CN108341793A - 4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide novel crystal forms and preparation method - Google Patents
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide novel crystal forms and preparation method Download PDFInfo
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- CN108341793A CN108341793A CN201710055758.9A CN201710055758A CN108341793A CN 108341793 A CN108341793 A CN 108341793A CN 201710055758 A CN201710055758 A CN 201710055758A CN 108341793 A CN108341793 A CN 108341793A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention discloses 4 [2（2 methyl, 4 three deuterium methylbenzene sulfydryl）Phenyl] piperazine hydrobromide novel crystal forms and preparation method thereof.The 2 θ values of X ray powder diffractions characteristic peak of the alpha-crystal form are 5.81,7.04,9.23,14.10,16.30,17.49,18.21,18.58,20.51,21.20,22.98,28.12,31.49；The 2 θ values of X ray powder diffractions characteristic peak of the beta crystal are 6.86,9.69,13.74,14.58,19.44,20.66,25.35,29.33,29.66, wherein 2 θ value error ranges are ± 0.2.The preparation method of novel crystal forms provided by the invention is simple for process, and stability is high, is suitable for various forms preparation.
Description
Technical field
The invention belongs to medicinal chemistry arts, and in particular to 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl]
Piperazine hydrobromide alpha-crystal form and 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal and two
The preparation method of kind crystal form.
Background technology
Major depressive disorder patient will appear the vain hope of pessimistic and worldweary, desperate, illusion, loss of appetite, hypofunction and with tight
The conamen or even suicide of weight.It constitutes a serious threat to human health, therefore, it is necessary to pay much attention to, treats in time.
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide, which is considered as passing through
Inhibit serotonin transporter, and Active Regulation is carried out to 5-HT receptor subtypes and plays antidepressant effect.
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide chemical reaction it is as follows：
Invention content
The purpose of the present invention is to provide 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide
Alpha-crystal form and 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal and two kinds of crystal forms preparation
Method.
The present invention is used with 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine and hydrobromic acid at salt,
α, beta crystal are obtained under felicity condition, and are converted to beta crystal from alpha-crystal form.Raw material is easy to get, simple for process, high income, is suitble to work
Industry metaplasia is produced.
4- [2- of the present invention（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form,
It is characterized in that：In the powder x-ray diffraction collection of illustrative plates for the use of radiation source being Cu-K α, in 2 θ=5.81 ± 0.2,7.04 of the angle of diffraction
± 0.2,9.23 ± 0.2,14.10 ± 0.2,16.30 ± 0.2,17.49 ± 0.2,18.21 ± 0.2,18.58 ± 0.2,20.51
There is characteristic peak at ± 0.2,21.20 ± 0.2,22.98 ± 0.2,28.12 ± 0.2,31.49 ± 0.2 degree.
4- [2- of the present invention（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal,
It is characterized in that：In the powder x-ray diffraction collection of illustrative plates for the use of radiation source being Cu-K α, in 2 θ=6.86 ± 0.2,9.69 of the angle of diffraction
± 0.2,13.74 ± 0.2,14.58 ± 0.2,19.44 ± 0.2,20.66 ± 0.2,25.35 ± 0.2,29.33 ± 0.2,29.66
There is characteristic peak at ± 0.2 degree.
4- [2- of the present invention（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form
Preparation method, the preparation method include the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolved is in solvent；
(b) solution that filtration step (a) obtains, and after filtrate is cooled to 0-10 DEG C, after hydrobromic acid is added in heat preservation, drop finishes,
Continue insulated and stirred 1 hour；
(c) mixture after the insulated and stirred of filtration step (b), obtains filter cake 1, after the eluent solvent of the filter cake 1, control
0-10 DEG C of cleaning solution temperature, agitator treating 0.5 hour；
(d) mixture after the agitator treating of filtration step (c), obtains filter cake 2, after the eluent solvent of the filter cake 2, in 40-
It is dried in vacuo 12h at 50 DEG C, obtains 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form.
Above-mentioned solvent is following a kind of or arbitrary several combination：Water；Alcohols：Such as methanol, ethyl alcohol, normal propyl alcohol, isopropyl
Alcohol, n-butanol, sec-butyl alcohol, the tert-butyl alcohol, tertriary amylo alcohol, cyclohexanol, ethylene glycol, propylene glycol etc.；Ethers：Such as ether, isopropyl ether, methyl
Tertbutyl ether, butyl oxide, tetrahydrofuran, methyltetrahydrofuran, 1,4- dioxane etc.；Ketone：As acetone, butanone, methyl are different
Butanone, cyclohexanone etc.；Esters：Such as Ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isobutyl acetate
Deng；Alkanes：Such as petroleum ether, hexane, thiacyclohexane, heptane, toluene, dimethylbenzene, isopropylbenzene；Other aprotic solvents：Such as
N,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide (DMSO), nitromethane, acetonitrile etc..Preferably water, tetrahydrochysene furan
It mutters, acetone, ethyl alcohol, isopropanol, n-butanol, ethyl acetate, toluene or arbitrary several combination.
