CN103172636A - Pyridine-quinazolinone compound and preparation method thereof - Google Patents

Pyridine-quinazolinone compound and preparation method thereof Download PDF

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CN103172636A
CN103172636A CN2013100792928A CN201310079292A CN103172636A CN 103172636 A CN103172636 A CN 103172636A CN 2013100792928 A CN2013100792928 A CN 2013100792928A CN 201310079292 A CN201310079292 A CN 201310079292A CN 103172636 A CN103172636 A CN 103172636A
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CN103172636B (en
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许斌
孙杰
刘秉新
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University of Shanghai for Science and Technology
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Abstract

The invention relates to a pyridino-quinazolinone compound and a preparation method thereof. The structural formula of the compound is shown in the specification, wherein R1=-Ome or H; and R2=-H, -Me, -Ph, -CO2Et, or-Br. The substituted pyridino-quinazolinone compound disclosed by the invention is an important pharmaceutical molecular active skeleton and organically synthesized intermediate, and plays an important role in pharmaceutical chemistry. According to the method, raw materials are available, the reaction yield is high, and the applicable scope of a substrate is wide. Conventional solvents are used in reaction, the operation is simple, the conditions are mild, the reaction is environment-friendly, and the reaction yield is up to 95%, and therefore, the pyridine-quinazolinone compound and the preparation method thereof disclosed by the invention are extremely suitable for industrial production.

Description

Pyrido quianzolinones and preparation method thereof
Technical field
The present invention relates to a kind of pyrido quianzolinones and preparation method thereof.
Background technology
Nitrogen heterocyclic ring is a kind of very common pharmacophoric group in the drug research field, is one of important goal of current small-molecule drug research and development.In recent years, in the brand medicine that global sales comes out at the top, mostly has the nitrogen heterocyclic ring skeleton.The physiologically active such as it is antibiotic, antitumor that nitrogen-containing heterocycle compound has, with and in the significance aspect basic theory and applied research, make synthetic this compounds and its chemistry of research and biological nature, become a heat subject of organic chemistry and association area.And 11 H-pyrido [2,1- b] quinazoline-11-ketone is exactly the class in nitrogen heterocyclic ring, they are widely used in field of medicaments.This compounds all demonstrates good biological activity at aspects such as anti-inflammatory, antianaphylaxis, anticonvulsion, anticancer and tranquilizing soporific, hypotensive, cytoprotectives, referring to following document:
[1]?(a)?Schwender,?C.?F.;?Sunday,?B.?R.;?Herzig,?D.?J.? J.?Med.?Chem. 1979,? 22,?114.?(b)?Aziz,?M.?A.?A.;?Daboun,?H.?A.;?Gawad,?S.?M.?A.? J.?Prakt.?Chem. 1990,? 332,?610。
[2]?Wolfe,?J.?F.;?Rathman,?T.?L.;?Sleevi,?M.?C.;?Campbell,?J.?A.;?Greenwood,?T.?D.? J.?Med.?Chem.? 1990,? 33,?161。
[3]?Jiang,?J.?B.;?Hesson,?D.?P.;?Dusak,?B.?A.;?Dexter,?D.?L.;?Kang,?G.?J.;?Hamel,?E.? J.?Med.?Chem. 1990,? 33,?1721。
[4]?Buyuktimkin,?S.? Pharmazie 1986,? 40,?393。
[5]?(a)?Yen,?M.?H.;?Sheu,?J.?R.;?Peng,?I.?H.;?Lee,?Y.?M.;?Chern,?J.?W.? J.?Pharm.?Pharmacol. 1996,? 48,?90。
(b)?Matzkies,?F.;?Stechert,?R.;?Rauber,?G.;?Matzkies,?F.,?Jr.;?Drescher,?U.? Arzneim.-Forsch. 1989,? 39,?1171。
[6]?Boehringer?Ingelheim?Int. Patent:?Ger.?Offen.?DE?390639,?1989。
Some important natural alkaloids also contain pyrido quinazolinone skeleton, as evodiamine.Evodiamine belongs to indoles alkaloid, is considered to the main pharmacodynamics composition of evodia alkaloid, has that easing pain and diminishing inflammation, antihypertensive diuretic, contraction segmental bronchus, regulate body temperature, fat-reducing, expelling parasite are antibiotic, a central excitation, the effect such as antitumor, referring to following document:
[7]?Chu,?J.?H.? Sci.?Rec.?(China) 1951,? 4,?279;? Chem.?Abstr. 1952,? 46,?11589b。
[8] Dou Changgui. Chinese medicinal materials 2003, 26, 295.
