CN106831608A - A kind of novel crystal forms of compound and preparation method and application - Google Patents
A kind of novel crystal forms of compound and preparation method and application Download PDFInfo
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- CN106831608A CN106831608A CN201710083678.4A CN201710083678A CN106831608A CN 106831608 A CN106831608 A CN 106831608A CN 201710083678 A CN201710083678 A CN 201710083678A CN 106831608 A CN106831608 A CN 106831608A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
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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
Abstract
The invention discloses a kind of anti-HIV new medicament molecule 3 { [3 ethyl 2,6 dioxy 5 (base of the propyl group 2) base of 1,2,3,6 tetrahydropyrimidine 4] carbonyl } 5 methyl cyanophenyl I crystals, the invention also discloses the preparation method of above-mentioned I crystal.The DSC collection of illustrative plates of the crystal formation has endothermic peak at 227 ± 1.5 DEG C, and melting range is 223~231 DEG C.The crystal formation have excellent stability, beneficial to post processing and store；And preparation method is simple, optimization and exploitation to follow-up related drugs have important value.
Description
Technical field
The invention belongs to pharmaceutical chemistry, more particularly to a kind of novel crystal forms of compound and preparation method and application.
Background technology
Currently without the cure method infected for inhibition of HIV.The mid-90 in 20th century, efficient anti-retroviral is treated
The appearance of method (highly active antiretroviral therapy, HAART) be considered as in treating AIDS history in
The event of journey upright stone tablet.HAART be used in combination it is several can block or suppress inhibition of HIV enter born of the same parents, duplication, transcription, translation, assembling etc.
The antiretroviral drugs of process, so as to fully suppress the propagation of virus, reality are reduced to by the virus load in the infected's body
(≤50 copies/ml) are tested below the detection level of room, function of immune system is allowed to and is obtained a certain degree of recovery, finally significantly delayed
The progress of disease, substantially reduces the incidence of disease and case fatality rate of AIDS, while reducing the propagation of HIV.In recent years, HIV was reversed
Transcriptase inhibitors have become the medicine that an important class is controlled and treats HIV.So far, U.S. FDA approval is anti-
HIV medicines have kind more than 20, are broadly divided into six major classes：Nucleosides (acid) class RTI (nucleoside/
Nucleotide reverse transcriptase inhibitors, N (t) RTI), non-nucleoside reverse transcriptase inhibitor
(non-nucleoside reverse transcriptase inhibitors, NNRTI), protease inhibitors (PI), fusion
Inhibitor, integrase chain tra nsfer inhibitor (INSTI) and accessory receptor inhibitor.Just control the preferred antiviral therapy of AIDS patient
Scheme is combined a kind of NNRTI or PI or INSTI and constitute again by 2 kinds of N (t) RTI at present, and the guide that DHHS is issued was since 2009 years
List 4 kinds of such therapeutic schemes：1. tenofovir+emtricitabine+efavirenz；2. tenofovir+emtricitabine+Da Runa
Wei/Ritonavir；3. tenofovir+emtricitabine+atazanavir/Ritonavir；4. tenofovir+emtricitabine+Lei Tege
Wei.
3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- methyl
Cyanophenyl, is a kind of new non-nucleoside reverse transcriptase inhibitor, can be used for inhibition of HIV infection mitigation and treatment, and its English is entitled
3-[[3-ethyl-1,2,3,6-tetrahydro-5-(1-methylethyl)-2,6-dioxo-4-pyrimidinyl]
Carbonyl] -5-methyl benzonitrile, its chemical structural formula such as following formula：
Molecular formula：C18H19N3O3Molecular weight：325.14
No. CAS of the compound is 1097628-00-6, is once included with code name：GS9441 (Gilid Science Co.),
KM023 (Kaino Medicine) and ACC007 (Jiangsu Ai Di pharmaceutcal corporation, Ltds).
United States Patent (USP) US2009/0163712 A1 report the synthetic process of the compound, and partial reaction is operated again
It is optimized, can be used for industrialized production, production cost is relatively low, can meet active demand of the China to inverase.It but is used for
Prepare the active material crystallization of medical composition, it should with high-purity and high stability, even if in harsher condition of storage
Under, stabilization should be also kept, also need to ensure that the crystal habit will not change in prepared by subsequent preparation and store.So far it is
Only, the result of study report of its related crystal formation is had no.
The content of the invention
It is an object of the invention to provide a kind of 3- { [3- ethyl -2,6- dioxies -5- with high-purity and high stability
(propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- methyl cyanophenyl I crystals.
