CN109553603A - A kind of preparation method of antineoplaston medicine pomalidomide - Google Patents
A kind of preparation method of antineoplaston medicine pomalidomide Download PDFInfo
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- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 229960000688 pomalidomide Drugs 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000003814 drug Substances 0.000 title abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 11
- KFIRODWJCYBBHY-UHFFFAOYSA-N 3-nitrophthalic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1C(O)=O KFIRODWJCYBBHY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 238000009833 condensation Methods 0.000 claims abstract description 4
- 230000005494 condensation Effects 0.000 claims abstract description 4
- 238000006482 condensation reaction Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 3
- YCPULGHBTPQLRH-UHFFFAOYSA-N 3-aminopiperidine-2,6-dione;hydron;chloride Chemical compound Cl.NC1CCC(=O)NC1=O YCPULGHBTPQLRH-UHFFFAOYSA-N 0.000 claims abstract 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 13
- 229960000583 acetic acid Drugs 0.000 claims description 12
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 230000000259 anti-tumor effect Effects 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 6
- 229940040526 anhydrous sodium acetate Drugs 0.000 claims description 6
- 239000012362 glacial acetic acid Substances 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 229940126585 therapeutic drug Drugs 0.000 claims 6
- 238000006722 reduction reaction Methods 0.000 claims 3
- 239000002904 solvent Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- 239000012065 filter cake Substances 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000005360 mashing Methods 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 238000007605 air drying Methods 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 208000034578 Multiple myelomas Diseases 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- PEUGKEHLRUVPAN-UHFFFAOYSA-N piperidin-3-amine Chemical compound NC1CCCNC1 PEUGKEHLRUVPAN-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000004845 hydriding Methods 0.000 description 3
- 229960004942 lenalidomide Drugs 0.000 description 3
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000002584 immunomodulator Effects 0.000 description 2
- 229940008606 pomalyst Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- -1 3- amino Piperidine-2,6-diones hydrochloride Chemical class 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation methods of antineoplaston medicine pomalidomide, belong to pharmaceutical synthesis field.With 3- nitrophthalic acid and 3- amino piperidine -2,6- dione hydrochloride for raw material, pomalidomide is obtained after two steps such as condensation reaction, nitro reduction.The method that the present invention compares existing literature report, synthesis step is few, reaction condition is mild, easy to operate, and condensation step avoids the use of Heavy Metal Reagent and toxic organic solvents, Determination of Residual Organic Solvents is low, environmental-friendly, integrated artistic is more environmentally protective, and quality is easy to control, the advantages that technology stability is higher is suitble to industrialized production.
Description
Technical field
The present invention relates to technical field of medicine synthesis, and in particular to a kind of preparation side of antineoplaston medicine pomalidomide
Method.
Background technique
Pomalidomide Pomalyst, entitled 3- amino-N- (2, the 6- dioxo -3- piperidyl) phthalyl of chemistry are sub-
Amine, English entitled 3-Amino-N- (2,6-dioxo-3-piperidyl) phthalimide, No. CAS: 19171-19-8, property
Shape: light yellow solid, fusing point: 318.5 DEG C -320.5 DEG C, molecular formula: C13H11N3O4, molecular weight: 273.24, dissolubility: readily soluble
In DMSO.
Pomalidomide is the third generation immunomodulator (IMiD) after Thalidomide, lenalidomide, is treated other anti-
The multiple myeloma patients that are still in progress of the state of an illness after the treatment of cancer medicine show unique anti-infective, immunological regulation, antitumor
The effects of hyperplasia, anti-angiogenesis, and for refractory MM (RRMM) clinical test in show it is full of hope
Curative effect and relative to Thalidomide, the less toxic side effect of lenalidomide.It can enhance T cell and natural killer cells mediates
Immune response, while inhibit monocyte generate pro-inflammatory cytokine (such as TNF-α, IL-6).In addition, pomalidomide can
Inhibit tumor cell proliferation and induce cell apoptosis, also has stronger increasing to the drug resistant multiple myeloma cell line of lenalidomide
Grow inhibiting effect.2 months 2013 8 Nikkei U.S. food and Drug Administration's approval, pomalidomide in U.S.'s Initial Public Offering,
Trade name Pomalyst, it is small, significant in efficacy etc. with toxic side effect for treating recurrent and Refractory Multiple Myeloma
Advantage, market application prospect are wide.