[9] Li Yuanjian. The Chinese Pharmacological circular 2003, 19, 1084.
[10] Wu Lijun. China's combination of Chinese tradiational and Western medicine magazine 2004, 24, 169.
Because this type of structural compounds has excellent pharmacologically active, thereby caused biological medicine researchist's very big interest.Derivative research take quianzolinones as the basis becomes focus.Therefore, develop the novel method of the efficient pyridine synthesis of a kind of energy and quianzolinones, have great importance.It not only can be for pyrido quinazolinone analog derivative provides important synthetic intermediate, and synthetic pyrido quianzolinones itself also can be for the physiologically active screening simultaneously.
Figure 2013100792928100002DEST_PATH_IMAGE001
At present, the pyridine synthesis of reporting in document and the method for quinazolinone mainly contain following several:
(1) aniline reaction of dichloropyridine and ester group replacement.But this class reaction have difficulties on the suitability of substrate, and yield is very low due to the restriction that is subject to the substrate source.
Figure 787054DEST_PATH_IMAGE002
(2) 2-bromopyridine and anthranilic acid under salt of wormwood, copper powder effect, obtain the pyrido quinazolinone.But this reaction conditions is harsher, needs higher temperature of reaction.
(3) PA and 0-chloro-benzoic acid pyridine synthesis and quinazolinone under copper sulfate, salt of wormwood, microwave catalysis.But this synthetic method has certain reaction limitation, is unfavorable for suitability for industrialized production.
Figure 991770DEST_PATH_IMAGE004
(4) take PA and adjacent bromo benzyl bromo as raw material, pyridine synthesis and quinazolinone under cuprous iodide, cesium carbonate, part effect.But the reaction reagent of this synthetic method is expensive, raw material is difficult for obtaining, and is confined to the minority substrate, has limited its application in organic synthesis and chemical industry.
Figure DEST_PATH_IMAGE005
In sum, the method for preparing the pyrido quianzolinones has a lot, but the raw material of these reactions is difficult to obtain, and needs the synthesis step through more complicated; Reaction raw materials limitation in some reaction is larger, and reaction yield is lower, and reaction reagent costliness and reaction conditions are comparatively harsh etc.
Summary of the invention
One of purpose of the present invention is to provide a kind of pyrido quianzolinones.
Two of purpose of the present invention is to provide the preparation method of this compound.
For achieving the above object, the reaction mechanism that the inventive method adopts is:
Figure 879086DEST_PATH_IMAGE006
Wherein: R 1=-OMe ,-H;
R 2?=?-H，-Me，-Ph，-CO 2Et，-Br。
According to above-mentioned reaction mechanism, the present invention has adopted following technical scheme:
A kind of pyrido quianzolinones is characterized in that the structural formula of this compound is:
Figure DEST_PATH_IMAGE007
Wherein: R 1=OMe, H;
R 2?=?H， o-Me， m-Me， p-Ph， m-Ph， o-CO 2Et， m-Br， p-Me.
A kind of method for preparing the pyrido quianzolinones of above-mentioned replacement, it is characterized in that the method has following steps: with the picolinamide that replaces and Potassium ethanoate, additive by 1:(2.0～5.0): the mol ratio of (1.0～5.0) is dissolved in N, in dinethylformamide, and add the cuprous iodide and 1 of catalyst levels, the 10-phenanthroline is 90～100 oAt the C temperature, stirring reaction to reaction raw materials disappears; Filter, get crude product after desolventizing; This crude product is purified, namely obtains the corresponding pyrido quianzolinones that replaces; The structural formula of the picolinamide of described replacement is:
Figure 485648DEST_PATH_IMAGE008
Described additive is: quaternary ammonium compound.
