CN113185521A - Method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compound by cyclopropyl ring opening - Google Patents
Method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compound by cyclopropyl ring opening Download PDFInfo
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- CN113185521A CN113185521A CN202110501673.5A CN202110501673A CN113185521A CN 113185521 A CN113185521 A CN 113185521A CN 202110501673 A CN202110501673 A CN 202110501673A CN 113185521 A CN113185521 A CN 113185521A
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- 238000007142 ring opening reaction Methods 0.000 title claims abstract description 20
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000001408 amides Chemical class 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 238000000746 purification Methods 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract 2
- -1 tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds Chemical class 0.000 claims description 13
- 239000000047 product Substances 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 238000002390 rotary evaporation Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000003446 ligand Substances 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 description 17
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 9
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- SKUULLWVNNWVFM-UHFFFAOYSA-N 6-(3-chlorophenyl)-1h-1,3,5-triazin-2-one Chemical compound ClC1=CC=CC(C=2NC(=O)N=CN=2)=C1 SKUULLWVNNWVFM-UHFFFAOYSA-N 0.000 description 2
- WVHFYUPPAZHEOX-UHFFFAOYSA-N 6-(4-bromophenyl)-1h-1,3,5-triazin-2-one Chemical compound C1=CC(Br)=CC=C1C1=NC=NC(=O)N1 WVHFYUPPAZHEOX-UHFFFAOYSA-N 0.000 description 2
- HEVGASYHOZQJLI-UHFFFAOYSA-N 6-(4-chlorophenyl)-1h-1,3,5-triazin-2-one Chemical compound C1=CC(Cl)=CC=C1C1=NC=NC(=O)N1 HEVGASYHOZQJLI-UHFFFAOYSA-N 0.000 description 2
- FSFOXKHVEFQBKV-UHFFFAOYSA-N 6-(4-fluorophenyl)-1h-1,3,5-triazin-2-one Chemical compound C1=CC(F)=CC=C1C1=NC=NC(=O)N1 FSFOXKHVEFQBKV-UHFFFAOYSA-N 0.000 description 2
- NJCDRURWJZAMBM-UHFFFAOYSA-N 6-phenyl-1h-1,3,5-triazin-2-one Chemical class OC1=NC=NC(C=2C=CC=CC=2)=N1 NJCDRURWJZAMBM-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
- ZZWOMYLGLDATRS-UHFFFAOYSA-N 6-(3-methylphenyl)-1h-1,3,5-triazin-2-one Chemical compound CC1=CC=CC(C=2NC(=O)N=CN=2)=C1 ZZWOMYLGLDATRS-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- HUDWXDLBWRHCKO-UHFFFAOYSA-N n'-phenylpyridine-4-carbohydrazide Chemical compound C=1C=NC=CC=1C(=O)NNC1=CC=CC=C1 HUDWXDLBWRHCKO-UHFFFAOYSA-N 0.000 description 1
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a method for preparing a tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compound by ring opening of cyclopropyl, and a method for preparing the tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compound by ring opening of cyclopropyl, wherein amide, an organic solvent and oxalyl chloride are added into a reaction vessel, the reaction is carried out for 0.5 to 2 hours at the reaction temperature of 40 to 80 ℃, then, cyclopropanecarboxamidine hydrochloride is added into the reaction vessel, the temperature is increased to ensure that the temperature in the reaction vessel reaches 110-130 ℃, the reaction is carried out for 6 to 24 hours at the temperature, and a target product is obtained by separation and purification after the reaction is finished. Compared with the prior similar reaction, the reaction does not need to add a metal catalyst and a ligand except for necessary solvent and reaction bottom, and is promoted to be efficiently carried out by utilizing hydrochloric acid brought by the cyprocoamidine hydrochloride, and meanwhile, the reaction condition of the reaction is mild, green, environment-friendly and safe. In general, the reaction is environment-friendly, the operation is simple and easy, the product yield is high, and the product has potential medicinal value.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compounds by cyclopropyl ring opening.
