CN109535035A - A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester - Google Patents
A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester Download PDFInfo
- Publication number
- CN109535035A CN109535035A CN201910015050.XA CN201910015050A CN109535035A CN 109535035 A CN109535035 A CN 109535035A CN 201910015050 A CN201910015050 A CN 201910015050A CN 109535035 A CN109535035 A CN 109535035A
- Authority
- CN
- China
- Prior art keywords
- benzyloxycarbonyl group
- butyl ester
- asparagine
- tert
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester, low, the at high cost technical problem of total recovery in original process is mainly solved.Preparation method of the present invention is the following steps are included: the first step, asparagine is suspended in the mixed liquor of water and acetone, adjusting pH value with sodium carbonate liquor is alkalinity, benzyl chloroformate, then temperature reaction is added in cooling, after completely reacted, it is acidified with hydrochloric acid, solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration；Second step, N- benzyloxycarbonyl group asparagine are suspended in methylene chloride, are passed through isobutene, enriching sulfuric acid, and sealing reaction two days handles, obtains the N- benzyloxycarbonyl group asparagine tert-butyl ester；Third step, the N- benzyloxycarbonyl group asparagine tert-butyl ester are dissolved in water and n,N-Dimethylformamide, and iodobenzene diacetate is added, first reacts and pyridine is added afterwards, and the reaction was continued to after terminating, and obtain final products through processing.
Description
Technical field
The present invention relates to a kind of preparation methods of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester.
Background technique
N- benzyloxycarbonyl group -3- amino-alanine the tert-butyl ester is a kind of important intermediate of organic synthesis, liquid phase synthesis polypeptide
Also it is commonly used and arrives.The general preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester are as follows: N- benzyloxycarbonyl group -3- amino
Alanine obtains N- benzyloxycarbonyl group -3- amino alanine tert-butyl ester through isobutene and strong sulfuric acid response, is loaded in document label chemical combination
Object and radiopharmaceutical magazine [Hamill, Terence G.; Askew, Ben C.; Hartman, George D.;
Claremon, David A.; McIntyre, Charles J.; Burns, H. Donald;Journal of
Labelled Compounds and Radiopharmaceuticals; vol. 41; nb. 4; (1998); p. 273 -
277] in, yield 75%；Also it is loaded in document biological organic and pharmaceutical chemistry flash report [Egbertson; Bednar; Hartman;
Gould; Lynch; Vassallo; Young; Bioorganic and Medicinal Chemistry Letters;
vol. 6; nb. 12;(1996);P. 1415-1420] in, yield 64%.But intermediate N benzyloxycarbonyl group -3- amino-the third
The propylhomoserin market price is expensive, because synthesis obtains high-purity N- benzyloxycarbonyl group -3- amino-alanine yield 50% or so.
The existing N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester the preparation method comprises the following steps:
The first step, asparagine are suspended in the mixed liquor of water and acetone, adjust pH value with the sodium carbonate liquor of mass fraction 20%
Between 8-9, cool to 0 DEG C, benzyl chloroformate or benzyloxy carbonyl acyl succinimide be added, be then warming up to 10-20 DEG C it
Between react, after completely reacted, be acidified to pH=1 with the hydrochloric acid of 4 equivalents, solid be precipitated, intermediate N benzyloxycarbonyl group day is obtained by filtration
Winter amide, yield 90%；
Second step, intermediate N benzyloxycarbonyl group asparagine are dissolved in water and n,N-Dimethylformamide, and iodobenzene diacetate is added,
Pyridine is added after 15 minutes in reaction, and normal-temperature reaction is overnight, filters solid, is washed twice with ethyl acetate, obtain crude product N- benzyloxy carbonyl
Base -3- amino-alanine obtains highly finished product N- benzyloxycarbonyl group -3- amino-alanine, yield by crude product by soda acid crystal system
50%;
Third step, N- benzyloxycarbonyl group -3- amino alanine are suspended in dioxane, and isobutene is added and the concentrated sulfuric acid seals room temperature
Reaction obtains N- benzyloxycarbonyl group -3- amino alanine tert-butyl ester, yield 64-75%；For total recovery in 28.8-33.75%, yield is inclined
It is low, cause at high cost.