Above-mentioned quaternary ammonium compound is: tetrabutylammonium chloride, Tetrabutyl amonium bromide, tetrabutylammonium iodide, 4-butyl ammonium hydrogen sulfate, tetrabutylammonium acetate ammonium or tetramethyl ammonium chloride.
The pyrido quianzolinones of the replacement that the present invention relates to is active skeleton and the organic synthesis intermediate of the important drug molecule of a class, occupies an important position in pharmaceutical chemistry.
The inventive method raw material is easy to get, and reaction yield is high, wide application range of substrates.Use conventional solvent in reaction, simple to operate, mild condition, reaction environmental protection, reaction yield reaches as high as 95%, is fit to very much industrial production.
Embodiment
Embodiment one: 11 H-pyrido [2,1- b] quinazoline-11-ketone
11 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 14.6 gram 2-(2-bromophenyl)- N-(pyridine-2-yl) ethanamide, 2.7 grams 1, the 10-phenanthroline, 1.3 gram cuprous iodides, 20 gram Potassium ethanoates, 20 gram tetrabutylammonium chlorides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(pyridine-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 9.3 grams 11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 95%.Fusing point: 208-210 ℃.
-1 1698,?1641,?1527,?1456,?764.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.86?(d,? J?=?7.0?Hz,1H),?8.43?(d,? J?=?8.0?Hz,1H),?7.84-7.76?(m,?2H),?7.50-7.48?(m,?3H),?6.86-6.83?(m,?1H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?159.0,?148.6,?147.7,?135.1,?134.1,?127.3,?126.9,?126.7,?126.3,?125.2,?116.3,?112.5.
LC-MS?(ESI)?m/z:?197?[M +H].
Raw material 2-(2-bromophenyl)- NThe following step of synthetic employing of-(pyridine-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids, 23 gram dicyclohexylcarbodiimide, 10.5 gram PAs, 200 milliliters of methylene dichloride, stirring at room 24 hours in 250 milliliters of round-bottomed flasks; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 24.3 gram 2-(2-bromophenyl)- N-(pyridine-2-yl) ethanamide, productive rate is 90%.Fusing point: 116-118 ℃.
-1 3250,?2913,?1681,?1577,?1533,?1462,?1294,?741.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.23-8.21?(m,?2H),?8.16?(br?,1H),?7.70-7.67?(m,?1H),7.61?(d,? J?=?8.0?Hz,1H),?7.40?(dd, ?J?=?7.5,?1.5?Hz,?1H),?7.33?(t,? J?=?7.5?Hz,1H),?7.19?(td, ?J?=?7.5,?1.5?Hz,?1H),?7.03-7.01?(m,?1H),?3.91?(s,?2H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.4,?151.2,?147.3,?138.7,?134.0,?133.2,?131.8,?129.4,?128.1,?125.1,?120.0,?114.3,?45.0.
LC-MS?(ESI)?m/z:?293?[M +H?( 81Br)],?291?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 13H 12BrN 2O?[M +H] +?291.0128;?Found:?291.0131.
Embodiment two: 6-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone
6-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 15.3 gram 2-(2-bromophenyl)- N-(3-picoline-2-yl) ethanamide, 2.9 grams 1, the 10-phenanthroline, 1.6 gram cuprous iodides, 15 gram Potassium ethanoates, 22 gram Tetrabutyl amonium bromides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(3-picoline-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 9.1 gram 6-methyl isophthalic acids 1 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 87%.Fusing point: 128-130 ℃.
-1 ?1699,?1641,?1530,?1456,?764.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.78?(d,? J?=?7.5?Hz,1H),?8.42?(d,? J?=?8.0?Hz,1H),?7.84-7.81?(m,?2H),?7.47-7.43?(m,?1H),?7.35?(d,? J?=?8.5?Hz,1H),?6.76?(t,? J?=?7.0?Hz,1H),?2.58?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?159.4,?148.0,?147.5,?134.9,?134.4,?132.5,?127.3,?127.2,?125.2,?124.9,?116.0,?112.2,?18.7.