The present invention also aims to provide above-mentioned 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6-
Tetrahydropyrimidine -4- bases] carbonyl -5- methyl cyanophenyl I crystals preparation method with application.
A kind of 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -4- of the present invention
Base] carbonyl -5- methyl cyanophenyl I crystals, the X-ray powder diffraction collection that the crystal formation is represented with 2 θ angles as shown in Figure 1,
Following position has characteristic peak：6.6±0.1°,8.3±0.1°,10.7±0.1°,12.6±0.1°,13.3±0.1°,15.1
±0.1°,16.6±0.1°,17.6±0.1°,19.0±0.1°,19.6±0.1°,20.1±0.1°,20.5±0.1°,21.7
±0.1°,22.2±0.1°,23.5±0.1°,24.0±0.1°,24.7±0.1°,25.4±0.1°,26.9±0.1°,27.9
±0.1°,28.7±0.1°,30.3±0.1°,38.2±0.1°。
The X-ray powder diffraction data of such as crystal formation of accompanying drawing 2 are visible, 3- { [3- ethyl -2,6- dioxies -5- of the invention
(propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- methyl cyanophenyl I crystal X-ray powder diffraction spectrum, also
Show multiple characteristic absorption peaks.
The DSC collection of illustrative plates of the compound I crystal at 227 ± 1.5 DEG C as shown in figure 3, have endothermic peak.
The melting range of the compound I crystal is 223~231 DEG C.
The preparation method of above-claimed cpd I crystal, comprises the following steps：Take 3- [3- ethyl -2,6- dioxies -5- (propyl group -
2- yls) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- methyl cyanophenyl crude products, organic solvent is added, solvent refluxing is heated to,
And stir certain hour；0 DEG C~35 DEG C and keeping temperature are cooled to, stirring growing the grain is complete to crystallization；It is then peeled off and collects crystalline substance
Body, is drying to obtain I crystal.
The dissolving heating-up temperature is solvent reflux temperature；Mixing time is 0.5~10h, is preferably 1~2h.
The organic solvent be selected from isopropanol, ethanol, acetonitrile and ethyl acetate in one or more.
Preferably, the organic solvent is ethanol or isopropanol.Most preferably ethanol.
3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] the carbonyl } -5-
The mass volume ratio of methyl cyanophenyl crude product and organic solvent is 1:3~1:10.
Preferably, described 3- { [3- ethyl -2, the tetrahydropyrimidine -4- bases of 6- dioxies -5- (propyl group -2- bases) -1,2,3,6-]
Carbonyl } mass volume ratio of -5- methyl cyanophenyl crude products and organic solvent is 1:5~1:7.
The unit of above-mentioned mass volume ratio refers to that, when mass unit is g, volume unit is mL, when mass unit is kg, body
Product unit is L.
Lower the temperature after dissolving using natural cooling or logical condensation water cooling, condensate temperature is -10 DEG C~25 DEG C.
Growing the grain temperature is 0~35 DEG C, preferably 20~25 DEG C；Rearing crystal time is 0.5~5h, preferably 1~2h.
Growing the grain to crystallization uses vacuum filtration or centrifugation afterwards completely.
Described dry using air blast or vacuum drying, drying temperature is 40 DEG C~80 DEG C, preferably 60~65 DEG C；When drying
Between be 30~60h, preferably 40~50h.
3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] of the present invention
Carbonyl } -5- methyl cyanophenyl crystal formation I, and the pharmaceutical composition containing the crystallization, can be used for the prevention of various HIV persons and
Treatment.
Beneficial effect：The invention provides a kind of anti-HIV new medicament molecule (3- { [3- ethyl -2,6- dioxies -5- (propyl group -2-
Base) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl -5- methyl cyanophenyl) I crystal, the crystal formation have excellent stability,
Beneficial to post processing and storage；And preparation method is simple, can be used to prepare the medicine of AntiHIV1 RT activity, the optimization to follow-up related drugs
There is important value with exploitation.
Brief description of the drawings
Fig. 1 is 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The X-ray powder diffraction representativeness spectrogram of methyl cyanophenyl crystal formation I；
Fig. 2 is 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The X-ray powder diffraction representativeness spectral data of methyl cyanophenyl crystal formation I；
Fig. 3 is 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The DSC representativeness spectrograms of methyl cyanophenyl crystal formation I.
Specific embodiment
The present invention is explained in detail with reference to specific embodiment.