Summary of the invention
The technology of the present invention aims to overcome that yield is low in original process, problem at high cost, provides a kind of N- benzyloxy carbonyl
The preparation method of the base -3- amino-alanine tert-butyl ester, this method is simple and easy to control, high income, at low cost, is suitable for scale
Production.
In order to achieve the above object of the invention, the technical solution adopted by the present invention is that: a kind of N- benzyloxycarbonyl group -3- amino-the third
The preparation method of the propylhomoserin tert-butyl ester, which comprises the following steps:
The first step, asparagine are suspended in the mixed liquor of water and acetone, and adjusting pH value with sodium carbonate liquor is alkalinity, are cooled down,
Benzyl chloroformate is added, then temperature reaction after completely reacted, is acidified with hydrochloric acid, and solid is precipitated, intermediate N benzyl is obtained by filtration
Oxygen carbonyl asparagine；
Second step, N- benzyloxycarbonyl group asparagine are suspended in methylene chloride, are passed through isobutene, enriching sulfuric acid, sealing reaction two
It, processing obtains the N- benzyloxycarbonyl group asparagine tert-butyl ester；
Third step, the N- benzyloxycarbonyl group asparagine tert-butyl ester are dissolved in water and n,N-Dimethylformamide, and iodobenzene diacetate is added,
It first reacts and pyridine is added afterwards, the reaction was continued to after terminating, and obtains final products N- benzyloxycarbonyl group -3- the-the third ammonia of amino through processing
Tert-butyl acrylate.
Specific step is as follows: the first step, and asparagine is suspended in the mixed liquor of water and acetone, and mass fraction is used in stirring
20% sodium carbonate liquor adjusts pH value between 8-9, cools to 0 DEG C, and benzyl chloroformate is added, and keeps temperature less than 3 DEG C, 1 ~ 2
Hour adds, and is then warming up between 18-20 DEG C and reacts, and reacts 10 hours.TLC detection, raw material reaction terminates, with 4 equivalents
Hydrochloric acid is acidified to pH=1, and solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration, and dries, yield about 90%.Asparagus fern
Amide, water, acetone, the mass ratio of benzyl chloroformate are 1:10:(2 ~ 3): (1.5 ~ 1.8)；
Second step, N- benzyloxycarbonyl group asparagine are suspended in methylene chloride, and stirring cools down T < -5 DEG C, is passed through isobutene, are added dropwise
The concentrated sulfuric acid of mass fraction 98%, natural temperature reaction after adding.N- benzyloxycarbonyl group asparagine, methylene chloride, isobutene are dense
The mass ratio of sulfuric acid are as follows: 1:(15 ~ 20): (1.5 ~ 2): 0.1.Sealing normal-temperature reaction two days, is washed with saturated sodium bicarbonate aqueous solution
It washs twice, is concentrated under reduced pressure and removes methylene chloride, obtain the N- benzyloxycarbonyl group asparagine tert-butyl ester, yield 95%；
Third step, the N- benzyloxycarbonyl group asparagine tert-butyl ester are suspended in water and n,N-Dimethylformamide, and oxalic acid iodine is added
Pyridine is added after 15 minutes in benzene, reaction, and the reaction was continued 4 hours.Reaction terminate after, reaction system with acidified with citric acid to pH=
Ethyl acetate extraction is added in 3-4, and ethyl acetate washed with water is washed once, and salt washing is primary, is concentrated under reduced pressure into the one of original volume
Half, petroleum ether crystallization is added, obtains the final products N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester.N- benzyloxycarbonyl group asparagus fern acyl
The amine tert-butyl ester, water, n,N-Dimethylformamide, iodobenzene diacetate, pyridine, ethyl acetate, the mass ratio of petroleum ether are as follows: 1:20:
10:(1.4 ~ 1.5): 0.25:20:20.Yield 85-90%.Total recovery 72.68-76.95%.