LC-MS?(ESI)?m/z:?211?[M +H].
Raw material 2-(2-bromophenyl)- NThe following step of synthetic employing of-(3-picoline-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 12.1 gram 2-amino-3-picoline, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 22.7 gram 2-(2-bromophenyl)- N-(3-picoline-2-yl) ethanamide, productive rate is 80%.Fusing point: 116-118 ℃.
-1 3239,?2927,?2851,?1660,?1576,?1524,?1450,?1338,?1261,?747.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.19?(d,? J?=?3.5?Hz,1H),?7.60-7.54?(m,?2H),?7.41?(dd,? J=?7.5,?1.5?Hz,?1H),?7.30?(td,? J=?7.5,?1.0?Hz,?1H),?7.16?(td,? J=?7.5,?1.5?Hz,?1H),?7.08?(dd,? J=?7.5,?0.5?Hz,?1H),?3.98?(s,?2H),?2.26?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.7,?157.3,?149.6,?145.4,?140.0,?134.8,?133.0,?132.0,?129.1,?127.9,?125.2,?121.7,?44.0,?18.3.
LC-MS?(ESI)?m/z:?307?[M +H?( 81Br)],?305?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 14H 14BrN 2O?[M +H] +?305.0284;?Found:?305.0289.
Embodiment three: 11-oxygen-11 H-pyrido [2,1- b] quinazoline-6-carboxylic acid, ethyl ester
11-oxygen-11 H-pyrido [2,1- b] quinazoline-following step of 6-carboxylic acid, ethyl ester employing: 1. add 18.2 gram 2-(2-(2-bromophenyl) acetamido) Nikithan in 250 milliliters of round-bottomed flasks, 2.9 gram 1, the 10-phenanthroline, 1.6 gram cuprous iodide, 15 gram Potassium ethanoates, 22 gram tetrabutylammonium iodides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(2-(2-bromophenyl) acetamido) Nikithan; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 7.4 gram 11-oxygen-11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-6-carboxylic acid, ethyl ester, productive rate is 55%.Fusing point: 118-120 ℃.
-1 ?1724,?1700,?1536,?1287,?763.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.97?(dd,? J=?7.5,?1.0?Hz,?1H),?8.43?(d,? J?=?9.0?Hz,1H),?7.86-7.85?(m,?3H),?7.52-7.49?(m,?1H),?6.87?(t,? J?=?7.0?Hz,1H),?4.51?(q,? J?=?7.0?Hz,2H),?1.46?(t,? J?=?7.0?Hz,3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?165.1,?158.8,?147.9,?144.5,?135.6,?135.3,?129.4,?129.4,?127.8,?127.2,?126.0,?116.4,?111.0,?62.1,?14.3.
LC-MS?(ESI)?m/z:?269?[M +H].
HRMS:?m/z?calcd?for?C 15H 13N 2O 3?[M +H]269.0921;?Found:?269.0925.
The following step of synthetic employing of raw material 2-(2-(2-bromophenyl) acetamido) Nikithan: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 18.5 gram 2-amino-nicotinic acid ethyl ester, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 20.5 gram 2-(2-(2-bromophenyl) acetamido) Nikithan, productive rate is 61%.Fusing point: 116-118 ℃.
-1 3245,?2929,?2850,?1667,?1585,?1496,?1294,?1239,?739.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ10.90?(s,1H),?8.55?(dd,? J=?5.0,?2.0?Hz,?1H),?8.07?(dd,? J=?8.0,?2.0?Hz,?1H),?7.61?(dd,? J=?8.0,?1.0?Hz,?1H),?7.42?(dd,? J=?7.5,?1.5?Hz,?1H),?7.36?(td,? J=?7.5,?1.0?Hz,?1H),?7.30?(dd,? J=?7.5,?5.0?Hz,?1H),?7.22?(td,? J=?8.0,?2.0?Hz,?1H),?4.14?(q,? J=?7.0?Hz,?2H),?3.95?(s,?2H),?1.21?(t,? J=?7.0?Hz,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ169.1,?166.4,?151.4,?149.1,?139.4,?135.6,?132.7,?132.6,?129.4,?128.1,?125.1,?120.4,?120.2,?61.2,?43.2,?14.5.
