CN113045469A - Synthesis method of lactam compound - Google Patents
Synthesis method of lactam compound Download PDFInfo
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- CN113045469A CN113045469A CN202110307491.4A CN202110307491A CN113045469A CN 113045469 A CN113045469 A CN 113045469A CN 202110307491 A CN202110307491 A CN 202110307491A CN 113045469 A CN113045469 A CN 113045469A
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- -1 lactam compound Chemical class 0.000 title claims abstract description 22
- 238000001308 synthesis method Methods 0.000 title abstract description 14
- 239000000047 product Substances 0.000 claims abstract description 56
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000012043 crude product Substances 0.000 claims abstract description 18
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 17
- CJYQZTZSYREQBD-UHFFFAOYSA-N n-fluorobenzenesulfonamide Chemical compound FNS(=O)(=O)C1=CC=CC=C1 CJYQZTZSYREQBD-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 16
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 16
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 150000003951 lactams Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 229910000510 noble metal Inorganic materials 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 238000007154 radical cyclization reaction Methods 0.000 abstract description 2
- 150000003254 radicals Chemical class 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000007363 ring formation reaction Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 150000003953 γ-lactams Chemical group 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a method for synthesizing lactam compound, (1) under the protection of gas, dissolving N-F benzene sulfonamide and acyl chloride in an organic solvent, uniformly stirring, and reacting to obtain a crude product; (2) recrystallizing the crude product to obtain a product A; (3) dissolving the product A obtained in the step (2), cuprous iodide and phenanthroline in a mixed organic solvent, and heating for reaction to obtain an intermediate; (4) and dissolving the intermediate, adding tetrabutylammonium fluoride, and stirring to obtain the target product. The invention selects the commercially available N-F benzene sulfonamide and acyl chloride as the starting raw materials, and the materials are easy to obtain; the synthesis method of the invention selects the commercial cheap and easily available cuprous iodide as the catalyst, avoids using expensive noble metal catalyst, and effectively improves the economy; the whole synthesis method has mild reaction conditions; the target compound is obtained through free radical cyclization, the use of other oxidants or noble metal catalysts is avoided, and the synthesis cost is low.
Description
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a synthesis method of a five-membered or six-membered ring lactam compound.
Background
In heterocyclic compounds, the lactam structure is an extremely important moiety, widely present in various natural products as well as in pharmaceutical molecules. Some lactam compounds have good biological activity and have been verified to have antibacterial, antiviral, and anti-senile dementia effects. For example, HIV-1 protease inhibitors containing a gamma-lactam structure have good water solubility and pharmacological activity. Valerolactam has also received much attention from chemists as an important organic synthesis intermediate. Inhibitors containing valerolactam structures have been reported to exhibit good activity. Therefore, it is of interest to find an efficient scheme for the synthesis of five-or six-membered ring lactam compounds.
At present, various methods for synthesizing five-or six-membered lactam compounds have been reported in the literature. Examples of the cyclization include a diffusion cyclization, a 4+1 cyclization, and a transition metal-catalyzed cyclization. However, these schemes have certain disadvantages, such as that the method for synthesizing gamma-lactam by beta-lactam cyclization is limited to specific substrate types, and needs stronger alkali (LDA and the like), which causes great inconvenience and pollution; 4+1 cyclization or other cyclization processes require the use of relatively expensive catalysts or require relatively high temperatures; transition metal catalyzed lactam compounds are usually catalyzed by the noble metals rhodium (Rh), iridium (Ir), palladium (Pd), gold (Au), etc., and generally carried out at 50 to 70 ℃. Although the scheme realizes the preparation of a series of five-membered or six-membered ring lactam compounds, the preparation methods have certain limitations or need to use expensive catalysts.
Disclosure of Invention
The invention aims to provide a simple lactam synthesis method aiming at the disadvantages of the existing synthesis method; the synthesis method is simple and convenient and has low cost.
