrting the 1-phony -2-aminopropane to a
`salt thereof, and the last mentioned conver-
`20 sion may be used for the purification or isola-
`tion of
`the 1-phenyl-2-aminopropane, and
`the formation of a salt thereof, regardless of
`wliether the 1-phenyl-2-aminopropane is pre-
`pared by the method of synthesis herein de-
`en scribed or by any other method.
`The preferred method of synthesizing the
`1~phcnyl-2-aminopropane,
`
`C.,H,-CH,-CH (CH, ) NH2,
`
`so is by the reduction of the henyl-nitropropy-
`Iene, CGH,-CH=C CH,)gI0, This reduc-
`tion may he carri
`out by sodium-mercury
`amalgam in an ethanol-acetic acid solution or
`hy electrolytic reduction at a metal cathode
`in a suitable solution. This cathodic reduc-
`tion can be carried out with good yield in the
`following manner:
`One mol of
`the phenyl-nitropropylene,
`
`35
`
`C,,H,.CH=C(CH,) N02,
`
`is dissolved with a solvent prepared by mix-
`ing one liter of ethanol with one-half liter of
`acetic acid and onc—half liter of twelve nor-
`mal sulphuric acid. The resultant solution
`-'5 is placed in the cathode compartment of a
`divided electrolytic cell containing a metal-
`lic cathode of mercury, copper, or other metal
`of similar nature. Current is passed, using a
`current density of about two-tenths am ere
`5° per square centimeter of cathode sur ace.
`
`The temperature is kept. about 40° C. during
`the electrol sis which is continued until at.
`least Eight
`aradays of electricity have been
`passe .
`.
`When the reduction is completed,
`the
`1-phen 1-2-aminopropane may be separated
`from t a solution. A convenient way of do-
`ing this is by removing the ethanol and eth l
`acetate present by evaporation and then ma -
`inig the residual solution stron ly alkaline by
`a dition of caustic alkali. T e basic layer
`thus formed is separated from the a ueous
`solution and contains the desired 1-p enyl-
`2-aminopropane.
`Such a product, however, as thus obtained,
`is in a. crude or somewhat impure state, be-
`ing contaminated by the presence of small
`amounts of other materials, such as side
`products of the reduction reaction. This con-
`dition is true, moreover, regardless of the
`particular method of synthesis employed,
`and it is therefore necessary in an
`case,
`when it is desired to obtain the product in
`suitable form for therapeutic administration,
`to further isolate or purify the compound,
`and it will be understood that the -hereinafter
`described method of isolation is of general
`application for this purpose, as applied to
`any 1-phenyl-2-aminopropane product, re-
`gardless of the method by which the product
`ma have been synthesized.
`gccording to my invention the isolation or
`purification of the 1-phcnyl-2-arninopropane
`is effected by exactly neutralizing the impure
`product with an acid, such as hydrochloric
`or sulphuric acid, in aqueous solution fol-
`lowed by crystallization from water, alcohol,
`acetone or suitable solution. The 1-phenyl-
`2-amincpropane is thus converted into a salt
`of the acid used. For example, if hydro-
`chloric acid is used,
`it. is converted into its
`hydrochloride,
`
`0.1-I.-CH,-CH ( CH.) NI-I,,.HCl,
`
`SIT
`
`70
`
`75
`
`B0
`
`which readily crystallizes from alcohol or
`acetone without solvent of crystallization, or
`if sulphuric acid is used it is converted into
`its neutral sulphate,
`
`[CJL-CH:-CH (CH.)NHa] 2-HxS0.,
`
`100
`
`Amerigen Ex. 1062, p. 1
`Amerigen Ex. 1062, p. 1
`
`

`
`2
`
`1.37-9,ooa
`
`_
`
`atallizea from water or al-
`which readily c
`cohol without so vent of crystallization.
`The h droehloride and neutral sulphate of
`1-phen -2-aininopro ane give analyses cor-
`, respon iiig to the ollowing formulae and
`have melting
`iiits as listed: 1-phenyl-2-
`aminopropane ydrochloride
`
`C.M.-CH2-CH(CH,) NH,.HCl M.144-5° C.
`
`10 1-phony]-2-aminopropane sulphate
`
`[C.H.-CH,~CH (CH.) NH,],.II,S0.
`M. above 285“ C.
`
`The recrystallized and purified material
`15 may be dissolved in water, alcohol or other
`suitable solvent for the purpose of thera-
`peutic administration.
`It will be seen, therefore, that the conver-
`sion of 1-phenyl-2-aiiiinopropane to a salt
`29 thereof not only offers a simple and conven-
`ient method of purification or isolation there-
`of from the impurities with which the prod-
`uct obtained by synthesis is ordinarily con-
`taminated, but also provides a highly advan-
`25 ta eous means of therapeutic use thereof.
