CN106083693A - The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester - Google Patents
The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester Download PDFInfo
- Publication number
- CN106083693A CN106083693A CN201610424323.2A CN201610424323A CN106083693A CN 106083693 A CN106083693 A CN 106083693A CN 201610424323 A CN201610424323 A CN 201610424323A CN 106083693 A CN106083693 A CN 106083693A
- Authority
- CN
- China
- Prior art keywords
- phthalyl
- amino
- phenylalanine
- ethyl ester
- ethyl
- 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
- 0 *c1ccc(*)cc1 Chemical compound *c1ccc(*)cc1 0.000 description 6
- GPSFWPXMRZOCLS-UHFFFAOYSA-N CC(C(c1ccccc11)=C=C)C1=C=C Chemical compound CC(C(c1ccccc11)=C=C)C1=C=C GPSFWPXMRZOCLS-UHFFFAOYSA-N 0.000 description 1
- HQXGFBWKSJUMDD-MRVPVSSYSA-N C[C@H](C(c1ccccc11)=C=C)C1=[IH] Chemical compound C[C@H](C(c1ccccc11)=C=C)C1=[IH] HQXGFBWKSJUMDD-MRVPVSSYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
Abstract
The invention provides a kind of N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester; described technique comprises the following steps: (1) amido protecting reacts; (2) esterification; (3) reduction reaction, (4) substitution reaction.The synthesis technique that the present invention provides uses phthalic anhydride protection amino, then through esterification, reduction, replaces and obtain product.The present invention has a low cost, and reaction condition is gentle, and toxicity is low, and technological operation is convenient, and yield is high and the advantage of applicable industrialized production.
Description
Technical field
The present invention relates to the synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, belong to
Field is synthesized in pharmaceutical intermediate.
Background technology
N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, its structural formula is:
N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester is a kind of antineoplastic melphalan
Intermediate, melphalan is a kind of cycle non-specific antitumor drug, due to the specificity of its structure, can enter tumor cell
In and have an effect, cause death of neoplastic cells, thus play antineoplastic action.Clinical proof, melphalan can be used to treat
Multiple myeloma, breast carcinoma, ovarian cancer, chronic lymphocytic and granulocyte type leukemia, malignant lymphoma, multiple bone marrow
Tumor, malignant melanoma, osteosarcoma and soft-tissue tumor etc., its application is quite varied, and Effect value must be affirmed.
There are some intermediate N phthalyl p-(dihydroxy ethyl) amino-L-benzene about this medicine at present
The synthesis technique report of alanine ethyl ester, but the shortcoming such as it is long generally all to there is route, and cost is high, and productivity is low and toxicity is big.
Summary of the invention
It is an object of the invention to provide that a kind of synthetic route is simple, low cost, productivity are high, toxicity is little and can be suitable for industrialization
The synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester produced.
The present invention is to solve existing N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester closes
The shortcoming such as become that synthetic route length present in technique, cost are high, productivity is low and toxicity is big.
The technical scheme is that and the invention provides a kind of N-phthalyl p-(dihydroxy ethyl) amino-L-
The synthesis technique of phenylalanine ethyl ester, uses phthalic anhydride protection amino, uses Alcohol Protection carboxyl, then through reduction, take
In generation, obtain N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester.Synthetic route is as follows:
Concrete synthesis step is as follows:
(1) amido protecting reaction: dissolve raw material to nitro-L-phenylalanine hydrate, Xiang get with solvent and triethylamine
To raw mixture in add phthalic anhydride, be heated to reflux reacting, the reactant liquor obtained is poured in hydrochloric acid solution,
After being sufficiently stirred for, obtain N-phthalyl to nitro-L-phenylalanine；
(2) esterification: with ethanol dissolving step 1 products therefrom, add chlorinating agent in the mixed liquor obtained, heat back
Stream reacts, and obtains N-phthalyl to nitro-L-phenylalanine ethyl ester；
(3) reduction reaction: with solvent dissolving step 2 products therefrom, the mixed liquor obtained is inserted in reactor, to reactor
Middle addition catalyst, is passed through hydrogen reaction under certain condition, obtains N-phthalyl to amino-L-phenylalanine second
Ester；
(4) substitution reaction: with acetic acid and water dissolution step 3 products therefrom, add oxirane in the mixed liquor obtained and enter
Row reaction, then the oxirane of excess in gained reactant liquor is removed, it is added thereto to solvent and extracts, molten with weak base regulation
The pH of liquid is 6～7, then separates organic layer, washes and be dried organic layer, and after removing solvent, available N-phthalyl is p-
(dihydroxy ethyl) amino-L-phenylalanine ethyl ester.
