CN106496187A - A kind of synthetic method for preparing PARP inhibitor Niraparib - Google Patents
A kind of synthetic method for preparing PARP inhibitor Niraparib Download PDFInfo
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Abstract
A kind of new synthetic method for preparing PARP inhibitor Niraparib, the method include with initiation material methyl anthranilate that through diazo coupling cyclization, amidatioon, de- BOC, chiral resolution obtain the Niraparib that purity reaches 99.5%.The inventive method is easy, it is easy to operates, is a method which be suitable for industrial production.
Description
Technical field
The invention belongs to technical field of medicine synthesis, is related to a kind of synthetic method for preparing PARP inhibitor Niraparib.
Background technology
Niraparib is a kind of oral Poly ADP-ribose polymerase (PARP) inhibitor, can suppress cell to DNA damage
Reparation, it is adaptable to cancer of BRCA1/2 gene mutations, such as oophoroma and breast cancer etc., by biotech company of the U.S.
Tesaro is researched and developed.For the cancer cell with BRCA gene mutations, if PARP activity is further suppressed, these are thin
Born of the same parents will produce a large amount of DNA damages when dividing, and cause cancer cell death.Niraparib chemical names are 2- [4- ((3S) -3- piperazines
Piperidinyl) phenyl] -2H- indazole -7- formamides, the III clinical trial phases that a key name is NOVA have been completed, Niraparib represents
Extremely good curative effect.In test, researcher has recruited the trouble of more than 500 oophoroma appearance recurrence after platinum-based chemotherapy
Person, and patient has been divided into two groups according to reproduction cell whether with BRCA gene mutations.It is mutated with BRCA in reproduction cell
Group in, through Niraparib treatment patient's progression free survival phase median be up to 21 months, than 5.5 of control group
The moon has obtained notable prolongation.
At present, for the relevant patent document of the synthetic method of Niraparib includes Preparation in prior art
of pharmaceutically acceptable salts of(3S)-3-[4-[7-(aminocarbonyl)-2H-
indazol-2-yl]phenyl]piperid ines as inhibitors of poly(ADP-ribose)polymerase
(PARP), Preparation of piperidinylphenylindazolylcarboxamide for use as poly
(ADP-ribose) polymerase inhibitors etc., it is disclosed that a chemical synthesis route, as follows and right
The discovery procedure of Niraparib has carried out detailed discussion.
The synthetic route with 3- methyl -2- nitrobenzoic acids as initiation material, by with methyl alcohol under conditions of acyl chlorides ester
Change and obtain compound A, A is heated to reflux 12 hours in CCl4 solution of the benzoyl peroxide with NBS, and bromination obtains compound B.B with
Acetonitrile and the oxidation of N-methylmorpholine-N- oxide water solutions obtain compound C.The compound C and tert-butyl group -3- (4- aminophenyls)
Piperidines -1- carboxylic acid tert-butyl esters are stirred at reflux in ethanol solution and obtain compound D.Compound D and sodium azide and DMF mixtures
Reaction, cyclization formed intermediate E .. compound E be passed through in methanol solution 60 DEG C of NH3 heating acylated intermediate F. compounds
F adds hydrochloric acid in ethyl acetate with dioxane solution, sloughs BOC groups and obtains intermediate G, through Chiralpak AS-H positives
Chiral chromatographic column splits and obtains target compound S type rotamer Niraparib.The synthetic route is longer, uses
Chiralpak AS-H positive chiral chromatographic columns split Niraparib is difficult to realize large-scale industrial production, and in reacting
The raw material of the unstable and difficult post processing such as sodium azide has been used, industrialization safety in production has been limited.
Content of the invention
In order to overcome the above-mentioned deficiencies of the prior art, the purpose of the present invention is to improve one kind to prepare PARP inhibitor
The synthetic method of Niraparib, route are novel, obtain multiple brand-new intermediates, and the property of intermediate in building-up process
Stable, easy to operate, it is easy to accomplish industrialized production.
To achieve these goals, of the invention realize that process is as follows：
A kind of synthetic method for preparing PARP inhibitor Niraparib, synthetic route are as follows：
,
Wherein compound (I) is PARP inhibitor Niraparib.