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] molar ratio of piperazine and hydrobromic acid is 1:0.90-1:
2, more preferable molar ratio is 1:0.99-1:1.2.
4- [2- of the present invention（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide β crystal
Preparation method, the preparation method include the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolved in solvent, be heated to all it is molten
Solution；
(b) after the solution that filtration step (a) obtains, after hydrobromic acid aqueous solution is added, continue stirring 1 hour；
(c) it after stirring 2h or more, filters and obtains filter cake 1, after the eluent solvent of the filter cake 1, agitator treating 1 hour；
(d) filtration step (c) obtains filter cake 2, and the filter cake 2 is dried in vacuo 12h at 60-70 DEG C, obtains 4- [2-（2- first
Base -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal.
Above-mentioned solvent is following a kind of or arbitrary several combination：Water；Alcohols：Such as methanol, ethyl alcohol, normal propyl alcohol, isopropyl
Alcohol, n-butanol, sec-butyl alcohol, the tert-butyl alcohol, tertriary amylo alcohol, cyclohexanol, ethylene glycol, propylene glycol etc.；Ethers：Such as ether, isopropyl ether, methyl
Tertbutyl ether, butyl oxide, tetrahydrofuran, methyltetrahydrofuran, 1,4- dioxane etc.；Ketone：As acetone, butanone, methyl are different
Butanone, cyclohexanone etc.；Esters：Such as Ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isobutyl acetate
Deng；Alkanes：Such as petroleum ether, hexane, thiacyclohexane, heptane, toluene, dimethylbenzene, isopropylbenzene；Other aprotic solvents：Such as
N,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide (DMSO), nitromethane, acetonitrile etc..Preferably water, tetrahydrochysene furan
It mutters, acetone, ethyl alcohol, isopropanol, n-butanol, ethyl acetate, toluene or arbitrary several combination.
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] molar ratio of piperazine and hydrobromic acid is 1:0.90-1:
2, more preferable molar ratio is 1:0.99-1:1.2.
4- [2- of the present invention（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form turn
The preparation method for becoming beta crystal includes the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form and solvent be added to
In reaction bulb, 20 DEG C to return stirring；
(b) insulated and stirred 2 hours or more；
(c) it is cooled to room temperature, filters and obtains filter cake 1, it is dry after the eluent solvent of the filter cake 1, obtain 4- [2-（2- methyl-
Tri- deuterium methyl of 4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal.
Above-mentioned solvent is following a kind of or arbitrary several combination：Water；Alcohols：Such as methanol, ethyl alcohol, normal propyl alcohol, isopropyl
Alcohol, n-butanol, sec-butyl alcohol, the tert-butyl alcohol, tertriary amylo alcohol, cyclohexanol, ethylene glycol, propylene glycol etc.；Ethers：Such as ether, isopropyl ether, methyl
Tertbutyl ether, butyl oxide, tetrahydrofuran, methyltetrahydrofuran, 1,4- dioxane etc.；Ketone：As acetone, butanone, methyl are different
Butanone, cyclohexanone etc.；Esters：Such as Ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isobutyl acetate
Deng；Alkanes：Such as petroleum ether, hexane, thiacyclohexane, heptane, toluene, dimethylbenzene, isopropylbenzene；Other aprotic solvents：Such as
N,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide (DMSO), nitromethane, acetonitrile etc..Preferably water, tetrahydrochysene furan
It mutters, acetone, ethyl alcohol, isopropanol, n-butanol, ethyl acetate, toluene or arbitrary several combination.
4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] molar ratio of piperazine and hydrobromic acid is 1:0.90-1:
2, more preferable molar ratio is 1:0.99-1:1.2.
Description of the drawings
Fig. 1 is 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide nucleus magnetic hydrogen spectrum figure.
Fig. 2 is 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide mass spectrogram.
Fig. 3 is that embodiment 1 prepares 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide α
The X-ray powder diffraction figure of crystal form samples.