The invention is realized by the following technical scheme:
a method for synthesizing lactam compound comprises the following steps:
(1) under the protection of gas, dissolving N-F benzene sulfonamide and acyl chloride in an organic solvent, uniformly stirring, and reacting to obtain a crude product;
(2) recrystallizing the crude product to obtain a product A; product a was a white solid;
(3) dissolving the product A obtained in the step (2), cuprous iodide (CuI) and phenanthroline in a mixed organic solvent, and heating for reaction to obtain an intermediate;
(4) dissolving the intermediate, adding tetrabutylammonium fluoride (TBAF), and stirring to obtain a target product.
Further, in the step (1), under the protection of nitrogen, the N-F benzene sulfonamide and acyl chloride are dissolved in Dichloromethane (DCM) and stirred uniformly, and the mixture reacts for 2.5 hours at room temperature to obtain a crude product. The crude product is the crude product of the product A.
Further, the molar ratio of the N-F benzenesulfonamide to the acid chloride is 1: (1-1.5).
Further, the structural formula of the acyl chloride is shown in the specification
When the acid chloride is
When the reaction is carried out, the product A obtained is
When the acid chloride is
When the reaction is carried out, the product A is obtained
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
Further, the molar ratio of the cuprous iodide, the phenanthroline and the product A in the step (3) is (0.5-1): (1-1.5): 10; the heating temperature is 60-80 ℃, and the reaction time is 1.5 hours; the mixed organic solvent is a mixture of Dichloroethane (DCE) and methanol (MeOH).
Further, when the product A is
When the intermediate obtained in the step (3) is
When the product A is
When the intermediate obtained in the step (3) is
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
Further, the volume ratio of the dichloroethane to the methanol is 10: 1.
further, in the step (4), the intermediate is dissolved in Tetrahydrofuran (THF) and tetrabutylammonium fluoride (TBAF) is added, and the reaction is stirred at room temperature for 16 hours to obtain the target product.
Further, the molar ratio of the intermediate to the tetrahydrofuran is 1: (1-1.5).
Further, when the intermediate is
Then, the target product obtained by the reaction in the step (4) is the five-membered ring lactam
When the intermediate is
Then, the target product obtained by the reaction in the step (4) is the six-membered cyclic lactam
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
Specifically, the synthetic route of the invention is as follows:
(1) when the acid chloride is
By the scheme of the inventionSynthesizing five-membered cyclic lactam, wherein the synthetic route is shown as (a) and (b): wherein R represents aryl, R1、R2、R3Represents an alkyl group;
(2) when the acid chloride is
By the scheme of the invention, the six-membered cyclic lactam can be synthesized, and the synthetic routes are shown as (c) and (d): wherein R represents aryl, R1、R2、R3Represents an alkyl group;
the invention has the beneficial effects that:
the invention selects the commercially available N-F benzene sulfonamide and acyl chloride as the starting raw materials, and the materials are easy to obtain; meanwhile, the synthesis method of the invention selects the commercial cheap and easily available cuprous iodide as the catalyst, thereby avoiding the use of expensive noble metal catalyst and effectively improving the economy; the whole synthesis method has mild reaction conditions; the target compound is obtained through free radical cyclization, the use of other oxidants or noble metal catalysts is avoided, and the synthesis cost is low.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A method for synthesizing lactam compound comprises the following steps: the acyl chloride selected in the synthesis method is
Wherein R is aryl, R1Is methyl, i.e.
(1) Under the protection of nitrogen, N-F benzene sulfonamide,
(acyl chloride) is dissolved in dichloromethane and stirred evenly, and stirred and reacted for 2.5 hours at room temperature to obtain
(this is the crude product of product A); in this reaction step N-F benzenesulfonamide with
The molar ratio is 1: 1.2;
(2) recrystallizing the crude product of the product A obtained in the step (1) to obtain the product A
(product A);
(3) dissolving the product A obtained in the step (2), cuprous iodide and phenanthroline in a mixed solvent of dichloroethane and methanol, and heating and reacting at 70 ℃ for 1.5 hours to obtain the copper iodide copper phenanthroline
(4) subjecting the product obtained in step (3)
Dissolving the intermediate in tetrahydrofuran, adding tetrabutylammonium fluoride (TBAF), stirring at room temperature for reaction for 16 hours to obtain the target product, namely the five-membered cyclic lactam
The molar ratio of the intermediate to tetrahydrofuran in this step is 1: 1.2.
the synthetic route of this example 1 is specifically shown in the following equations (1) and (2):
example 2
A method for synthesizing lactam compound comprises the following steps: the acyl chloride selected in the synthesis method is
Wherein R is aryl, R2、R3Is methyl, i.e.