LC-MS?(ESI)?m/z:?365?[M +H?( 81Br)],?363?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 16H 16BrN 2O 3?[M +H] +?363.0339;?Found:?363.0349.
Embodiment four: 7-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone
7-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 15.3 gram 2-(2-bromophenyl)- N-(4-picoline-2-yl) ethanamide, 2.9 grams 1, the 10-phenanthroline, 1.6 gram cuprous iodides, 23 gram Potassium ethanoates, 22 gram 4-butyl ammonium hydrogen sulfates, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(4-picoline-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 8.3 gram 7-methyl isophthalic acids 1 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 79%.Fusing point: 150-152 ℃.
-1 ?1702,?1652,?1530,?1456,?767.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.81?(d,? J?=?7.5?Hz,1H),?8.42?(d,? J?=?8.0?Hz,1H),?7.84-7.82?(m,2H),?7.47-7.43?(m,2H),?6.77?(d,? J?=?7.0?Hz,1H),?2.44?(s,3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.8,?147.7,?146.6,?135.2,?127.4,?127.4,?126.3,?126.1,?124.9,?123.3,?115.8,?115.8,?18.3.
LC-MS?(ESI)?m/z:?211?[M +H].
Raw material 2-(2-bromophenyl)- NThe following step of synthetic employing of-(4-picoline-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 12.1 the gram 2-AMINO-4-PICOLINE, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 19.8 gram 2-(2-bromophenyl)- N-(4-picoline-2-yl) ethanamide, productive rate is 70%.Fusing point: 118-120 ℃.
-1 3247,?2923,?2850,?1689,?1577,?1541,?1416,?1331,?744.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.44?(br,?1H),?8.09-8.08?(m,?2H),?7.60?(dd, ?J?=?8.0,?1.5?Hz,?1H),?7.39?(dd, ?J?=?7.5,?1.5?Hz,?1H),?7.32?(td, ?J?=?7.5,?1.0?Hz,?1H),?7.18?(td, ?J?=?8.0,?1.5?Hz,?1H),?6.87-6.86?(m,1H),?3.90?(s,?2H),?2.35?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.5,?151.6,?150.2,?147.1,?134.3,?133.1,?131.8,?129.3,?128.0,?125.1,?121.1,?115.0,?44.8,?21.4.
LC-MS?(ESI)?m/z:?307?[M +H?( 81Br)],?305?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 14H 14BrN 2O?[M +H] +?305.0284;?Found:?305.0280.
Embodiment five: 7-phenyl-11 H-pyrido [2,1- b] quinazoline-11-ketone
7-phenyl-11 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 18.4 gram 2-(2-bromophenyl)- N-(4-phenylpyridine-2-yl) ethanamide, 2.9 grams 1, the 10-phenanthroline, 1.6 gram cuprous iodides, 15 gram Potassium ethanoates, 22 gram tetrabutylammonium acetate ammoniums, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(4-phenylpyridine-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 11.2 gram 7-phenyl-11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 82%.Fusing point: 146-148 ℃.
-1 ?1689,?1647,?1531,?1454,?757,?689.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.88?(d,? J?=?7.5?Hz,1H),?8.40?(d,? J?=?8.0?Hz,1H),?7.82-7.69?(m,?5H),?7.50-7.41?(m,4H),?7.13?(d,? J?=?7.5?Hz,1H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.8,?148.8,?147.9,?146.2,?136.3,?135.2,?130.0,?129.3,?127.4,?126.9,?126.8,?126.7,?125.1,?121.8,?116.1,?112.3.
LC-MS?(ESI)?m/z:?273?[M +H].