`he above described method of synthesis
`of Lphenyl-2-aminopropane is believed to be
`a new and useful method of preparation of
`such an amine, independent of the subsequent
`30 conversion thereof into a salt, and said meth-
`od is claimed in a separate application Ser.
`No. 479,428, filed by me of even date here-
`with.
`I claim:
`
`35
`
`1. As a new composition of matter, a salt
`of 1-phenyl-2-amiiiopropane.
`2. As a new composition of matter, the hy-
`drochloride of 1-phenyl-2-anriinopropane.
`In testimony whereof I have hereunto sub-
`4o scribed my name this 29th day of August,
`1930.
`
`GORDON A. ALLES.
`
`DISCLAIMER
`
`l,879,003.—-Gordon. A. Alias, Monterey Park, Calif. Saurs or l-Pi~mNi'L-2-AMiNo-
`PROPANE. Patent dated September 27, 1932. Disclaimer filed August
`29, 1934, by the patentee.
`_ Hereby enters this dislaimer to that part of the claims in said specification of
`said atent which is as follows, to wit:
`e disclaims so much of claim 1 of said patent as is in excess of the following:
`_ “As a ph_vsiol‘ogically active therapeutic agent. capable of producing effects in
`animals and man similar to the effect of salts of ephedrine, a salt of 1-pheiiyl-2-amino-
`propane.”
`He disclaims so inuch of claim 2 of said patent as is in excess of the following:
`"As a (physiologically active t-lierapeutic agent ca able of producin effects in
`_
`animals an _nian similar to the effect of salts of eph
`no, the hydrocli oride of 1-
`phenyl-2-aniinopi-opane.”
`[0f}icml Gazette September 18, 1934.]
`
`Amerigen Ex. 1062, p. 2
`Amerigen Ex. 1062, p. 2
`
`

`
`2
`
`1.37-9,ooa
`
`_
`
`atallizea from water or al-
`which readily c
`cohol without so vent of crystallization.
`The h droehloride and neutral sulphate of
`1-phen -2-aininopro ane give analyses cor-
`, respon iiig to the ollowing formulae and
`have melting
`iiits as listed: 1-phenyl-2-
`aminopropane ydrochloride
`
`C.M.-CH2-CH(CH,) NH,.HCl M.144-5° C.
`
`10 1-phony]-2-aminopropane sulphate
`
`[C.H.-CH,~CH (CH.) NH,],.II,S0.
`M. above 285“ C.
`
`The recrystallized and purified material
`15 may be dissolved in water, alcohol or other
`suitable solvent for the purpose of thera-
`peutic administration.
`It will be seen, therefore, that the conver-
`sion of 1-phenyl-2-aiiiinopropane to a salt
`29 thereof not only offers a simple and conven-
`ient method of purification or isolation there-
`of from the impurities with which the prod-
`uct obtained by synthesis is ordinarily con-
`taminated, but also provides a highly advan-
`25 ta eous means of therapeutic use thereof.
`he above described method of synthesis
`of Lphenyl-2-aminopropane is believed to be
`a new and useful method of preparation of
`such an amine, independent of the subsequent
`30 conversion thereof into a salt, and said meth-
`od is claimed in a separate application Ser.
`No. 479,428, filed by me of even date here-
`with.
`I claim:
`
`35
`
`1. As a new composition of matter, a salt
`of 1-phenyl-2-amiiiopropane.
`2. As a new composition of matter, the hy-
`drochloride of 1-phenyl-2-anriinopropane.
`In testimony whereof I have hereunto sub-
`4o scribed my name this 29th day of August,
`1930.
`
`GORDON A. ALLES.
`
`DISCLAIMER
`
`l,879,003.—-Gordon. A. Alias, Monterey Park, Calif. Saurs or l-Pi~mNi'L-2-AMiNo-
`PROPANE. Patent dated September 27, 1932. Disclaimer filed August
`29, 1934, by the patentee.
`_ Hereby enters this dislaimer to that part of the claims in said specification of
`said atent which is as follows, to wit:
`e disclaims so much of claim 1 of said patent as is in excess of the following:
`_ “As a ph_vsiol‘ogically active therapeutic agent. capable of producing effects in
`animals and man similar to the effect of salts of ephedrine, a salt of 1-pheiiyl-2-amino-
`propane.”
`He disclaims so inuch of claim 2 of said patent as is in excess of the following:
`"As a (physiologically active t-lierapeutic agent ca able of producin effects in
`_
`animals an _nian similar to the effect of salts of eph
`no, the hydrocli oride of 1-
`phenyl-2-aniinopi-opane.”
`[0f}icml Gazette September 18, 1934.]
`
`Amerigen Ex. 1062, p. 3
`Amerigen Ex. 1062, p. 3