The following specifically describes synthesis step：
The first step：
Methyl anthranilate is mixed with sulfuric acid solution, then is slowly added dropwise natrium nitrosum, -10 DEG C of reaction temperature to 10
DEG C, with the tert-butyl group -3- Phenylpiperidine -1- t-butyl formates in 10% sodium hydroxide solution environment after the brownish red diazol of generation
In carry out coupling reaction and obtain intermediate (II), intermediate (II) structure is
Second step:
Intermediate (II) is in ten carbonyls, two rhenium [Re2(CO)10] and the catalysis of sodium acetate [NaOAc] under, catalytic intermediary
(II) azobenzene structure cyclization, cyclization in the dicyandiamide solution of methyl alcohol form indazole ring, obtain intermediate (III), realize one
The indazole structure that constructs in intermediate (III) is walked, the structure of intermediate (III) is
3rd step：
Intermediate (III) is added sodium methoxide, formamide after being dissolved in dry DMF at 0 DEG C, 40 DEG C of reactions are warming up to
3.5h, forms the amide structure in intermediate (IV), obtains crude intermediate (IV) after methyl esters ammonolysis, then at room temperature by crude product
Intermediate (IV) is added to dioxane-water (volume ratio 8：1) in mixed solvent, 101 DEG C are warming up to, solid molten rear addition entirely
Activated carbon, backflow, suction filtration, filtrate, stand, suction filtration while hot, dry, obtain intermediate (IV), and the structure of intermediate (IV) is：
4th step:
Intermediate (IV) with the de- BOC protection groups of trifluoroacetic acid reaction, makees solvent, thing with dichloromethane in dichloromethane
The mol ratio of matter is intermediate (IV)：Dichloromethane：Trifluoracetic acid=1: 5: 1, reaction in about 3 hours is stirred at room temperature completely, is evaporated
Racemization intermediate (V) is obtained, and the structure of intermediate (V) is
5th step：
Racemization intermediate (V) is dissolved in backflow dissolving in organic solvent, L- (+)-tartaric acid is added, crystallization of lowering the temperature is separated
Solid crystal, obtains Niraparib.L- (+)-tartrate, is dissolved in water, and hydro-oxidation sodium solution alkalizes, then
Ethyl acetate extraction is added, washing is drying to obtain compound (I) PARP inhibitor Niraparib, and its structural formula isDescribed organic solvent is 10～20 with the mass ratio of racemization intermediate (V):1；Described
L- (+)-tartaric acid is 0.5～5 with the mass ratio of Niraparib intermediates 4:1, preferably 3～4:1.
The organic solvent used during racemization intermediate (V) chemical resolution in the 5th described step is tetrahydrofuran, first
Alcohol, ethanol, acetone, ethyl acetate or several arbitrary proportion mixtures, preferred alcohol, ethyl acetate, recrystallization temperature are -10～0
℃.
Take off in the 4th described step BOC protection reactions prepare solvent used by racemization intermediate (V) selected from tetrahydrofuran, two
One or more in six ring of oxygen, dichloromethane, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, acetonitrile are appointed
Meaning scalemic thereof mixture, preferably dichloromethane, it is room temperature to take off the used temperature of BOC.
In the described first step by methyl anthranilate prepare diazol can use potassium nitrite, calcium nitrite,
Silver nitrite, natrium nitrosum, barium nitrite, nitrous ether (ethyl nitrite), isoamyl nitrite, isobutyl nitrite, Isopropyl Nitrite,
Nitrite tert-butyl, nitrous acid straight butyl, n-propyl nitrite are carried out as the reagent of diazo-reaction, preferably natrium nitrosum.
The present invention compared with prior art, this have the advantage that：
1) the initiation material methyl anthranilate that the present invention is adopted synthesizes the original that field generally adopts for organic drug
Material, low price and is readily obtained；
2) synthetic route of the present invention is short, and step is simple.
3) present invention in each intermediate link only with such as：The operations such as extraction, dry, filtration, crystallization and recrystallization
Method, post processing are simple and convenient, are easier to realize large-scale production；
4) route of the present invention is novel, obtains multiple brand-new intermediates in building-up process, and intermediate is stable in properties,
Easy to operate, it is easy to accomplish industrialized production.
Description of the drawings
Fig. 1 is the HPLC chromatogram of final thing Niraparib of the present invention.