Preferably, the solvent in described step 1 is one or more in chloroform, ethyl acetate, benzene,toluene,xylene
Mixture.
Preferably, the concentration of the hydrochloric acid solution in described step 1 is 0.1 mol/L～2 mol/L.
Preferably, the chlorinating agent in described step 2 is in thionyl chloride, phosphorus oxychloride, Phosphorous chloride., phosphorus pentachloride
Kind.
Preferably, in described step 2, N-phthalyl is 1 to the mol ratio of nitro-L-phenylalanine Yu chlorinating agent:
1.5～1:3, esterification reaction temperature is 50～80 DEG C, and reaction time of esterification is 2～6 hours.
Preferably, the solvent in described step 3 is the mixed of one or more in glacial acetic acid, methanol, ethyl acetate, ethanol
Compound.
Preferably, the one during the catalyst in described step 3 is palladium charcoal, platinum charcoal, Raney's nickel, platinum dioxide.
Preferably, the reduction reaction temperature in described step 3 is 10～40 DEG C, and the reduction reaction time is 5～24 hours；Institute
State in reactor and add after catalyst, first with the air in nitrogen metathesis reactor, then be passed through hydrogen and carry out reduction reaction.
Preferably, the solvent in described step 4 is one or more in dichloromethane, chloroform, ethyl acetate, toluene
Mixture.
Preferably, the weak base in described step 4 is in sodium bicarbonate, sodium carbonate, ammonia, sodium acetate, sodium dihydrogen phosphate
A kind of.
The beneficial effect comprise that: synthesis technique provided by the present invention there is reaction condition gentle, safety
Height, easy and simple to handle, the purification process of product is simple, and purity is high, steady quality, and low in raw material price is easy to get, and it is excellent that total recovery is high etc.
Point, makes totle drilling cost be substantially reduced, and is suitable for the demand of large-scale industrial production.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described.
Embodiment 1
A kind of synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, described technique
Specifically comprise the following steps that
(1) amido protecting reaction:
In there-necked flask, add 120 grams of hydrates to nitro-L-phenylalanine, 500 milliliters of toluene and 100 milliliters
Triethylamine mixes, and stirring is lower adds 85 grams of phthalic anhydrides, is heated to backflow, reacts 3 hours, and reaction is cooled to room after terminating
Temperature, pours in hydrochloric acid solution by the reactant liquor obtained, after being sufficiently stirred for, be filtrated to get 158 grams of N-phthalyls to nitro-
L-phenylalanine solid, the yield of this step is 90%.
(2) esterification:
Take 100 grams of N-phthalyls and nitro-L-phenylalanine and 500 milliliters of ethanol are inserted in there-necked flask mixed
Closing, while stirring 80 grams of thionyl chlorides of dropping, after dropping, be heated to backflow, react 3 hours, reaction is cooled to after terminating
Room temperature, in reactant liquor add petroleum ether 100 grams, after being sufficiently stirred for, be filtrated to get 100 grams of N-phthalyls to nitro-
L-phenylalanine ethyl ester solid, the yield of this step is 93%.
(3) reduction reaction:
Take 100 grams of N-phthalyls nitro-L-phenylalanine ethyl ester and 800 milliliters of ethanol are inserted in there-necked flask
Mixing, adds 3 grams of palladium charcoals and 50 grams of water, with the air in nitrogen metathesis reactor twice, then with in hydrogen exchange reactor
Nitrogen twice, is passed through hydrogen under stirring and reacts, and judges reaction end through thin layer chromatography (TLC), after reaction terminates, filters
Removing palladium charcoal, decompression boils off solvent, obtains 91 grams of N-phthalyls to amino-L-phenylalanine ethyl ester solid, this step
Yield be 99%.