HRMS:?m/z?calcd?for?C 18H 13N 2O?[M +H]?273.1022;?Found:?273.1035.
The following step of synthetic employing of raw material 2-(2-bromophenyl)-N-(4-phenylpyridine-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 15.8 gram 4-phenylpyridine-2-amine, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product is with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying obtains 30 gram 2-(2-bromophenyls)-N-(4-phenylpyridine-2-yl) ethanamide, and productive rate is 88%.Fusing point: 142-144 ℃.
-1 3251,?2929,?1692,?1559,?1408,?1223,?763,?746.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.85?(br,1H),?8.58?(s,1H),?8.31?(d,? J?=?5.0?Hz,1H),?7.70?(d,? J?=?6.5?Hz,2H),?7.63?(d,? J?=?8.0?Hz,1H),?7.48-7.43?(m,4H),?7.35?(t,? J?=?7.5?Hz,1H),?7.31-7.29?(m,1H),?,?7.21?(t,? J?=?7.0?Hz,1H),?3.97?(s,?2H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.6,?152.0,?151.2,?147.7,?137.9,?134.1,?133.2,?131.9,?129.4,?129.3,?129.0,?128.1,?127.2,?125.1,?118.1,?112.1,?45.0.
LC-MS?(ESI)?m/z:?369?[M +H?( 81Br)],?367?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 19H 16BrN 2O?[M +H] +?367.0441;?Found:?367.0447.
Embodiment six: 8-phenyl-11 H-pyrido [2,1- b] quinazoline-11-ketone
8-phenyl-11 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 18.4 gram 2-(2-bromophenyl)- N-(5-phenylpyridine-2-yl) ethanamide, 2.9 grams 1, the 10-phenanthroline, 1.7 gram cuprous iodides, 20 gram Potassium ethanoates, 18 gram tetramethyl ammonium chlorides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(5-phenylpyridine-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 11.7 gram 8-phenyl-11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 86%.Fusing point: 148-150 ℃.
-1 ?1686,?1552,?1532,?1457,?778,?766.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?9.05?(s,1H),?8.44?(d,? J?=?8.0?Hz,1H),?7.83-7.77?(m,?3H),?7.62?(d,? J?=?7.0?Hz,2H),?7.57?(d,? J?=?9.5?Hz,1H),?7.49-7.44?(m,?3H),?7.40?(d,? J?=?7.0?Hz,1H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.9,?148.3,?146.8,?135.8,?135.1,?134.7,?129.3,?128.5,?127.4,?126.9,?126.6,?126.4,?126.4,?125.3,?123.4,?116.2.
LC-MS?(ESI)?m/z:?273?[M +H].
HRMS:?m/z?calcd?for?C 18H 13N 2O?[M +]273.1022;?Found:?273.1020.
Raw material 2-(2-bromophenyl)-N-(5-phenylpyridine-2-yl) the following step of synthetic employing of ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 15.8 gram 5-phenylpyridine-2-amine, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product is with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying obtains 27.8 gram 2-(2-bromophenyls)-N-(5-phenylpyridine-2-yl) ethanamide, productive rate is 81%.Fusing point: 138-140 ℃.
-1 3256,?2925,?1692,?1586,?1523,?1469,?768,?741.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.45?(d,? J?=?2.5?Hz,1H),?8.43?(br,1H),?8.33?(d,? J?=?8.5?Hz,1H),?7.94?(dd, ?J?=?8.5,?2.5?Hz,?1H),?7.63?(dd, ?J?=?8.0,?1.0?Hz,?1H),?7.54-7.34?(m,7H),?7.21?(td, ?J?=?7.5,?1.5?Hz,?1H),?3.96?(s,?2H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.4,?150.5,?145.7,?137.3,?137.0,?134.1,?133.2,?133.1,?131.8,?129.4,?129.1,?128.1,?127.9,?126.8,?125.1,?114.2,?45.0.
LC-MS?(ESI)?m/z:?369?[M +H?( 81Br)],?367?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 19H 16BrN 2O?[M +H] +?367.0441;?Found:?367.0442.