Specific embodiment
With reference to embodiments the present invention is further discussed below, but the present invention is not limited to following examples.
Embodiment
Intermediate (II)Synthesis, the synthesis of intermediate (II) is divided into two steps
Carry out, the preparation of first step diazol：By 52mL (0.4mol) methyl anthranilate and 20% sulfuric acid of 170mL
(0.62mol) mix, when being cooled to 10 DEG C, 42mL 30% natrium nitrosum (0.4mol) solution is slowly added dropwise in reaction bulb.With
The excessive nitrous acid of starch potassium iodide paper inspection, determines reaction end.The brownish red diazol of generation carries out second step and uncle
The coupling reaction of butyl -3- Phenylpiperidine -1- t-butyl formates：Take 100g (0.4mol) tert-butyl group -3- Phenylpiperidine -1- formic acid
The tert-butyl ester is dissolved in 10% sodium hydroxide solutions of 500mL, is stirred continuously in the above-mentioned diazol of lower instillation, stirs 5h, stand knot
Crystalline substance, suction filtration, and recrystallize in ethanol 127g intermediate (II), yield：78%.
1H-NMR(400MHz,DMSO-d6)(ppm)δ:8.50 (2H, q, J=7.5Hz,
J=7.6Hz) 8.25 (1H, d, J=8.1Hz) 8.19 (1H, q, J=7.5Hz, J=7.6Hz), 8.11 (1H, d, J
=8.1Hz) 7.86 (1H, q, J=7.6Hz, J=7.5Hz), 7.50 (2H, q, J=7.6Hz, J=7.5Hz), 3.89 (3H, s),
3.62 (2H, d, J=8.2Hz), 3.34 (2H, d, J=8.2Hz), 2.78 (1H, m), 1.79 (2H, m), 1.48 (2H, m), 1.38
(9H,s)；13C-NMR(75MHz,DMSO-d6)δ(ppm):164.3,153.7,149.9,
141.3,133.3,128.4,127.8,122.8,116.9,79.8,57.0,49.0,40.5,30.5,28.4,
22.7；HRMS(ESI)for(M+H)+:calcd:407.22,found:408.22
Intermediate (III)Synthesis, take 82g (0.2mol) Niraparib
Intermediate 1 is mixed with 68mL (0.64mol) toluene and 16mL (0.4mol) methyl alcohol, stirring and dissolving, adds ten carbonyls of 6.5g, two rhenium
([Re2(CO)10] 10mmol) and 5.4g sodium acetates (0.04mol) as catalyst, be heated to reflux 72 hours at 150 DEG C, while hot
Filter, static crystallization, 40 DEG C of vacuum drying 4h obtain 51.2g intermediates (III), and yield is 61%.
1H NMR(400MHz,CDCl3, 300K) and d 8.51 (1H, s), 8.13 (1H, d, J=7.1Hz), 7.95 (1H, d),
7.91 (2H, d, J=8.4Hz), 7.39 (2H, d, J=8.4Hz), 7.18 (1H, t, J=7.1Hz), 4.30-4.10 (2H, m),
4.00(3H,s),2.85-2.70(3H,m),2.11-2.03(1H,m),1.83-1.75(1H,m),1.73-1.53(2H,m),
1.48(9H,s).
13CNMR(75MHz,DMSO-d6)δ(ppm):167.1,153.2,145.6,136.9,128.7,124.3,120.6,
112.0,79.8,
57.0,51.5,49.0,40.5,30.5,28.4,22.7；HRMS(ESI)for(M+H)+:calcd:435.22,
found:436.22
Intermediate (IV)Synthesis, at 0 DEG C by the middle of 17.2g (41mmol)
Body (III) is dissolved in 100mL dry DMFs, adds 13mL (328mmol) formamide, 3.3g (62mmol) methyl alcohol in this solution
Sodium, is warming up to 40 DEG C of reaction 3.5h.Reactant liquor is cooled to room temperature, is poured in 400mL water, stir 1h, suction filtration is dried, in obtaining
Mesosome (IV) crude product 17.23g (theoretical yield is 13.78g), yield is 87%.3 crude product 10.0g of compound is added under room temperature
To in the mixed solvent of 80mL dioxane-water (volume ratio 8: 1), 101 DEG C are warming up to, solid is entirely molten to add 0.2g (quality afterwards
Fraction 2%) activated carbon, continues backflow 0.5h, while hot suction filtration, and filtrate is cooled to 0 DEG C, stands 2h (precipitation white needle-like crystals),
Suction filtration, dries, obtains intermediate (IV).