Background
Cyclopropane, because of its large ring tension, can be ring-opened with the aid of the release of strain energy (27.5kcal/mol), and is therefore often referred to as C3Building blocks are used for synthesizing other condensed rings, such as cyclopropane substituted by electron-donating and electron-withdrawing groups, which can be easily captured by different double bonds (such as C ═ C, C ═ N and C ═ O) so as to carry out ring expansion to synthesize various condensed ring compounds. Fused heterocycles with ring-bound nitrogen are present in many approved drugs and clinical candidates, such as: anegliptin, RSV fusion inhibitors, Syk inhibitors, HCV inhibitors, divalpron, faxipulon, larotinib, oxiprone, ponatinib, and the like. The tetrahydropyrrolo [1,2-a ] thus synthesized]1,3, 5-triazin-4-ones may have important pharmaceutical activities.
Bower topic group at the university of Bristol 2016 with [ Rh (cod) Cl]2As catalyst, with P (3,5- (CF)3)2C6H3)3The ring-opening and ring-increasing reaction is successfully realized in benzonitrile by ring opening of cyclopropyl group for ligand and sodium sulfate as additives, and the reaction yield reaches 72 percent (Megan H.Shaw et al.tetrahedron 2016,72, 2731-.
Linlili subject group of Sichuan university in 2020 takes scandium trifluoromethanesulfonate as Lewis acid catalyst, and L3-PiPr3As a ligand, the ring-opening reaction of cyclopropane derivatives and 2-mercaptoaniline is successfully realized by cyclopropyl ring opening in 1,1,2, 2-tetrachloroethane by taking lithium chloride as an additive (Chang F et al. chem. Commun.2020,56, 13429-13432).
In the above reports on the cyclopropyl ring-opening ring-increasing reaction, a catalyst such as [ Rh (cod) Cl ] is commonly used]2、Sc(OTf)3And other additives, such as LiCl, Na2SO4。
Disclosure of Invention
The invention provides a method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compounds by cyclopropyl ring opening.
The technical scheme adopted by the invention is as follows: a method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compounds through cyclopropyl ring opening comprises the steps of adding amide, an organic solvent and oxalyl chloride into a reaction container, reacting for 0.5-2 hours at the temperature of 40-80 ℃, then adding cyclopropamidine hydrochloride into the reaction container, heating to enable the temperature in the reaction container to reach 110-130 ℃, reacting for 6-24 hours at the temperature, and separating and purifying after the reaction is finished to obtain target products.
Preferably, the amide has the general formula:
in the general formula, R is selected from any one of alkyl, aryl and heteroaryl.
Preferably, the molar ratio of amide to oxalyl chloride is 1 (1-8).
Preferably, the molar ratio of the amide to the cyprocomiamide hydrochloride is 1 (0.33-1).
Preferably, the organic solvent is one of xylene or toluene.
Preferably, oxalyl chloride is added dropwise to the reaction vessel.
Preferably, the method for separating and purifying comprises the following steps: after the reaction is finished, cooling the reaction liquid to room temperature, carrying out rotary evaporation to remove the organic solvent, and purifying the obtained crude product by column chromatography to obtain the target product.
Compared with the prior art, the invention has the following advantages: compared with the prior similar reaction, the reaction does not need to add a metal catalyst and a ligand except for necessary solvent and reaction bottom, and is promoted to be efficiently carried out by utilizing hydrochloric acid brought by the cyprocoamidine hydrochloride, and meanwhile, the reaction condition of the reaction is mild, green, environment-friendly and safe. In general, the reaction is environment-friendly, the operation is simple and easy, the product yield is high, and the product has potential medicinal value.