Fig. 4 is the 4- [2- prepared by embodiment 1（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide α
The DSC collection of illustrative plates of crystal form.
Fig. 5 is the 4- [2- prepared by embodiment 1（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide α
The TGA collection of illustrative plates of crystal form.
Fig. 6 is that embodiment 2 prepares 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide β
The X-ray powder diffraction figure of crystal form samples.
Fig. 7 is the 4- [2- prepared by embodiment 2（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide β
The DSC collection of illustrative plates of crystal form.
Fig. 8 is the 4- [2- prepared by embodiment 2（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide β
The TGA collection of illustrative plates of crystal form.
Fig. 9 is that embodiment 3 prepares 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide α
Crystal form turns the X-ray powder diffraction figure of beta crystal sample.
Figure 10 is the 4- [2- prepared by embodiment 3（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide β
The DSC collection of illustrative plates of crystal form.
Specific implementation mode
According to following embodiments, the present invention may be better understood.However, as it will be easily appreciated by one skilled in the art that real
The content for applying example description is merely to illustrate the present invention, without that should will not limit this hair described in detail in claims
It is bright.
Embodiment 1：
By 10 g 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolved in 100 mL ethyl acetate,
30 DEG C of 20- stirring, which filters, obtains filtrate, and after filtrate is cooled to 0-10 DEG C, and 43% hydrobromic acid aqueous solution, 2.4 g is added dropwise in heat preservation,
Drop finishes, and continues insulated and stirred 1 hour；Filtering, gained filter cake are eluted with 50 mL ethyl acetate, are filtered, 40 DEG C of vacuum drying of filter cake
12h obtains 4- [2-（2- methyl -4- deuteriums methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide 10.2g.
4- [2- obtained（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form product analysis
As shown in Figure 3.After testing, the fusing point that sample is made in above-described embodiment is 223-226 DEG C.
Embodiment 2：
By 10 g 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolved in 100 mL ethyl acetate,
After 70 DEG C of stirring and dissolvings of 50-, 43% hydrobromic acid aqueous solution, 2.4 g is added dropwise in heat preservation, and drop finishes, after insulated and stirred is stayed overnight；It is slowly dropped to
Room temperature filters, obtains filter cake, washed with 50 mL ethyl acetate, filters, and 70 DEG C of vacuum drying 8h of filter cake obtain 4- [2-（2-
Three deuterium methyl of methyl -4--benzene sulfydryl）Phenyl] 10.1 g of piperazine hydrobromide.
4- [2- obtained（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal product analysis
As shown in Figure 6.After testing, the fusing point that sample is made in above-described embodiment is 231-234 DEG C.
Embodiment 3：
By 10 g 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form and 100 mL it is anhydrous
Ethyl alcohol is added in reaction bulb, is heated to 50 DEG C, insulated and stirred is overnight.It is down to room temperature, is filtered, absolute ethyl alcohol washing, filter cake 60
DEG C vacuum drying 12h, obtain 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] 8.1 g of piperazine hydrobromide.
4- [2- obtained（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal product analysis
As shown in Figure 9.After testing, the fusing point that sample is made in above-described embodiment is 231-234 DEG C.
Claims (10)
1. a kind of 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form, it is characterised in that：
In the powder x-ray diffraction collection of illustrative plates for the use of radiation source being Cu-K α, in 2 θ=5.81 ± 0.2,7.04 ± 0.2,9.23 of the angle of diffraction
± 0.2,14.10 ± 0.2,16.30 ± 0.2,17.49 ± 0.2,18.21 ± 0.2,18.58 ± 0.2,20.51 ± 0.2,
There is characteristic peak at 21.20 ± 0.2,22.98 ± 0.2,28.12 ± 0.2,31.49 ± 0.2 degree.
2. a kind of 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal, it is characterised in that：
In the powder x-ray diffraction collection of illustrative plates for the use of radiation source being Cu-K α, in 2 θ=6.86 ± 0.2,9.69 ± 0.2 of the angle of diffraction,
13.74 ± 0.2,14.58 ± 0.2,19.44 ± 0.2,20.66 ± 0.2,25.35 ± 0.2,29.33 ± 0.2,29.66 ± 0.2
There is characteristic peak at degree.
3. 4- [2- according to claim 1（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide α crystalline substances
Type, which is characterized in that the powder x-ray diffraction collection of illustrative plates of the alpha-crystal form is as shown in Figure 3.
4. 4- [2- according to claim 2（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide β crystalline substances
Type, which is characterized in that the powder x-ray diffraction figure of the beta crystal is as shown in Figure 6.