1H NMR(400MHz,CDCl3, 300K) and d 9.04 (1H, br.s), 8.51 (1H, s), 8.31 (1H, d, J=
8.3Hz), 7.91 (1H, d, J=8.3Hz), 7.84 (2H, d, J=8.2Hz), 7.42 (2H, d, J=8.2Hz), 7.31-7.22
(1H,m),5.95(1H,br.s),4.40-4.05(2H,m),2.90-2.70(3H,m),2.15-2.00(1H,m),1.85-
1.75(1H,m),1.75-1.50(2H,m),1.48(9H,s).13CNMR(75M Hz,DMSO-d6)δ(ppm):168.0,
153.2,143.2,136.9,128.7,126.7,125.0,124.1,120.8,115.0,79.8,57.0,49.0,
30.5,40.5,28.4,22.7,HRMS(ESI)for(M+H)+:calcd:420.22,found:421.22
Intermediate (V)Synthesis, 18g intermediates (IV) (42mmol) are added
To in 180mL dichloromethane, after being sufficiently mixed, 50mL trifluoroacetic acid solutions are gradually added dropwise, after stirring 24h, 80mL hydrogen-oxygens is added
Change sodium water solution, stratification collects organic phase, with anhydrous sodium sulfate drying, reduced pressure concentration obtains 11.2g intermediates (V), mole
Yield is 83.33%.
1H NMR(400MHz,DMSO-d6,300K)d 9.32(1H,s),9.12(1H,br.s),8.87(1H,br.s),
8.55 (1H, br.s), 8.13 (2H, d, J=8.6Hz), 8.06 (1H, J=7.0Hz), 8.02 (1H, d, J=8.4Hz), 7.89
(1H, br.s), and 7.55 (2H, d, J=8.6Hz), 7.27 (1H, dd, J=8.4,7.0Hz), 3.43-3.27 (2H, m), 3.17-
3.03(2H,m),3.00-2.85(1H,m),2.00-1.70(4H,m).13CNMR(75MHz,DMSO-d6)δ(ppm):168.0,
143.2,136.9,128.7,126.7,
124.1,120.8,115.0,52.4,48.6,
43.3,30.5,25.5.HRMS(ESI)for(M+H)+:calcd:320.16,found:321.16
Compound (I) NiraparibSynthesis, 100g intermediates (V) are added to
In 1000mL absolute ethyl alcohols, 50g L- (+)-tartaric acid for heating to back flow reaction 0.5h is added, system is cooled to -10 then～
0 DEG C of crystallization, is filtrated to get solid；Solid is refined with 200mL ethyl alcohol recrystallizations, L- (+)-tartaric acid of Niraparib is obtained
Salt 66.89g, molar yield 45.5%.
The L- (+) of Niraparib-tartrate 4.5g is added in 22.5mL pure water, is then added under the conditions of normal temperature water-bath
Enter sodium hydroxide solution 1.3g, after being sufficiently mixed, add ethyl acetate 45.0mL, 3h is stirred at room temperature to clarification.Stratification, water
Mutually extracted with 45.0mL ethyl acetate again, merge organic phase；Washed with 15mL water and saturated nacl aqueous solution 15mL successively, with nothing
Aqueous sodium persulfate is filtered after drying, and filtrate is concentrated into dilute crystalline substance, obtains compound (I) Niraparib 2.88g, the step after crystal is dried
The yield 94.2% of reaction, overall yield of reaction is 14.78%, and it is 99.5% to determine compound (I) Niraparib purity through HPLC
(chromatogram is illustrated in fig. 1 shown below), using Daicel companyAD-3 150mm × 2.1mm chiral columns are measured
Ee values are 99.7%.1H-NMR(400MHz,DMSO-d6,300K)d 8.52(1H,s),8.17(1H,br,d),8.03(1H,d,
), J=7.2Hz 7.66 (1H, q, J=8.4Hz),
7.54 (2H, t), 7.50 (2H, br.s), 7.30 (2H, d, J=8.4Hz),
3.15-2.90(2H,d),2.78(1H,m),
2.76-2.73(2H,t),2.0(1H,m),1.92-1.67(2H,q),1.53-1.43(2H,m).13C-NMR
(75MHz,DMSO-d6)
δ(ppm):168.0,143.2,136.9,128.7,126.7,125.0,124.1,115.0,52.4,43.3,
48.6,30.5,25.5,
HRMS(ESI)for(M+H)+:calcd:352.14,found:353.14.