Drawings
FIG. 1 is tetrahydropyrrolo [1,2-a ] prepared in example 1]Process for preparing 2-phenyl-1, 3, 5-triazin-4-ones1H NMR spectrum;
FIG. 2 is tetrahydropyrrolo [1,2-a ] prepared in example 1]Process for preparing 2-phenyl-1, 3, 5-triazin-4-ones13CNMR spectrogram;
FIG. 3 is tetrahydropyrrolo [1,2-a ] prepared in example 2]Process for preparing 2- (4-fluorophenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 4 is tetrahydropyrrolo [1,2-a ] prepared in example 2]Process for preparing 2- (4-fluorophenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 5 is a tetrahydropyrrolo [1,2-a ] prepared in example 3]Process for preparing 2- (4-trifluoromethylphenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 6 is tetrahydropyrrolo [1,2-a ] prepared in example 3]Process for preparing 2- (4-trifluoromethylphenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 7 is tetrahydropyrrolo [1,2-a ] prepared in example 4]Process for preparing 2- (4-chlorophenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 8 is tetrahydropyrrolo [1,2-a ] prepared in example 4]Process for preparing 2- (4-chlorophenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 9 is a tetrahydropyrrolo [1,2-a ] prepared in example 5]Process for preparing 2- (3-chlorophenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 10 is a tetrahydropyrrolo [1,2-a ] prepared in example 5]Process for preparing 2- (3-chlorophenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 11 is a tetrahydropyrrolo [1,2-a ] prepared in example 6]Process for preparing 2- (4-bromophenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 12 is a tetrahydropyrrolo [1,2-a ] prepared in example 6]Process for preparing 2- (4-bromophenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 13 is a tetrahydropyrrolo [1,2-a ] prepared in example 7]2- (3-methylphenyl) -1Process for preparing, 3, 5-triazin-4-ones1H NMR spectrum;
FIG. 14 is a tetrahydropyrrolo [1,2-a ] prepared in example 7]Process for preparing 2- (3-methylphenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 15 is a tetrahydropyrrolo [1,2-a ] prepared in example 8]Process for preparing 2- (2-thienylphenyl) -1,3, 5-triazin-4-one1H NMR spectrum;
FIG. 16 is a tetrahydropyrrolo [1,2-a ] prepared in example 8]Process for preparing 2- (2-thienylphenyl) -1,3, 5-triazin-4-one13C NMR spectrum;
FIG. 17 is a tetrahydropyrrolo [1,2-a ] prepared in example 9]Process for preparing 2-isopropyl-1, 3, 5-triazin-4-one1H NMR spectrum;
FIG. 18 is a tetrahydropyrrolo [1,2-a ] prepared in example 9]Process for preparing 2-isopropyl-1, 3, 5-triazin-4-one13C NMR spectrum.
Detailed Description
For a better illustration of the invention, it will now be further illustrated with reference to examples.
A cyclopropyl ring opening method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compounds comprises the steps of adding amide and an organic solvent into a reaction container, wherein the organic solvent is selected from one of xylene or toluene, slowly carrying out chassis oxalyl chloride in the reaction container, reacting for 0.5-2 hours at the reaction temperature of 40-80 ℃, adding cyclopropamidine hydrochloride into the reaction container, heating to enable the temperature in the reaction container to reach 110-130 ℃, reacting for 6-24 hours at the temperature, carrying out rotary evaporation to remove the organic solvent after reaction liquid is cooled to the room temperature after the reaction is finished, and carrying out column chromatography purification on the obtained crude product to obtain a target product. Wherein the amide has the general formula:
in the general formula, R is selected from any one of alkyl, aryl and heteroaryl; the molar weight ratio of the used amount of the amide to the used amount of the oxalyl chloride and the used amount of the cyproconazidine hydrochloride is 1 (1-8) to 0.33-1, and the reaction equation is as follows:
example 1
A method for preparing tetrahydropyrrolo [1,2-a ] 2-phenyl-1, 3, 5-triazine-4-ketone with the structural formula as follows:
to a 25mL reaction tube were added 121.1mg (1mmol) of benzamide substrate and 1mL of xylene, followed by slowly dropping 0.508mL of oxalyl chloride, followed by addition of magnetons and stirring reaction in an oil bath at 80 ℃ for 1 hour. 72.0mg (0.6mmol) of cyclopropylamidine hydrochloride are subsequently added and the reaction is stirred in an oil bath at 130 ℃ for 12 h. After the reaction is finished, xylene is removed by rotary evaporation, and the crude product is separated and purified by column chromatography to obtain 117.6mg of a target product with the yield of 92%.