Reagent source：
3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- methyl
Cyanophenyl crude product is purchased from Sangdiya Pharmaceutical Technology (Shanghai) CLC, and crude product is detected using HPLC area normalization methods, pure
Degree is not less than 98%.
Embodiment 1：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I preparation
Take 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- first
Base cyanophenyl crude product 20g adds 60mL isopropanols in reaction bulb, is heated to backflow, insulated and stirred 10h；Side is stirred, the logical condensation in side
Water is cooled to 0 DEG C, continues insulated and stirred 0.5h, and vacuum filtration, filter cake is vacuum dried 60h, obtains 19g off-white powders in 80 DEG C,
Purity 99.3%, yield 95%.
To preparing gained 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I carried out powder x-ray diffraction analysis, its X-ray powder diffraction spectrogram and representative spectrogram one
Cause, as shown in Figure 1；X-ray powder diffraction data are consistent with representative spectral data, as shown in Figure 2；DSC collection of illustrative plates and representativeness
Spectrogram is consistent, as shown in Figure 3.
Embodiment 2：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I preparation
Take 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- first
Base cyanophenyl crude product 200g adds 1200ml ethanol in reaction bulb, is heated to backflow, 4~5h of insulated and stirred；Side is stirred, Bian Tong
Condensed water is cooled to 25 DEG C, continues insulated and stirred 1.5h, and vacuum filtration, filter cake is vacuum dried 48h, obtains 144g classes in 60~65 DEG C
White solid, purity 99.57%, yield 72%.
To preparing gained 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I carried out powder x-ray diffraction analysis, its X-ray powder diffraction spectrogram and representative spectrogram one
Cause, as shown in Figure 1；X-ray powder diffraction data are consistent with representative spectral data, as shown in Figure 2；DSC collection of illustrative plates and representativeness
Spectrogram is consistent, as shown in Figure 3.
Embodiment 3：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I preparation
Take 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- first
Base cyanophenyl crude product 200g adds 2000ml acetonitriles in reaction bulb, is heated to backflow, and stirring is to molten clear；Side is stirred, and side drops naturally
Temperature continues insulated and stirred 5h to 35 DEG C, and centrifugation, filter cake obtains 128g off-white powders, purity in 40 DEG C of forced air drying 30h
99.30%, yield 64%.
To preparing gained 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I carried out powder x-ray diffraction analysis, its X-ray powder diffraction spectrogram and representative spectrogram one
Cause, as shown in Figure 1；X-ray powder diffraction data are consistent with representative spectral data, as shown in Figure 2；DSC collection of illustrative plates and representativeness
Spectrogram is consistent, as shown in Figure 3.
Embodiment 4：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I preparation
Take 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- first
Base cyanophenyl crude product 200g is added in 1000mL ethanol in reaction bulb, is heated to backflow, stirs 1.5h；Side is stirred, and side drops naturally
Temperature continues insulated and stirred 1.5h to 25 DEG C, and centrifugation, filter cake is vacuum dried 60h, obtains 156g off-white colors at 60~65 DEG C
Solid, purity 99.56%, yield 78%.
To preparing gained 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I carried out powder x-ray diffraction analysis, its X-ray powder diffraction spectrogram and representative spectrogram one
Cause, as shown in Figure 1；X-ray powder diffraction data are consistent with representative spectral data, as shown in Figure 2；DSC collection of illustrative plates and representativeness
Spectrogram is consistent, as shown in Figure 3.
Embodiment 5：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I thermal stability determination
Example 1-3 prepares gained 3-, and { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydrochysenes are phonetic
Pyridine -4- bases] carbonyl } -5- methyl cyanophenyl crystal formation I, at 50~60 DEG C, 70~80 DEG C, at 90~100 DEG C, 48h is dried, and to drying
Sample purity is tested after dry, and experimental result is as shown in table 1.
The 3- of table 1 { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The heat endurance of methyl cyanophenyl
Result shows, under 50~100 DEG C of drying temperature, the content of this product does not have significant changes, steady quality.
Embodiment 6：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formation I acceleration environment Stability Determination
The storage that crystal formation I obtained by being prepared to embodiment 1,2,3 has carried out under acceleration environment, to 0 day sample melting range and molten
Point has carried out capillary tube method and the detection of DSC methods, and the melting range after accelerating 6 months has carried out capillary tube method detection, as shown in table 2.
The 3- of table 2 { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The stability of methyl cyanophenyl crystal formation I acceleration environments
Result shows that after three batches of samples place 6 months under acceleration conditions, fusing point and melting range do not occur significant changes,
This product is proved with this understanding, with good stability.