Claims (9)
1. a kind of synthetic method for preparing PARP inhibitor Niraparib, synthetic route are as follows：
,
Wherein compound (I) is PARP inhibitor Niraparib.
2. a kind of synthetic method for preparing PARP inhibitor Niraparib according to right 1, it is characterised in that by adjacent ammonia
Yl benzoic acid methyl esters is mixed with sulfuric acid solution, then is slowly added dropwise natrium nitrosum, -10 DEG C to 10 DEG C of reaction temperature, generation reddish brown
Carry out being coupled instead after color diazol with the tert-butyl group -3- Phenylpiperidine -1- t-butyl formates in 10% sodium hydroxide solution environment
Deserved intermediate (II), intermediate (II) structure is
3. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that in
Mesosome (II) is in ten carbonyls, two rhenium (Re2(CO)10) and the catalysis of sodium acetate (NaOAc) under, the azobenzene of catalytic intermediary (II)
Structure cyclization, cyclization in the dicyandiamide solution of methyl alcohol form indazole ring, obtain intermediate (III), realize that a step constructs intermediate
(III) the indazole structure in, the structure of intermediate (III) is
4. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that 0
DEG C intermediate (III) is added sodium methoxide, formamide after be dissolved in dry DMF, be warming up to 40 DEG C of reaction 3.5h, methyl esters ammonolysis
Form the amide structure in intermediate (IV) afterwards, obtain crude intermediate (IV), then at room temperature crude intermediate (IV) is added
Enter to dioxane-water (volume ratio 8：1) in mixed solvent, 101 DEG C are warming up to, solid is entirely molten to add activated carbon afterwards, flows back,
Suction filtration, filtrate, stand, suction filtration while hot, dry, obtain intermediate (IV), and the structure of intermediate (IV) is：
5. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that in
Mesosome (IV) with the de- BOC protection groups of trifluoroacetic acid reaction, makees solvent, the mol ratio of material with dichloromethane in dichloromethane
For intermediate (IV)：Dichloromethane：Trifluoracetic acid=1: 5:1, reaction in about 3 hours is stirred at room temperature completely, is evaporated
Intermediate (V), the structure of intermediate (V) is
6. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that will
Racemization intermediate (V) is dissolved in backflow dissolving in organic solvent, adds L- (+)-tartaric acid, crystallization of lowering the temperature, and separates solid crystal, obtains
To Niraparib.L- (+)-tartrate, it is dissolved in water, hydro-oxidation sodium solution alkalizes, and then adds acetic acid second
Ester is extracted, and washing, reduced pressure concentration are drying to obtain compound (I) PARP inhibitor Niraparib, and its structural formula isThe mass ratio of described organic solvent and Niraparib racemization intermediates (V) is 10～
20:1；Described L- (+)-tartaric acid is 0.5～5 with the mass ratio of Niraparib racemization intermediates (V):1.
7. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that institute
The organic solvent used during racemization intermediate (V) chemical resolution in the 5th step that states be tetrahydrofuran, methyl alcohol, ethanol, third
Ketone, ethyl acetate or several arbitrary proportion mixtures, preferred alcohol, ethyl acetate, recrystallization temperature are -10～0 DEG C.
8. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that institute
Take off in the 4th step that states BOC protection reactions prepare solvent used by racemization intermediate (V) selected from tetrahydrofuran, dioxane, two
One or more arbitrary proportions in chloromethanes, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, acetonitrile are mixed
Polymer mixtures, preferably dichloromethane, it is room temperature to take off the used temperature of BOC.