Target product characterization data: yellow solid, Mp:241-245 ℃.1H NMR(400MHz,CDCl3)δ8.43–8.35(m,2H),7.52–7.45(m,1H),7.39(t,J＝7.6Hz,2H),4.17–4.08(m,2H),3.14(t,J＝8.1Hz,2H),2.22(p,J＝8.0Hz,2H).13C NMR(101MHz,CDCl3)δ173.46,155.24,135.09,133.10,129.84,128.59,47.94,32.87,17.96.LRMS(EI):m/z calcd for C12H11N3O[M]+,213；found,213.HRMS(ESI):m/z calcd for C12H12N3O[M+H]+,214.0975；found,214.0986.
The target product was synthesized by the same method as in example 1, using different amides and organic solvents under different reaction conditions, and the reaction results are shown in table 1.
TABLE 1 Synthesis of Tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-ones under different conditions
The foregoing description is only of the preferred embodiments of the present invention, and it should be noted that various changes and modifications can be made by those skilled in the art without departing from the overall concept of the invention, and these should also be considered as the protection scope of the present invention.
Claims (7)
1. A method for preparing tetrahydropyrrolo [1,2-a ]1,3, 5-triazine-4-ketone compounds by cyclopropyl ring opening is characterized in that: adding amide, an organic solvent and oxalyl chloride into a reaction vessel, reacting for 0.5-2h at the reaction temperature of 40-80 ℃, then adding cyclopropamidine hydrochloride into the reaction vessel, heating to ensure that the temperature in the reaction vessel reaches 110-130 ℃, reacting for 6-24h at the temperature, and separating and purifying after the reaction is finished to obtain the target product.
2. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 1, characterized in that: the amide has the general formula:
in the general formula, R is selected from any one of alkyl, aryl and heteroaryl.
3. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 1, characterized in that: the molar ratio of the dosage of the amide to the dosage of the oxalyl chloride is 1 (1-8).
4. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 1, characterized in that: the molar ratio of the usage amount of the amide to the usage amount of the cyproconazidine hydrochloride is 1 (0.33-1).
5. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 4, characterized in that: the organic solvent is one of dimethylbenzene or methylbenzene.
6. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 1, characterized in that: oxalyl chloride is added dropwise into the reaction vessel.
7. The process for the ring-opening of cyclopropyl group to produce tetrahydropyrrolo [1,2-a ]1,3, 5-triazin-4-one compounds according to claim 1, characterized in that: the separation and purification method comprises the following steps: after the reaction is finished, cooling the reaction liquid to room temperature, carrying out rotary evaporation to remove the organic solvent, and purifying the obtained crude product by column chromatography to obtain the target product.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115043768A (en) * | 2022-06-20 | 2022-09-13 | 新乡市润宇新材料科技有限公司 | Method for synthesizing N-aryl pyrrolidine-2-ketone by acid-promoted ring opening of cyclopropyl |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1049161A (en) * | 1989-06-05 | 1991-02-13 | 第一制药株式会社 | Heterogeneous ring compound with serotonine 2-receptor antagonistic activity |
| JPH0454184A (en) * | 1990-06-20 | 1992-02-21 | Dai Ichi Seiyaku Co Ltd | 3-substituted condensed triazine derivative |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1049161A (en) * | 1989-06-05 | 1991-02-13 | 第一制药株式会社 | Heterogeneous ring compound with serotonine 2-receptor antagonistic activity |
| JPH0454184A (en) * | 1990-06-20 | 1992-02-21 | Dai Ichi Seiyaku Co Ltd | 3-substituted condensed triazine derivative |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115043768A (en) * | 2022-06-20 | 2022-09-13 | 新乡市润宇新材料科技有限公司 | Method for synthesizing N-aryl pyrrolidine-2-ketone by acid-promoted ring opening of cyclopropyl |
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