Embodiment seven: 2-methoxyl group-11 H-pyrido [2,1- b] quinazoline-11-ketone
2-methoxyl group-11 H-pyrido [2,1- b] preparation of quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 16.1 gram 2-(2-bromo-5-p-methoxy-phenyl)- N-(pyridine-2-yl) ethanamide, 3.0 grams 1, the 10-phenanthroline, 1.8 gram cuprous iodides, 16 gram Potassium ethanoates, 18 gram tetramethyl ammonium chlorides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromo-5-p-methoxy-phenyl)- N-(pyridine-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 9.9 gram 2-methoxyl groups-11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 88%.Fusing point: 158-160 ℃.
-1 1694,?1642,?1545,?1482,?1375,?1022,?762.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.86?(d,? J?=?7.0?Hz,1H),?7.75-7.72?(m,?2H),?7.54-7.46?(m,?3H),?6.88-6.85?(m,?1H),?3.94?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.5,?157.4,?146.0,?143.2,?133.3,?128.3,?127.0,?126.4,?126.0,?116.7,?112.8,?105.2,?55.9.
LC-MS?(ESI)?m/z:?227?[M +H].
Raw material 2-(2-bromo-5-p-methoxy-phenyl)- NThe following step of synthetic employing of-(pyridine-2-yl) ethanamide: 1. add 22.8 gram 2-bromo-5-methoxyphenylacetic acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 10.5 the gram PA, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 23.5 gram 2-(2-bromo-5-p-methoxy-phenyl)- N-(pyridine-2-yl) ethanamide, productive rate is 79%.Fusing point: 136-138 ℃.
-1 246,?2934,?2851,?1690,?1582,?1533,?1437,?1309,?1245,?1014,?776.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.70?(br,1H),?8.28?(d,? J?=?8.5?Hz,1H),?8.22?(dd,? J=?5.0,?1.0?Hz,?1H),?7.78-7.74?(m,?1H),?7.48?(d,? J?=?9.0?Hz,1H),?7.08-7.06?(m,?1H),?6.95?(d,? J?=?3.0?Hz,1H),?6.75?(dd,? J=?9.0,?3.0?Hz,?1H),?3.90?(s,?2H),?3.80?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.3,?159.3,?151.2,?147.3,?138.8,?134.8,?133.8,?120.0,?117.3,?115.3,?115.3,?114.3,?55.5,?45.2.
LC-MS?(ESI)?m/z:?323?[M +H?( 81Br)],?321?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 14H 14BrN 2O 2?[M +H] +?321.0233;?Found:?321.0242.
Embodiment eight: 2-methoxyl group-6-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone
2-methoxyl group-6-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 16.8 gram 2-(2-bromo-5-p-methoxy-phenyl)- N-(3-picoline-2-yl) ethanamide, 3.0 grams 1, the 10-phenanthroline, 1.8 gram cuprous iodides, 24.5 gram Potassium ethanoates, 28 gram 4-butyl ammonium hydrogen sulfates, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromo-5-p-methoxy-phenyl)- N-(3-picoline-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 8.4 gram 2-methoxyl group-6-methyl isophthalic acids 1 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 70%.Fusing point: 132-134 ℃.
-1 1682,?1640,?1521,?1486,?1383,?1028,?762.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.80?(d,? J?=?7.5?Hz,1H),?7.81?(d,? J?=?8.5?Hz,1H),?7.74?(d,? J?=?2.5?Hz,1H),?7.48-7.86?(m,?1H)?,?7.33?(d,? J?=?6.0?Hz,1H),?6.78?(t,? J?=?7.0?Hz,1H),?3.96?(s,?3H),?2.60?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?159.1,?157.2,?145.9,?143.3,?134.5,?131.0,?129.2,?126.5,?124.6,?116.5,?112.7,?104.9,?55.8,?18.6.
LC-MS?(ESI)? m/z:? ?241?[M +H].
HRMS:?m/z?calcd?for?C 14H 12N 2O 2?[M +]240.0899;?Found:?240.0900.