The beneficial effects of the present invention are: common method be first by N- benzyloxycarbonyl group asparagine after Hoffmann rearrangement reaction
N- benzyloxycarbonyl group -3- amino alanine is obtained, then the tert-butyl ester, but this process overall yields are low.And the method for the present invention is first
N- benzyloxycarbonyl group asparagine is esterified to obtain the N- benzyloxycarbonyl group asparagine tert-butyl ester, then rearranged reaction obtains most
Finished product, the rearrangement reaction yield of the N- benzyloxycarbonyl group asparagine tert-butyl ester improve the process overall yields in 85-90%.Pass through
Change Product Process, production cost can be significantly reduced.
Detailed description of the invention
Fig. 1 is 1 final products MS map of the embodiment of the present invention.
Fig. 2 is 1 final products HPLC map of the embodiment of the present invention.
Fig. 3 is 1 final products nuclear magnetic spectrogram of the embodiment of the present invention.
Fig. 4 is 1 final products infared spectrum of the embodiment of the present invention.
Specific embodiment
The present invention includes but is not limited to following examples
Embodiment 1:
10KG asparagine is suspended in the mixed liquor of 100KG water and 25KG acetone by the first step, stirring, with mass fraction 20%
Sodium carbonate liquor adjust pH value between 8-9, cool to 0 DEG C, be slowly added to benzyl chloroformate 16KG, keep temperature less than 3
DEG C, it adds within 1 hour, is then warming up between 18-20 DEG C and reacts, react 10 hours.TLC detection, raw material reaction terminate, are worked as with 4
The hydrochloric acid of amount is acidified to pH=1, and solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration, and dries, obtains solid
18.14KG yield 90%.
Second step, 18.14KG N- benzyloxycarbonyl group asparagine are suspended in 330KG methylene chloride, stirring, and cool down T < -5
DEG C, it is passed through isobutene 33KG, the concentrated sulfuric acid 1.81KG of mass fraction 98% is added dropwise, natural temperature reaction after adding.It is anti-to seal room temperature
It answers two days, is washed twice with saturated sodium bicarbonate aqueous solution, be concentrated under reduced pressure and remove methylene chloride, obtain grease N- benzyloxycarbonyl group
Asparagine tert-butyl ester 20.86KG, yield 95%；
Third step, the 20.86KG grease N- benzyloxycarbonyl group asparagine tert-butyl ester are suspended in 417.2KG water and 208.6KG N, N-
In dimethylformamide, iodobenzene diacetate 30.5KG is added, 5.215KG pyridine is added after reaction 15 minutes, it is 4 small that the reaction was continued
When.TLC monitoring, after reaction terminates, the extraction of 417.2KG ethyl acetate is added in reaction system acidified with citric acid to pH=3-4,
Ethyl acetate washed with water is washed once, and salt washing is primary, is concentrated under reduced pressure into the half of original volume, and 417.2KG petroleum ether knot is added
Crystalline substance, filtering, drying obtain final products N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester 16.76KG, white solid, yield
87.98%.Total recovery 75.22%.Product MS map is shown in that Fig. 1, product HPLC map are shown in that Fig. 2, product nuclear magnetic spectrogram are shown in Fig. 3, product
Infared spectrum is shown in Fig. 4.
Embodiment 2
100G asparagine is suspended in the mixed liquor of 1000G water and 300G acetone by the first step, stirring, with mass fraction 20%
Sodium carbonate liquor adjust pH value between 8-9, cool to 0 DEG C, be slowly added to benzyl chloroformate 150G, keep temperature less than 3
DEG C, it adds within 1 ~ 2 hour, is then warming up between 18-20 DEG C and reacts, react 10 hours.TLC detection, raw material reaction terminates, with 4
The hydrochloric acid of equivalent is acidified to pH=1, and solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration, and dries, obtains solid
182G, yield 90.3%.