Pomalidomide is the third generation immunomodulator developed by Celegene company, the U.S., is mainly used for treating multiple
Myeloma and myeloproliferative disorders.Therefore, economy, environmental-friendly is developed, the pomalidomide that can be mass produced
Synthesis route is of great practical significance.Therefore, on the basis of with reference to existing synthetic route, a work is studied
Skill mild condition is good, high production efficiency, low in input cost, operation is simple, is easy to industrial synthetic route just
It is very necessary, important data and technique preparation are added for the developing target market of pomalidomide at home, makes at home can its future
The large-scale production of competitiveness is enough provided, and is used widely.
Summary of the invention
In order to solve the deficiencies in the prior art, the present invention provides a kind of preparation sides of antineoplaston medicine pomalidomide
Method.
A kind of preparation method of antineoplaston medicine pomalidomide, which comprises the steps of: adjacent with 3- nitro
Phthalic acid 2 is raw material, by obtaining pomalidomide after the two-step reactions such as condensation reaction, nitro reduction.
Reaction equation is as follows:
Further, in the above-mentioned technical solutions, the condensation step is, by 3- nitrophthalic acid 2 and 3- amino
Piperidine-2,6-diones hydrochloride 3 is condensed to yield compound 4 under the conditions of glacial acetic acid and anhydrous sodium acetate.
Further, in the above-mentioned technical solutions, the 3- nitrophthalic acid 2 and 3- amino piperidine -2,6- diketone
3 equivalent proportion of hydrochloride is 1.5-2.5:1.It is preferably in a proportion of 2:1.
Further, the nitro reduction step is that compound 4 adds under DMF/ acetic acid in the mixed solvent, palladium carbon catalysis
Hydrogen reacts to obtain pomalidomide.Preferably, the nitro reduction step be will be dissolved in compound 4 DMF/ acetic acid mixing it is molten
In agent, under palladium carbon catalysis, 30-40 DEG C of reaction temperature, Hydrogen Vapor Pressure 2.5-3.5MPa, reaction obtains pomalidomide 1.Wherein,
Palladium carbon is selected from 5% or 10% palladium carbon, and additional amount is 0.02-0.08 times of 4 weight of compound.
Further, the product pomalidomide is recrystallized to give 99.5% or more sterling of purity by dimethyl sulfoxide.
Advantageous effect of the invention:
1, compared to the method for existing literature report, condensation step avoids making for Heavy Metal Reagent and toxic organic solvents
With Determination of Residual Organic Solvents is low, and environmental-friendly, integrated artistic is more environmentally protective.
2, pomalidomide is after dimethyl sulfoxide recrystallizes, the product of available 99.5% or more purity.
3, synthesis step of the present invention is few, and reaction condition is mild, easy to operate, and convenient post-treatment, technology stability is higher, matter
Amount is easy to control, and is more suitable for industrialized production.
Specific embodiment
Embodiment 1
3- nitrophthalic acid 2 (4.22g, 20.0mmol), 3- amino piperidine -2,6- diketone are added in three-necked bottle
Hydrochlorate 3 (1.64g, 10mmol) and 16mL glacial acetic acid, are heated to 105-115 DEG C, and the anhydrous sodium acetate of 5g, control reaction temperature is added
105-115 DEG C of degree reacts 3-4h.Reaction solution is cooled to 80-90 DEG C, is filtered, filter cake is beaten with water and is washed, and drains, filter cake is used
The dissolution of 18mL n,N-Dimethylformamide, is added 1.5g active carbon, stirs 0.5h, filters, and 350mL water, stirring are instilled in filtrate
2-3h is filtered, and the mashing of filter cake water washes twice, and is drained, by solid in 50-60 DEG C of forced air drying 20-24h, is obtained 2.70g chemical combination
Object 4, yield: 89%.