(1) Under the protection of nitrogen, N-F benzene sulfonamide,
(acyl chloride) is dissolved in dichloromethane and stirred evenly, and stirred and reacted for 2.5 hours at room temperature to obtain
(i.e., crude product a); in this reaction step N-F benzenesulfonamide with
The molar ratio is 1: 1.2;
(2) recrystallizing the crude product of the product A obtained in the step (1) to obtain the product A
(product A);
(3) dissolving the product A obtained in the step (2), cuprous iodide and phenanthroline in a mixed solvent of dichloroethane and methanol, and heating and reacting at 70 ℃ for 1.5 hours to obtain the copper iodide copper phenanthroline
(5) subjecting the product obtained in step (3)
Dissolving the intermediate in tetrahydrofuran, adding tetrabutylammonium fluoride (TBAF), stirring at room temperature for reaction for 16 hours to obtain the target product, namely the hexatomic cyclic lactam
And the molar ratio of the intermediate to tetrahydrofuran is 1: 1.2.
the synthetic route of this example 2 is specifically shown in the following equations (1) and (2):
example 3
A method for synthesizing lactam compound comprises the following steps: the acyl chloride selected in the synthesis method is
Wherein R is aryl, R1Is methyl, i.e.
(1) Under the protection of nitrogen, N-F benzene sulfonamide,
(acyl chloride) is dissolved in dichloromethane and stirred evenly, and stirred and reacted for 2.5 hours at room temperature to obtain
(i.e., crude product a); wherein N-F benzenesulfonamide and
the molar ratio is 1: 1;
(2) recrystallizing the crude product of the product A obtained in the step (1) to obtain the product A
(product A);
(3) dissolving the product A obtained in the step (2), cuprous iodide and phenanthroline in a mixed solvent of dichloroethane and methanol, and heating and reacting at 80 ℃ for 1.5 hours to obtain the copper iodide copper phenanthroline
(6) subjecting the product obtained in step (3)
Dissolving the intermediate in tetrahydrofuran, adding tetrabutylammonium fluoride (TBAF), stirring at room temperature for reaction for 16 hours to obtain the target product, namely the five-membered cyclic lactam
And the molar ratio of the intermediate to tetrahydrofuran is 1: 1.5.
example 4
A method for synthesizing lactam compound comprises the following steps: the acyl chloride selected in the synthesis method is
Wherein R is aryl, R1Is methyl, i.e.
(1) Under the protection of nitrogen, N-F benzene sulfonamide,
(acyl chloride) is dissolved in dichloromethane and stirred evenly, and stirred and reacted for 2.5 hours at room temperature to obtain
(i.e., crude product a); wherein N-F benzenesulfonamide and
the molar ratio is 1: 1.5;
(2) recrystallizing the crude product of the product A obtained in the step (1) to obtain the product A
(product A);
(3) dissolving the product A obtained in the step (2), cuprous iodide and phenanthroline in a mixed solvent of dichloroethane and methanol, and heating and reacting at 60 ℃ for 1.5 hours to obtain the copper iodide copper phenanthroline
(4) subjecting the product obtained in step (3)
Dissolving the intermediate in tetrahydrofuran, adding tetrabutylammonium fluoride (TBAF), stirring at room temperature for reaction for 16 hours to obtain the target product, namely the five-membered cyclic lactam
And the molar ratio of the intermediate to tetrahydrofuran is 1: 1.
the difference between the above example 1 and example 2 is that the acyl chloride is selected differently, and the rest of the synthesis conditions are the same; examples 3 and 4 are the same as those of example 1 except for the addition ratio of each component and the difference in reaction conditions.