Second step, 182G N- benzyloxycarbonyl group asparagine are suspended in 2730G methylene chloride, and stirring cools down T < -5 DEG C,
It is passed through isobutene 364G, the concentrated sulfuric acid 18.2G of mass fraction 98% is added dropwise, natural temperature reaction after adding.Seal normal-temperature reaction two
It, is washed twice with saturated sodium bicarbonate aqueous solution, is concentrated under reduced pressure and is removed methylene chloride, obtains grease N- benzyloxycarbonyl group asparagus fern
Amide tert-butyl ester 209.34G, yield 95%；
Third step, the 209.34G grease N- benzyloxycarbonyl group asparagine tert-butyl ester are suspended in 4186.8G water and 2093.4G N, N-
In dimethylformamide, iodobenzene diacetate 314.01G is added, 52.34G pyridine is added after reaction 15 minutes, it is 4 small that the reaction was continued
When.TLC monitoring, after reaction terminates, the extraction of 4186.8G ethyl acetate is added in reaction system acidified with citric acid to pH=3-4,
Ethyl acetate washed with water is washed once, and salt washing is primary, is concentrated under reduced pressure into the half of original volume, and 4186.8G petroleum ether knot is added
Crystalline substance, filtering, drying obtain final products N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester 172.0G, white solid, yield
90.0%.Total recovery 77.21%. product map is shown in embodiment 1.
Embodiment 3
2KG asparagine is suspended in the mixed liquor of 20KG water and 4KG acetone by the first step, stirring, with mass fraction 20%
Sodium carbonate liquor adjusts pH value between 8-9, cools to 0 DEG C, is slowly added to benzyl chloroformate 3.6KG, keeps temperature less than 3
DEG C, it adds within 2 hours, is then warming up between 18-20 DEG C and reacts, react 10 hours.TLC detection, raw material reaction terminate, are worked as with 4
The hydrochloric acid of amount is acidified to pH=1, and solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration, and dries, obtains solid
3.6KG, yield 89.3%.
Second step, 3.6KG N- benzyloxycarbonyl group asparagine are suspended in 72KG methylene chloride, and stirring cools down T < -5 DEG C,
It is passed through isobutene 5.4KG, the concentrated sulfuric acid 0.36KG of mass fraction 98% is added dropwise, natural temperature reaction after adding.Seal normal-temperature reaction
It two days, is washed twice with saturated sodium bicarbonate aqueous solution, is concentrated under reduced pressure and removes methylene chloride, obtain grease N- benzyloxycarbonyl group day
Winter amide tert-butyl ester 4.1KG, yield 94.0%；
Third step, the 4.1KG grease N- benzyloxycarbonyl group asparagine tert-butyl ester are suspended in 82KG water and 41KG N, N- dimethyl methyl
In amide, iodobenzene diacetate 5.74KG is added, 1.025KG pyridine is added after reaction 15 minutes, the reaction was continued 4 hours.TLC prison
It surveys, after reaction terminates, the extraction of 82KG ethyl acetate, ethyl acetate layer is added in reaction system acidified with citric acid to pH=3-4
It is washed with water once, salt washing is primary, is concentrated under reduced pressure into the half of original volume, and the crystallization of 82KG petroleum ether is added, filters, dries
To final products N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester 3.18KG, white solid, yield 85.0%.Total recovery
71.35%. product map is shown in embodiment 1.
Claims (7)
1. a kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester, it is characterized in that: the following steps are included:
The first step, asparagine are suspended in the mixed liquor of water and acetone, and adjusting pH value with sodium carbonate liquor is alkalinity, are cooled down,
Benzyl chloroformate is added, then temperature reaction after completely reacted, is acidified with hydrochloric acid, and solid is precipitated, intermediate N benzyl is obtained by filtration
Oxygen carbonyl asparagine；
Second step, N- benzyloxycarbonyl group asparagine are suspended in methylene chloride, are passed through isobutene, enriching sulfuric acid, sealing reaction two
It, processing obtains the N- benzyloxycarbonyl group asparagine tert-butyl ester；
Third step, the N- benzyloxycarbonyl group asparagine tert-butyl ester are dissolved in water and n,N-Dimethylformamide, and iodobenzene diacetate is added,
It first reacts and pyridine is added afterwards, the reaction was continued to after terminating, and obtains final products N- benzyloxycarbonyl group -3- the-the third ammonia of amino through processing
Tert-butyl acrylate.
2. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1, feature
Be: for the first step specifically, asparagine is suspended in the mixed liquor of water and acetone, the sodium carbonate with mass fraction 20% is molten
Liquid adjusts pH value between 8-9, cools to 0 DEG C, and benzyl chloroformate is added, is then warming up between 18-20 DEG C and reacts, completely reacted
Later, it is acidified to pH=1 with the hydrochloric acid of 4 equivalents, solid is precipitated, intermediate N benzyloxycarbonyl group asparagine is obtained by filtration.
3. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1 or 2, special
Sign is: the asparagine, water, acetone, and the mass ratio of benzyl chloroformate is 1:10:2 ~ 3:1.5 ~ 1.8.
4. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1, feature
Be: for the second step specifically, N- benzyloxycarbonyl group asparagine is suspended in methylene chloride, T < -5 DEG C of cooling is passed through isobutene,
The concentrated sulfuric acid of mass fraction 98% is added dropwise, seals normal-temperature reaction two days, processing obtains the N- benzyloxycarbonyl group asparagine tert-butyl ester.
5. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1 or 4, special
Sign is: the N- benzyloxycarbonyl group asparagine, methylene chloride, isobutene, the mass ratio of the concentrated sulfuric acid are as follows: 1:(15 ~ 20): (1.5 ~
2): 0.1.
6. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1, feature
Be: the third step is added specifically, the N- benzyloxycarbonyl group asparagine tert-butyl ester is suspended in water and n,N-Dimethylformamide
Pyridine is added after 15 minutes in iodobenzene diacetate, reaction, and the reaction was continued 4 hours, after reaction terminates, reaction system citric acid
Change to pH=3-4, ethyl acetate extraction is added, petroleum ether crystallization obtains final products N- benzyloxycarbonyl group -3- amino-alanine uncle
Butyl ester.
7. a kind of preparation method of N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester according to claim 1 or 6, special
Sign is: the N- benzyloxycarbonyl group asparagine tert-butyl ester, water, n,N-Dimethylformamide, iodobenzene diacetate, pyridine, acetic acid second
Ester, the mass ratio of petroleum ether are as follows: 1:20:10:(1.4 ~ 1.5): 0.25:20:20.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910015050.XA CN109535035A (en) | 2019-01-08 | 2019-01-08 | A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910015050.XA CN109535035A (en) | 2019-01-08 | 2019-01-08 | A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109535035A true CN109535035A (en) | 2019-03-29 |
Family
ID=65834483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910015050.XA Pending CN109535035A (en) | 2019-01-08 | 2019-01-08 | A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109535035A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110218169A (en) * | 2019-06-14 | 2019-09-10 | 重庆医科大学 | Chiral 4-(N- benzyloxycarbonyl group) pyrrolidones synthetic method |
| CN112094204A (en) * | 2019-06-18 | 2020-12-18 | 成都郑源生化科技有限公司 | Method for preparing Fmoc-Tyr (tBu) -OH |
| CN113292432A (en) * | 2021-05-28 | 2021-08-24 | 常州胜杰生命科技股份有限公司 | Preparation application of tert-butyl (7S) -11-methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoate |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4229438A (en) * | 1978-05-12 | 1980-10-21 | Takeda Chemical Industries, Ltd. | Nonapeptides |
| US4271068A (en) * | 1968-05-10 | 1981-06-02 | Ciba-Geigy Corporation | Process for the manufacture of cystine-containing peptides |
| CN1308534A (en) * | 1998-07-06 | 2001-08-15 | 斯克里普斯研究学院 | Angiogenesis inhibitors |
| CN105348147A (en) * | 2015-10-08 | 2016-02-24 | 上海吉尔多肽有限公司 | Synthetic method of Fmoc-Dab(Boc)-OH |
| WO2018182341A1 (en) * | 2017-03-29 | 2018-10-04 | 주식회사 레고켐 바이오사이언스 | Pyrrolobenzodiazepine dimer precursor and ligand-linker conjugate compound thereof |
-
2019
- 2019-01-08 CN CN201910015050.XA patent/CN109535035A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4271068A (en) * | 1968-05-10 | 1981-06-02 | Ciba-Geigy Corporation | Process for the manufacture of cystine-containing peptides |
| US4229438A (en) * | 1978-05-12 | 1980-10-21 | Takeda Chemical Industries, Ltd. | Nonapeptides |