Embodiment 7：3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyls
Base } -5- methyl cyanophenyl crystal formations I Assay of Antiviral Activity
3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- as obtained by 5 days multi cycle test method(s)s have detected embodiment 4
Base) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } the antiviral work of -5- methyl cyanophenyl crystal formation I in MT-2, MT-4 cell line
Property, as shown in table 3.
The 3- of table 3 { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5-
The antiviral activity of methyl cyanophenyl crystal formation I
SD=standard deviation (standard deviation)；EC50=half-maximal effective
Concentration (medium effective concentration)；CC50(half is thin for=half-maximal cytotoxic concentration
Born of the same parents' poison concentration)
aN (number of independent experiments) (independent experiment number) >=10.
b N≥4.
c N≥3.
It is visible according to testing result, its antiviral efficacy, the EC determined in MT-2 cells50It is 6.8nM to be worth, thin in MT-4
In born of the same parents, EC50It is 7.6nM to be worth, under equivalent assay conditions, 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6-
Tetrahydropyrimidine -4- bases] carbonyl } antiviral activity of -5- methyl cyanophenyl crystal formations I is slightly below efavirenz (Efavirenz), but its
Cytotoxicity is low compared with efavirenz.Therefore, this product has excellent antiviral activity, and with good security.
Claims (10)
1. a kind of 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidine -4- bases] carbonyl } -5- first
Base cyanophenyl I crystal, it is characterised in that the X-ray powder diffraction collection that the compound I crystal is represented with 2 θ angles is with bottom
Put with characteristic peak：6.6±0.1°,8.3±0.1°,10.7±0.1°,12.6±0.1°,13.3±0.1°,15.1±0.1°,
16.6±0.1°,17.6±0.1°,19.0±0.1°,19.6±0.1°,20.1±0.1°,20.5±0.1°,21.7±0.1°,
22.2±0.1°,23.5±0.1°,24.0±0.1°,24.7±0.1°,25.4±0.1°,26.9±0.1°,27.9±0.1°,
28.7±0.1°,30.3±0.1°,38.2±0.1°。
2. 3- according to claim 1 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl } -5- methyl cyanophenyl I crystals, it is characterised in that the DSC collection of illustrative plates of the crystal formation has heat absorption at 227 ± 1.5 DEG C
Peak.
3. { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydrochysenes are phonetic for 3- according to claim 1 and 2
Pyridine -4- bases] carbonyl } -5- methyl cyanophenyl I crystals, it is characterised in that the melting range of the crystal formation is 223~231 DEG C.
4. 3- { [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -4- described in claim 1 or 2
Base] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that comprise the following steps：Take 3- { [3- ethyls -2,6-
Tetrahydropyrimidine -4- the bases of dioxy -5- (propyl group -2- bases) -1,2,3,6-] carbonyl } -5- methyl cyanophenyl crude products, organic solvent is added, plus
Heat stirs certain hour to solvent refluxing；0 DEG C~35 DEG C and keeping temperature are cooled to, stirring growing the grain is complete to crystallization；Then
Crystal is separated and collected, I crystal is drying to obtain.
5. 3- according to claim 4 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that the organic solvent be selected from isopropanol, ethanol,
One or more in acetonitrile and ethyl acetate.
6. 3- according to claim 4 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that described crude product and the mass body of organic solvent
Product is than being 1:3~1:10.
7. 3- according to claim 4 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that described heating-up temperature be solvent reflux temperature,
Described mixing time is 0.5h~10h；Cooling is using natural cooling or logical condensation water cooling；Growing the grain to crystallization it is complete after, adopt
With vacuum filtration or centrifugation.
8. 3- according to claim 4 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that rearing crystal time be 0.5~5h.
9. 3- according to claim 4 [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyl I crystals preparation method, it is characterised in that it is described it is dry use air blast or vacuum drying, do
Dry temperature is 40 DEG C~80 DEG C, and drying time is 30~60h.
10. described in claim 1 or 2 3- [3- ethyl -2,6- dioxies -5- (propyl group -2- bases) -1,2,3,6- tetrahydropyrimidines -
4- yls] carbonyl -5- methyl cyanophenyls I crystal be used for prepare AntiHIV1 RT activity medicine application.
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| CN112113809A (en) * | 2020-06-29 | 2020-12-22 | 扬州工业职业技术学院 | Method for measuring content of anti-argyi drugs by using ultrasonic emulsification-suspension solvent curing microextraction UV |
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