5. 4- [2- according to claim 1,（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide α
The preparation method of crystal form includes the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolves with solvent；
(b) solution that filtration step (a) obtains, and after filtrate is cooled to 0-10 DEG C, after hydrobromic acid is added, it is small to continue stirring 1
When；
(c) mixture of filtration step (b), obtains filter cake 1, after the eluent solvent of the filter cake 1, control washing in a solvent
0-10 DEG C of liquid temperature, agitator treating 0.5 hour；
(d) mixture of filtration step (c), obtains filter cake 2, and after the eluent solvent of the filter cake 2, vacuum is dry at 40-50 DEG C
It is dry, obtain three deuterated Vortioxetine hydrobromic acid salts.
6. according to the 4- [2- described in claims 2（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide β crystalline substances
The preparation method of type includes the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine dissolved in solvent, be heated to all it is molten
Solution；
(b) after hydrobromic acid being added, 20 DEG C to reflux are continued stirring 1 hour or more；
(c) it is down to room temperature, filters and obtains filter cake 1, after the eluent solvent of the filter cake 1, filter cake 1 is washed with stirring solvent；
(d) filtration step (c) obtains filter cake 2, and the filter cake 2 is dry at 50-70 DEG C, obtains 4- [2-（2- methyl -4- three
Deuterium methyl-benzene sulfydryl）Phenyl] piperazine hydrobromide crystal.
7. 4- [2- according to claim 1,（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide α
Crystal form can be transformed into beta crystal, and method includes the following steps：
(a) by 4- [2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide alpha-crystal form and solvent be added to
In reaction bulb, 20 DEG C to return stirring, preferably shorter than 20 DEG C of reflux temperature extremely flows back；
(b) insulated and stirred 2 hours or more, preferably 6 to 72 hours, more preferable 12 to 24 hours；
(c) it is cooled to room temperature, filters and obtains filter cake 1, it is dry after the eluent solvent of the filter cake 1, obtain 4- [2-（2- methyl-
Tri- deuterium methyl of 4--benzene sulfydryl）Phenyl] piperazine hydrobromide beta crystal.
8. being following a kind of or arbitrary several combination according to the solvent described in claim 5 or claim 6 or claim 7：
Water；Alcohols：As methanol, ethyl alcohol, normal propyl alcohol, isopropanol, n-butanol, sec-butyl alcohol, the tert-butyl alcohol, tertriary amylo alcohol, cyclohexanol, ethylene glycol,
Propylene glycol etc.；Ethers：Such as ether, isopropyl ether, methyl tertiary butyl ether(MTBE), butyl oxide, tetrahydrofuran, methyltetrahydrofuran, 1,4- bis-
Six ring of oxygen etc.；Ketone：Such as acetone, butanone, methylisobutylketone, cyclohexanone；Esters：Such as Ethyl formate, methyl acetate, acetic acid second
Ester, propyl acetate, butyl acetate, isobutyl acetate etc.；Alkanes：Such as petroleum ether, hexane, thiacyclohexane, heptane, toluene, diformazan
Benzene, isopropylbenzene etc.；Other aprotic solvents：As n,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide (DMSO),
Nitromethane, acetonitrile etc.；Preferably water, tetrahydrofuran, acetone, ethyl alcohol, isopropanol, n-butanol, ethyl acetate, toluene or arbitrary
Several combinations.
9. according to the 4- [2- described in claim 5（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine and hydrobromic acid rub
You are than being 1:0.90-1:2, more preferable molar ratio is 1:0.99-1:1.2.
10. according to the 4- [2- described in claim 6（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine and hydrobromic acid rub
You are than being 1:0.90-1:2, more preferable molar ratio is 1:0.99-1:1.2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710055758.9A CN108341793A (en) | 2017-01-25 | 2017-01-25 | 4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide novel crystal forms and preparation method |
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|---|---|---|---|
| CN201710055758.9A CN108341793A (en) | 2017-01-25 | 2017-01-25 | 4-[2-（Three deuterium methyl of 2- methyl -4--benzene sulfydryl）Phenyl] piperazine hydrobromide novel crystal forms and preparation method |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103788019A (en) * | 2014-01-22 | 2014-05-14 | 苏州明锐医药科技有限公司 | Preparation method of vortioxetine |
-
2017
- 2017-01-25 CN CN201710055758.9A patent/CN108341793A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103788019A (en) * | 2014-01-22 | 2014-05-14 | 苏州明锐医药科技有限公司 | Preparation method of vortioxetine |
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