| CN1308534A (en) * | 1998-07-06 | 2001-08-15 | 斯克里普斯研究学院 | Angiogenesis inhibitors |
| CN105348147A (en) * | 2015-10-08 | 2016-02-24 | 上海吉尔多肽有限公司 | Synthetic method of Fmoc-Dab(Boc)-OH |
| WO2018182341A1 (en) * | 2017-03-29 | 2018-10-04 | 주식회사 레고켐 바이오사이언스 | Pyrrolobenzodiazepine dimer precursor and ligand-linker conjugate compound thereof |
Non-Patent Citations (3)
| Title |
|---|
| HANS ULRICH STILZ等: "Discovery of an Orally Active Non-Peptide Fibrinogen Receptor Antagonist Based on the Hydantoin Scaffold", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
| JOSEPH P. KONOPELSKI等: "Dipeptide Surrogates Containing Asparagine-Derived Tetrahydropyrimidinones: Structure and Amide Rotomer Stereochemistry of a Proline Mimic", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| 叶盼盼等: "Hofmann重排反应的应用进展", 《化工生产与技述》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110218169A (en) * | 2019-06-14 | 2019-09-10 | 重庆医科大学 | Chiral 4-(N- benzyloxycarbonyl group) pyrrolidones synthetic method |
| CN110218169B (en) * | 2019-06-14 | 2023-03-28 | 重庆医科大学 | Synthesis method of chiral 4- (N-benzyloxycarbonyl) pyrrolidone |
| CN112094204A (en) * | 2019-06-18 | 2020-12-18 | 成都郑源生化科技有限公司 | Method for preparing Fmoc-Tyr (tBu) -OH |
| CN112094204B (en) * | 2019-06-18 | 2022-06-21 | 成都郑源生化科技有限公司 | Method for preparing Fmoc-Tyr (tBu) -OH |
| CN113292432A (en) * | 2021-05-28 | 2021-08-24 | 常州胜杰生命科技股份有限公司 | Preparation application of tert-butyl (7S) -11-methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109535035A (en) | A kind of preparation method of the N- benzyloxycarbonyl group -3- amino-alanine tert-butyl ester | |
| AU738577B2 (en) | Preparation of cyclohexene carboxylate derivatives | |
| US4606854A (en) | Method of preparing α-L-aspartyl-L-phenylalanine methyl ester and its hydrochloride | |
| EP2186796A1 (en) | Process for producing methionine | |
| CN112358419B (en) | Synthesis process of 3, 4-dichlorophenyl isocyanate | |
| JP3440129B2 (en) | Method for producing glutamine derivative | |
| EP0493812A1 (en) | Process for preparing diketopiperazine derivatives | |
| US4618695A (en) | Method of preparing methyl ester and its hydrochloride | |
| US4345091A (en) | Method of producing N-benzyloxycarbonyl-L-aspartic acid | |
| TASHIRO et al. | Synthesis of 2'-epi-distichonic acid A, an iron-chelating amino acid derivative | |
| CN110903211B (en) | Preparation method of L-theanine | |
| CN106636241B (en) | Method for preparing esmollin intermediate by enzyme method | |
| CN114957087A (en) | Preparation method of intermediate of palovaried | |
| WO2017050092A1 (en) | Method for preparing intermediate for odanacatib | |
| EP3067344A1 (en) | Method for preparing lacosamide | |
| EP0612717B1 (en) | Method for recovering L-phenylalanine | |
| CN109535025B (en) | Preparation method of Evonib intermediate 3, 3-difluorocyclobutylamine hydrochloride | |
| US6008403A (en) | Method for producing optically active amino acid of derivative thereof having high optical purity | |
| JP2951785B2 (en) | Crystallization method of L-phenylalanine | |
| CN116731007B (en) | Preparation method of scopolamine hydrobromide | |
| CN114573470B (en) | Method for synthesizing N-trifluoroacetyl tertiary leucine | |
| CA2236117C (en) | Process for producing optically active cyanohydrins | |
| CN106496012B (en) | A kind of preparation method of Alpha-hydroxy tetradecylic acid | |
| EP0259396B1 (en) | Process for peptide production | |
| CN111217727A (en) | Preparation method of tiopronin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190329 |
|
| WD01 | Invention patent application deemed withdrawn after publication |