(4) substitution reaction:
Taking 91 grams of N-phthalyls to amino-L-phenylalanine ethyl ester solid and 600 milliliters of mass fractions is 50%
Aqueous acetic acid insert in there-necked flask and mix, the lower oxirane that adds of stirring reacts, and sentences through thin layer chromatography (TLC)
Disconnected reaction end, after reaction terminates, adds the oxirane of heat extraction excess, adds ethyl acetate, slowly add under stirring after cooling
The pH entering manganese hydrogen sodium regulating solution is 6～7, after separating organic layer, then is extracted with ethyl acetate twice, merges organic layer, water
Washing and be dried organic layer, decompression boils off solvent and obtains 110 grams of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylpropyl alcohol ammonia
Acetoacetic ester, the yield of this step is 96%.
The total recovery of the most whole synthesis technique is 79.5%.
Embodiment 2
The synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, described technique includes
Following steps:
(1) amido protecting reaction: dissolve the raw material hydrate to nitro-L-phenylalanine, Xiang get with solvent and triethylamine
To raw mixture in add phthalic anhydride, be heated to reflux reacting, the reactant liquor obtained is poured in hydrochloric acid solution,
After being sufficiently stirred for, obtain N-phthalyl to nitro-L-phenylalanine；
(2) esterification: with ethanol dissolving step 1 products therefrom, add chlorinating agent in the mixed liquor obtained, heat back
Stream reacts, and obtains N-phthalyl to nitro-L-phenylalanine ethyl ester；
(3) reduction reaction: with solvent dissolving step 2 products therefrom, the mixed liquor obtained is inserted in reactor, to reactor
Middle addition catalyst, is passed through hydrogen reaction under certain condition, obtains N-phthalyl to amino-L-phenylalanine second
Ester；
(4) substitution reaction: with acetic acid and water dissolution step 3 products therefrom, add oxirane in the mixed liquor obtained and enter
Row reaction, then the oxirane of excess in gained reactant liquor is removed, it is added thereto to solvent and extracts, molten with weak base regulation
The pH of liquid is 6～7, then separates organic layer, washes and be dried organic layer, and after removing solvent, available N-phthalyl is p-
(dihydroxy ethyl) amino-L-phenylalanine ethyl ester.
Solvent in described step 1 is the mixing of one or more in chloroform, ethyl acetate, benzene,toluene,xylene
Thing.
The concentration of the hydrochloric acid solution in described step 1 is 0.1mol/L～2mol/L.
Chlorinating agent in described step 2 is the one in thionyl chloride, phosphorus oxychloride, Phosphorous chloride., phosphorus pentachloride.
In described step 2, N-phthalyl is 1:1.5～1 to the mol ratio of nitro-L-phenylalanine Yu chlorinating agent:
3, esterification reaction temperature is 50～80 DEG C, and reaction time of esterification is 2～6 hours.
Solvent in described step 3 is the mixture of one or more in glacial acetic acid, methanol, ethyl acetate, ethanol.
Catalyst in described step 3 is the one in palladium charcoal, platinum charcoal, Raney's nickel, platinum dioxide.
Reduction reaction temperature in described step 3 is 10～40 DEG C, and the reduction reaction time is 5～24 hours；Described reaction
Device adds after catalyst, first with the air in nitrogen metathesis reactor, then is passed through hydrogen and carries out reduction reaction.
Solvent in described step 4 is the mixture of one or more in dichloromethane, chloroform, ethyl acetate, toluene.
Weak base in described step 4 is the one in sodium bicarbonate, sodium carbonate, ammonia, sodium acetate, sodium dihydrogen phosphate.