Take compound 4 (3.03g, 10.0mmol) to be dissolved in 120mL n,N-Dimethylformamide, be added 4mL acetic acid and
0.14g 10%Pd/C is transferred to hydriding reactor, is kept for 30-40 DEG C of reacting liquid temperature, Hydrogen Vapor Pressure 2.5-3.5MPa, reacts 10-
12h, HPLC detect reaction end.Reaction terminates, and diatomite filters off palladium carbon, and 1.2g active carbon is added in filtrate, stirs 0.5h, takes out
It filters, 46mL pure water is added in filtrate, stir 1-2h, filter, the mashing of filter cake water washes twice, 50-60 DEG C of forced air drying 10-
12h obtains 2.59g pomalidomide crude product, yield: 95%.
Pomalidomide method for recrystallizing and refining: pomalidomide crude product (2.73g, 10mmol) is taken to be dissolved in 45mL dimethyl sulfoxide
In, 20-25 DEG C of stirring and dissolving filters off insoluble matter, instills 165mL methanol, stirring and crystallizing 3-4h in filtrate.It filters, filter cake 70-
80 DEG C of pure water mashing are washed 2-3 times, drain, solid is obtained light yellow solid (compound in 50-60 DEG C of vacuum drying 10-12h
1) 2.56g, yield 94%, HPLC: purity 99.55%.Mp:319-322 DEG C.ESI-MS m/z:274.1[M+H]+,
296.1[M+Na]+。1H-NMR (400MHz, DMSO-d6):2.03-2.89(m,4H),5.05-5.09(m,1H),6.54(s,
2H), 7.02 (t, 2H, J=8.0Hz), 7.48 (t, 1H, J=7.6Hz), 11.10 (s, 1H).
Embodiment 2
3- nitrophthalic acid 2 (42.2g, 200.0mmol), 3- amino piperidine -2,6- diketone are added in three-necked bottle
Hydrochloride 3 (16.4g, 100mmol) and 80mL glacial acetic acid, are heated to 105-115 DEG C, and the anhydrous sodium acetate of 50g is added, and control is anti-
105-115 DEG C of temperature is answered, 3-4h is reacted.Reaction solution is cooled to 80-90 DEG C, is filtered, filter cake is beaten with water and is washed, and is drained, will be filtered
Cake 180mL n,N-Dimethylformamide dissolves, and 15g active carbon is added, and stirs 0.5h, filters, and 500mL water is instilled in filtrate,
2-3h is stirred, is filtered, the mashing of filter cake water washes twice, and drains, by solid in 50-60 DEG C of forced air drying 20-24h, obtains 27.1g
Compound 4, yield: 89%.
Take compound 4 (30.3g, 100.0mmol) to be dissolved in 800mLN, in dinethylformamide, be added 300mL acetic acid and
1.4g 10%Pd/C is transferred to hydriding reactor, is kept for 30-40 DEG C of reacting liquid temperature, Hydrogen Vapor Pressure 2.5-3.5MPa, reacts 10-12h,
HPLC detects reaction end.Reaction terminates, and diatomite filters off palladium carbon, and 12g active carbon is added in filtrate, stirs 0.5h, filters, filter
800mL pure water is added in liquid, stirs 1-2h, filters, the mashing of filter cake water washes twice, and 50-60 DEG C of forced air drying 10-12h is obtained
25.94g pomalidomide crude product, yield: 95%.
Pomalidomide method for recrystallizing and refining: pomalidomide crude product (27.3g, 100mmol) is taken to be dissolved in 900mL dimethyl sulfoxide
In, 20-25 DEG C of stirring and dissolving filters off insoluble matter, instills 300mL methanol, stirring and crystallizing 3-4h in filtrate.It filters, filter cake 70-
80 DEG C of pure water mashing are washed 2-3 times, are drained, and solid is obtained light yellow solid pool Ma Du in 50-60 DEG C of vacuum drying 10-12h
Amine 25.6g, yield 94%, HPLC: purity 99.62%.Mp:319-322 DEG C.ESI-MS m/z:274.1[M+H]+,
296.1[M+Na]+。1H-NMR(400MHz,DMSO-d6):2.03-2.89(m,4H),5.05-5.09(m,1H),6.54(s,
2H), 7.02 (t, 2H, J=8.0Hz), 7.48 (t, 1H, J=7.6Hz), 11.10 (s, 1H).