9. a kind of synthetic method for preparing PARP inhibitor Niraparib according to claim 1, it is characterised in that institute
Preparing diazol and can use potassium nitrite, calcium nitrite, silver nitrite, Asia by methyl anthranilate in the first step that states
The tertiary fourth of sodium nitrate, barium nitrite, nitrous ether (ethyl nitrite), isoamyl nitrite, isobutyl nitrite, Isopropyl Nitrite, nitrous acid
Ester, nitrous acid straight butyl, n-propyl nitrite are carried out as the reagent of diazo-reaction.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018183354A1 (en) * | 2017-03-27 | 2018-10-04 | Tesaro, Inc. | Niraparib compositions |
| WO2018200517A1 (en) * | 2017-04-24 | 2018-11-01 | Tesaro, Inc. | Methods of manufacturing of niraparib |
| CN109134351A (en) * | 2018-09-21 | 2019-01-04 | 武汉理工大学 | S-3-(4- aminophenyl) piperidines synthetic method |
| CN110156751A (en) * | 2019-05-28 | 2019-08-23 | 江苏食品药品职业技术学院 | A kind of new method preparing Ni Lapani and its intermediate |
| CN110343088A (en) * | 2019-07-17 | 2019-10-18 | 东南大学 | A kind of derivative and its preparation method and application based on PARP inhibitor Niraparib |
| US20210347758A1 (en) * | 2018-10-03 | 2021-11-11 | Tesaro, Inc. | Crystalline Forms of Niraparib Freebase |
| US11730725B2 (en) | 2017-09-26 | 2023-08-22 | Tesaro, Inc. | Niraparib formulations |
| US12005057B2 (en) | 2018-05-22 | 2024-06-11 | Tesaro, Inc. | Methods of treating ovarian cancer |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0700432D0 (en) * | 2007-01-10 | 2007-02-21 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
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| TWI761476B (en) * | 2017-03-27 | 2022-04-21 | 美商提薩羅有限公司 | Niraparib compositions |
| US20200017462A1 (en) | 2017-03-27 | 2020-01-16 | Tesaro, Inc. | Niraparib compositions |
| US11091459B2 (en) | 2017-03-27 | 2021-08-17 | Tesaro, Inc. | Niraparib compositions |
| US11673877B2 (en) | 2017-03-27 | 2023-06-13 | Tesaro, Inc. | Niraparib compositions |
| WO2018183354A1 (en) * | 2017-03-27 | 2018-10-04 | Tesaro, Inc. | Niraparib compositions |
| US11629137B2 (en) | 2017-04-24 | 2023-04-18 | Tesaro, Inc. | Methods of manufacturing of niraparib |
| CN110753684A (en) * | 2017-04-24 | 2020-02-04 | 特沙诺有限公司 | Method for producing nilapali |
| US11161834B2 (en) | 2017-04-24 | 2021-11-02 | Tesaro, Inc. | Methods of manufacturing of niraparib |
| WO2018200517A1 (en) * | 2017-04-24 | 2018-11-01 | Tesaro, Inc. | Methods of manufacturing of niraparib |
| US11730725B2 (en) | 2017-09-26 | 2023-08-22 | Tesaro, Inc. | Niraparib formulations |
| US12005057B2 (en) | 2018-05-22 | 2024-06-11 | Tesaro, Inc. | Methods of treating ovarian cancer |
| CN109134351A (en) * | 2018-09-21 | 2019-01-04 | 武汉理工大学 | S-3-(4- aminophenyl) piperidines synthetic method |
| CN109134351B (en) * | 2018-09-21 | 2022-03-11 | 武汉理工大学 | Synthesis method of S-3- (4-aminophenyl) piperidine |
| US20210347758A1 (en) * | 2018-10-03 | 2021-11-11 | Tesaro, Inc. | Crystalline Forms of Niraparib Freebase |
| CN110156751A (en) * | 2019-05-28 | 2019-08-23 | 江苏食品药品职业技术学院 | A kind of new method preparing Ni Lapani and its intermediate |
| CN110343088A (en) * | 2019-07-17 | 2019-10-18 | 东南大学 | A kind of derivative and its preparation method and application based on PARP inhibitor Niraparib |
| CN110343088B (en) * | 2019-07-17 | 2021-05-11 | 东南大学 | Derivative based on PARP inhibitor Niraparib and preparation method and application thereof |
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