Embodiment 3
The synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, described technique includes
Following steps:
(1) amido protecting reaction: dissolve the raw material hydrate to nitro-L-phenylalanine, Xiang get with solvent and triethylamine
To raw mixture in add phthalic anhydride, be heated to reflux reacting, the reactant liquor obtained is poured in hydrochloric acid solution,
After being sufficiently stirred for, obtain N-phthalyl to nitro-L-phenylalanine；
(2) esterification: with ethanol dissolving step 1 products therefrom, add chlorinating agent in the mixed liquor obtained, heat back
Stream reacts, and obtains N-phthalyl to nitro-L-phenylalanine ethyl ester；
(3) reduction reaction: with solvent dissolving step 2 products therefrom, the mixed liquor obtained is inserted in reactor, to reactor
Middle addition catalyst, is passed through hydrogen reaction under certain condition, obtains N-phthalyl to amino-L-phenylalanine second
Ester；
(4) substitution reaction: with acetic acid and water dissolution step 3 products therefrom, add oxirane in the mixed liquor obtained and enter
Row reaction, then the oxirane of excess in gained reactant liquor is removed, it is added thereto to solvent and extracts, molten with weak base regulation
The pH of liquid is 6～7, then separates organic layer, washes and be dried organic layer, and after removing solvent, available N-phthalyl is p-
(dihydroxy ethyl) amino-L-phenylalanine ethyl ester.
Solvent in described step 1 is the mixing of one or more in chloroform, ethyl acetate, benzene,toluene,xylene
Thing.
Chlorinating agent in described step 2 is the one in thionyl chloride, phosphorus oxychloride, Phosphorous chloride., phosphorus pentachloride.
Solvent in described step 3 is the mixture of one or more in glacial acetic acid, methanol, ethyl acetate, ethanol.
Catalyst in described step 3 is the one in palladium charcoal, platinum charcoal, Raney's nickel, platinum dioxide.
Solvent in described step 4 is the mixture of one or more in dichloromethane, chloroform, ethyl acetate, toluene.
Weak base in described step 4 is the one in sodium bicarbonate, sodium carbonate, ammonia, sodium acetate, sodium dihydrogen phosphate.
Embodiment 4
The synthesis technique of N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, described technique includes
Following steps:
(1) amido protecting reaction: dissolve the raw material hydrate to nitro-L-phenylalanine, Xiang get with solvent and triethylamine
To raw mixture in add phthalic anhydride, be heated to reflux reacting, the reactant liquor obtained is poured in hydrochloric acid solution,
After being sufficiently stirred for, obtain N-phthalyl to nitro-L-phenylalanine；
(2) esterification: with ethanol dissolving step 1 products therefrom, add chlorinating agent in the mixed liquor obtained, heat back
Stream reacts, and obtains N-phthalyl to nitro-L-phenylalanine ethyl ester；
(3) reduction reaction: with solvent dissolving step 2 products therefrom, the mixed liquor obtained is inserted in reactor, to reactor
Middle addition catalyst, is passed through hydrogen reaction under certain condition, obtains N-phthalyl to amino-L-phenylalanine second
Ester；
(4) substitution reaction: with acetic acid and water dissolution step 3 products therefrom, add oxirane in the mixed liquor obtained and enter
Row reaction, then the oxirane of excess in gained reactant liquor is removed, it is added thereto to solvent and extracts, molten with weak base regulation
The pH of liquid is 6～7, then separates organic layer, washes and be dried organic layer, and after removing solvent, available N-phthalyl is p-
(dihydroxy ethyl) amino-L-phenylalanine ethyl ester.
Embodiment 5
On the basis of embodiment 4, the present invention can also include one of following, or the most any one technical scheme or
The a plurality of Welded joint of person:
Solvent in described step 1 is the mixing of one or more in chloroform, ethyl acetate, benzene,toluene,xylene
Thing.
The concentration of the hydrochloric acid solution in described step 1 is 0.1mol/L～2mol/L.
Chlorinating agent in described step 2 is the one in thionyl chloride, phosphorus oxychloride, Phosphorous chloride., phosphorus pentachloride.
In described step 2, N-phthalyl is 1:1.5～1 to the mol ratio of nitro-L-phenylalanine Yu chlorinating agent:
3, esterification reaction temperature is 50～80 DEG C, and reaction time of esterification is 2～6 hours.
Solvent in described step 3 is the mixture of one or more in glacial acetic acid, methanol, ethyl acetate, ethanol.