The above-mentioned preferred embodiments of the present invention are provided for illustration only and not for the purpose of limiting the invention. Obvious variations or modifications of the present invention are within the scope of the present invention.
Claims (10)
1. A method for synthesizing a lactam compound, comprising the steps of:
(1) under the protection of gas, dissolving N-F benzene sulfonamide and acyl chloride in an organic solvent, uniformly stirring, and reacting to obtain a crude product;
(2) recrystallizing the crude product to obtain a product A;
(3) dissolving the product A, cuprous iodide and phenanthroline obtained in the step (2) in a mixed organic solvent, and heating for reaction to obtain an intermediate;
(4) and dissolving the intermediate, adding tetrabutylammonium fluoride, and stirring to obtain the target product.
2. The method for synthesizing lactam compound as claimed in claim 1, wherein in step (1), under nitrogen protection, N-F benzene sulfonamide and acyl chloride are dissolved in dichloromethane and stirred uniformly, and reacted at room temperature for 2.5 hours to obtain crude product.
3. The method of claim 2, wherein the molar ratio of N-F benzenesulfonamide to acid chloride is 1: (1-1.5).
4. The method of claim 3, wherein the acid chloride has the formula
When the acid chloride is
When the reaction is carried out, the product A obtained is
When the acid chloride is
When the reaction is carried out, the product A is obtained
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
5. The method according to claim 4, wherein the molar ratio of the cuprous iodide, the phenanthroline and the product A in step (3) is (0.5-1): (1-1.5): 10; the heating temperature is 60-80 ℃, and the reaction time is 1.5 hours; the mixed organic solvent is a mixture of dichloroethane and methanol.
6. The method of claim 5, wherein when said product A is selected from the group consisting of
When the intermediate obtained in the step (3) is
When the product A is
When the intermediate obtained in the step (3) is
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
7. The method of claim 5, wherein the volume ratio of dichloroethane to methanol is 10: 1.
8. the method according to claim 6, wherein the intermediate in step (4) is dissolved in tetrahydrofuran, tetrabutylammonium fluoride is added, and the reaction is stirred at room temperature for 16 hours to obtain the target product.
9. The method of claim 8, wherein the molar ratio of the intermediate to the tetrahydrofuran is 1: (1-1.5).
10. The method of claim 9, wherein the intermediate is a lactam compound
Then, the target product obtained by the reaction in the step (4) is the five-membered ring lactam
When the intermediate is
Then, the target product obtained by the reaction in the step (4) is the six-membered cyclic lactam
Wherein R represents aryl, R1、R2、R3Represents an alkyl group.
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| CN202110307491.4A CN113045469A (en) | 2021-03-23 | 2021-03-23 | Synthesis method of lactam compound |
| PCT/CN2021/135945 WO2022199124A1 (en) | 2021-03-23 | 2021-12-07 | Method for synthesizing lactam compound |
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| US7166624B2 (en) * | 2002-12-18 | 2007-01-23 | Smithkline Beecham Corporation | Peptide deformylase inhibitors |
| JP4905772B2 (en) * | 2006-06-06 | 2012-03-28 | 富士フイルム株式会社 | Resin, positive resist composition containing the resin, protective film forming composition containing the resin, pattern forming method using the positive resist composition, and turn forming method using the protective film forming composition |
| CN113045469A (en) * | 2021-03-23 | 2021-06-29 | 上海沃凯生物技术有限公司 | Synthesis method of lactam compound |
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- 2021-12-07 WO PCT/CN2021/135945 patent/WO2022199124A1/en active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| IRIS ANNE SCHULTE-WÜLWER，ET AL.: "Copper(I)-Catalyzed Intramolecular Addition of N-Chloroamides to Double Bonds; an Efficient Synthesis of Lactams from Unsaturated Amides", 《SYNTHESIS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022199124A1 (en) * | 2021-03-23 | 2022-09-29 | 上海沃凯生物技术有限公司 | Method for synthesizing lactam compound |
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