Embodiment 3
3- nitrophthalic acid 2 (4.22kg, 20.0mol), 3- amino piperidine -2,6- diketone are added in three-necked bottle
Hydrochlorate 3 (1.64kg, 10mol) and 16L glacial acetic acid are heated to 105-115 DEG C, and 500g anhydrous sodium acetate, control reaction temperature is added
105-115 DEG C of degree reacts 3-4h.Reaction solution is cooled to 80-90 DEG C, is filtered, filter cake is beaten with water and is washed, and drains, filter cake is used
The dissolution of 18L n,N-Dimethylformamide, is added 550g active carbon, stirs 0.5h, filters, and 35L water is instilled in filtrate, stirs 2-
3h is filtered, and the mashing of filter cake water washes twice, and is drained, by solid in 50-60 DEG C of forced air drying 20-24h, is obtained 2.73kg chemical combination
Object 4, yield: 90%.
It takes compound 4 (3.03kg, 10.0mol) to be dissolved in 12L n,N-Dimethylformamide, 4L acetic acid and 140g is added
10%Pd/C is transferred to hydriding reactor, is kept for 30-40 DEG C of reacting liquid temperature, Hydrogen Vapor Pressure 2.5-3.5MPa, reacts 10-12h, HPLC
Detect reaction end.Reaction terminates, and diatomite filters off palladium carbon, and 1.2kg active carbon is added in filtrate, stirs 0.5h, filters, filtrate
Middle addition 46L pure water stirs 1-2h, filters, and the mashing of filter cake water washes twice, and 50-60 DEG C of forced air drying 10-12h is obtained
2.62kg pomalidomide crude product, yield: 96%.
Pomalidomide method for recrystallizing and refining: taking pomalidomide crude product (2.73kg, 10mol) to be dissolved in 45L dimethyl sulfoxide,
20-25 DEG C of stirring and dissolving filters off insoluble matter, instills 1.65L methanol, stirring and crystallizing 3-4h in filtrate.It filters, filter cake 70-80
It the mashing of DEG C pure water washing 2-3 times, drains, solid is obtained into light yellow solid pomalidomide in 50-60 DEG C of vacuum drying 10-12h
2.57kg, yield 94%HPLC: purity 99.78%.Mp:319-322 DEG C.ESI-MS m/z:274.1[M+H]+, 296.1
[M+Na]+。1H-NMR(400MHz,DMSO-d6): 2.03-2.89 (m, 4H), 5.05-5.09 (m, 1H), 6.54 (s, 2H), 7.02
(t, 2H, J=8.0Hz), 7.48 (t, 1H, J=7.6Hz), 11.10 (s, 1H).
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (6)
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| CN114605381A (en) * | 2020-12-03 | 2022-06-10 | 南京海辰药业股份有限公司 | Preparation method of pomalidomide |
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| CN103819454A (en) * | 2014-03-13 | 2014-05-28 | 南京华威医药科技开发有限公司 | Preparation method of N-(2, 6-dioxo-3-piperidyl) phthalimide compound |
| CN104926786A (en) * | 2014-03-21 | 2015-09-23 | 合肥久诺医药科技有限公司 | Method for preparing 3-nitro-N-(2,6-dioxo-3-piperidinyl) phthalimide |
| CN105348257A (en) * | 2014-08-20 | 2016-02-24 | 河北菲尼斯生物技术有限公司 | Pomalidomide preparation method |
| CN104387366A (en) * | 2014-10-30 | 2015-03-04 | 南京恒通医药开发有限公司 | Preparation method of pomalidomide |
| CN107325075A (en) * | 2016-04-29 | 2017-11-07 | 正大天晴药业集团股份有限公司 | A kind of preparation method of pomalidomide |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114605381A (en) * | 2020-12-03 | 2022-06-10 | 南京海辰药业股份有限公司 | Preparation method of pomalidomide |
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