Catalyst in described step 3 is the one in palladium charcoal, platinum charcoal, Raney's nickel, platinum dioxide.
Reduction reaction temperature in described step 3 is 10～40 DEG C, and the reduction reaction time is 5～24 hours；Described reaction
Device adds after catalyst, first with the air in nitrogen metathesis reactor, then is passed through hydrogen and carries out reduction reaction.
Solvent in described step 4 is the mixture of one or more in dichloromethane, chloroform, ethyl acetate, toluene.
Weak base in described step 4 is the one in sodium bicarbonate, sodium carbonate, ammonia, sodium acetate, sodium dihydrogen phosphate.
Claims (10)
- The synthesis technique of 1.N-phthalyl p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester, it is characterised in that described Technique comprises the following steps:(1) amido protecting reaction: dissolve the raw material hydrate to nitro-L-phenylalanine, to obtain with solvent and triethylamine Adding phthalic anhydride in raw mixture, be heated to reflux reacting, the reactant liquor obtained is poured in hydrochloric acid solution, fully After stirring, obtain N-phthalyl to nitro-L-phenylalanine；(2) esterification: with ethanol dissolving step 1 products therefrom, adds chlorinating agent in the mixed liquor obtained, be heated to reflux into Row reaction, obtains N-phthalyl to nitro-L-phenylalanine ethyl ester；(3) reduction reaction: with solvent dissolving step 2 products therefrom, the mixed liquor obtained is inserted in reactor, added in reactor Enter catalyst, be passed through hydrogen reaction under certain condition, obtain N-phthalyl to amino-L-phenylalanine ethyl ester；(4) substitution reaction: with acetic acid and water dissolution step 3 products therefrom, add oxirane in the mixed liquor obtained and carry out instead Should, then the oxirane of excess in gained reactant liquor is removed, it is added thereto to solvent and extracts, with weak base regulation solution PH is 6～7, then separates organic layer, washes and be dried organic layer, the available p-(dihydroxy of N-phthalyl after removing solvent Ethyl) amino-L-phenylalanine ethyl ester.
- 2. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the solvent in described step 1 is the one in chloroform, ethyl acetate, benzene,toluene,xylene or several The mixture planted.
- 3. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the concentration of the hydrochloric acid solution in described step 1 is 0.1mol/L～2mol/L.
- 4. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the chlorinating agent in described step 2 is in thionyl chloride, phosphorus oxychloride, Phosphorous chloride., phosphorus pentachloride A kind of.
- 5. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that in described step 2, the mol ratio of nitro-L-phenylalanine with chlorinating agent is by N-phthalyl 1:1.5～1:3, esterification reaction temperature is 50～80 DEG C, and reaction time of esterification is 2～6 hours.
- 6. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the solvent in described step 3 is one or more in glacial acetic acid, methanol, ethyl acetate, ethanol Mixture.
- 7. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the catalyst in described step 3 is the one in palladium charcoal, platinum charcoal, Raney's nickel, platinum dioxide.
- 8. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the reduction reaction temperature in described step 3 is 10～40 DEG C, and the reduction reaction time is 5～24 hours； Described reactor adds after catalyst, first with the air in nitrogen metathesis reactor, then is passed through hydrogen and carries out reduction reaction.
- 9. according to the conjunction of the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Become technique, it is characterised in that the solvent in described step 4 is one or more in dichloromethane, chloroform, ethyl acetate, toluene Mixture.
- 10. according to the N-phthalyl described in claim 1 p-(dihydroxy ethyl) amino-L-phenylalanine ethyl ester Synthesis technique is characterized in that the weak base in described step 4 is in sodium bicarbonate, sodium carbonate, ammonia, sodium acetate, sodium dihydrogen phosphate One.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610424323.2A CN106083693A (en) | 2016-06-14 | 2016-06-14 | The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610424323.2A CN106083693A (en) | 2016-06-14 | 2016-06-14 | The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106083693A true CN106083693A (en) | 2016-11-09 |
Family
ID=57846600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610424323.2A Pending CN106083693A (en) | 2016-06-14 | 2016-06-14 | The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106083693A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041214A (en) * | 2019-05-06 | 2019-07-23 | 凯瑞斯德生化(苏州)有限公司 | A kind of Melphalan intermediate and preparation method thereof |
| CN114315618A (en) * | 2021-12-04 | 2022-04-12 | 浙江恒腾福生物科技集团有限公司 | Preparation method of synthetic melphalan |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0233733A2 (en) * | 1986-02-19 | 1987-08-26 | Kureha Kagaku Kogyo Kabushiki Kaisha | Process for producing N-phthaloyl-p-nitro-L-phenylalanine |
-
2016
- 2016-06-14 CN CN201610424323.2A patent/CN106083693A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0233733A2 (en) * | 1986-02-19 | 1987-08-26 | Kureha Kagaku Kogyo Kabushiki Kaisha | Process for producing N-phthaloyl-p-nitro-L-phenylalanine |
Non-Patent Citations (1)
| Title |
|---|
| BYOUNG-HYOUN KIM,等: "Chiral Recognition of N-Phthaloyl,N-Tetrachlorophthaloyl,and N-Naphthaloyl a-Amino Acids and Their Esters on Polysaccharide-Derived Chiral Stationary Phases", 《CHIRALITY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041214A (en) * | 2019-05-06 | 2019-07-23 | 凯瑞斯德生化(苏州)有限公司 | A kind of Melphalan intermediate and preparation method thereof |
| CN114315618A (en) * | 2021-12-04 | 2022-04-12 | 浙江恒腾福生物科技集团有限公司 | Preparation method of synthetic melphalan |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102584795B (en) | Preparing method of crizotinib | |
| CN102070421A (en) | Method for synthesizing veratraldehyde | |
| CN106083693A (en) | The N phthalyl synthesis technique to (dihydroxy ethyl) amino L phenylalanine ethyl ester | |
| CN113416150B (en) | Synthetic method of lobaplatin intermediate | |
| CN101654419A (en) | Preparation method of fluvoxamine maleate | |
| CN102952169A (en) | Synthetic method of 6-methyl-17alpha-acetoxyl-19-norpregna-4,6-dialkyl-3,20-diketone | |
| CN101747278A (en) | Method for synthesizing 1-chloroformyl-3-methyl sulfonyl-2-imidazo flavanone | |
| CN105017365A (en) | Method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone | |
| CN104788353B (en) | A kind of method for synthesizing 4 oxo L proline derivatives | |
| CN108707111A (en) | A kind of green synthesis method of 6 (5H)-phenanthridines ketone derivatives | |
| CN105272911B (en) | A kind of preparation method of Sorafenib Tosylate | |
| CN108558758A (en) | A kind of synthetic method of 4- fluorine isoquinolin -5- amine | |
| CN109422685A (en) | A kind of synthetic method of N- acetyl group phenanthridines -6- amide and its derivative | |
| CN103833821A (en) | Synthesis method for 3-succinic acid-30-stearyl glycyrrhetinic acid ester | |
| CN107141257A (en) | A kind of naphthalimide polyamines conjugate containing terminal substituent and its preparation method and application | |
| CN105924390A (en) | Synthesis method of metafenib | |
| CN104230781A (en) | Method for synthesizing halogenated 3-methyl indole compound | |
| CN109824553A (en) | 2-((tert-butoxycarbonyl) amino) ethyl-1- sulfonic acid and preparation method thereof | |
| CN106543040B (en) | A kind of synthetic method of medicine intermediate carbamate compounds | |
| CN110015960A (en) | The preparation method and application of 1,3- bis- (4,4- methyl formate phenyl) acetone | |
| CN110903240A (en) | Preparation method of broad-spectrum anticancer drug cabozantinib | |
| CN104387435B (en) | Compound and preparation method and application thereof | |
| CN103524502A (en) | Preparation method of tadalafil | |
| CN101935317A (en) | Synthesizing method of 2-methyl-7-(substituted pyrimidine-4-amino)-4-(substituted piperazine-1-base) piperidine-1-base) isoindoline-1-ketone and intermediate thereof | |
| CN107304171A (en) | A kind of synthetic method of Oseltamivir |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20161109 |