Raw material 2-(2-bromo-5-p-methoxy-phenyl)- NThe following step of synthetic employing of-(3-picoline-2-yl) ethanamide: 1. add 22.8 gram 2-bromo-5-methoxyphenylacetic acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 12.1 gram 2-amino-3-picoline, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 23.3 gram 2-(2-bromo-5-p-methoxy-phenyl)- N-(3-picoline-2-yl) ethanamide, productive rate is 75%.Fusing point: 164-166 ℃.
-1 ?3326,?2930,?2851,?1664,?1575,?1528,?1449,?1338,?1245,?1088,?802.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.47?(br,1H),?8.18?(d,? J?=?4.0?Hz,1H),?7.53?(d,? J?=?7.5?Hz,1H),?7.45?(d,? J?=?9.0?Hz,1H),?7.07?(dd,? J=?7.5,?5.0?Hz,?1H),?6.95?(d,? J?=?3.0?Hz,1H),?6.71?(dd,? J=?9.0,?3.0?Hz,?1H),?3.91?(s,?2H),?3.75?(s,?3H),?2.25?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.5,?159.2,?157.0,?149.3,?145.4,?140.1,?135.5,?133.6,?121.8,?117.3,?115.4,?115.2,?55.5,?44.5,?18.2.
LC-MS?(ESI)?m/z:?337?[M +H?( 81Br)],?335?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 15H 16BrN 2O 2?[M +H] +?335.0390;?Found:?335.0401.
Embodiment nine: 7-bromo-11H-pyrido [2,1-b] quinazoline-11-ketone
7-bromo-11 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 18.5 gram 2-(2-bromophenyl)- N-(4-bromopyridine-2-yl) ethanamide, 3.0 grams 1, the 10-phenanthroline, 1.8 gram cuprous iodides, 24.5 gram Potassium ethanoates, 25 gram tetrabutylammonium acetate ammoniums, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(4-bromopyridine-2-yl) ethanamide disappears; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 7.8 gram 7-bromo-11 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 57%.Fusing point: 174-176 ℃.
-1 1687,?1625,?1546,?1466,?762.
1 H?NMR?(CDCl 3 ,?500?MHz):?8.66?(d,? J?=?7.5?Hz,1H),?8.37?(dd, ?J?=?8.0,?1.5?Hz,?1H),?7.83-7.80?(m,?1H),?7.72?(d,? J?=?8.0?Hz,1H),?7.66?(d,? J?=?3.0?Hz,1H),?7.48-7.44?(m,1H),?6.88?(dd, ?J?=?7.5,?2.0?Hz,?1H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.6,?148.4,?146.9,?135.4,?129.8,?127.8,?127.4,?127.2,?127.0,?125.7,?116.6,?116.3.
LC-MS?(ESI)?m/z:?277?[M +H?( 81Br)],?275?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 12H 8BrN 2O?[M +H]274.9815;?Found:?274.9818.
Raw material 2-(2-bromophenyl)- NThe following step of synthetic employing of-(4-bromopyridine-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 19.3 gram 2-amino-4-bromopyridine, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 20.6 gram 2-(2-bromophenyl)- N-(4-bromopyridine-2-yl) ethanamide, productive rate is 60%.Fusing point: 168-170 ℃.
-1 3235,?2913,?1694,?1575,?1397,?1250,?739.
1 H?NMR?(DMSO ,?500?MHz):?δ11.04?(s,?1H),?8.31?(s,?1H),?8.25?(d,? J?=?5.5?Hz,1H),?7.61?(d,? J?=?8.0?Hz,1H),?7.42?(d,? J?=?7.0?Hz,1H),?7.37-7.34?(m,?2H),?7.22?(t,? J?=?7.0?Hz,1H),?3.96?(s,?2H).
13 C?NMR?(DMSO ,?125?MHz):?δ169.8,?153.4,?149.8,?135.7,?133.6,?132.8,?132.7,?129.4,?128.1,?125.1,?122.8,?116.3,?43.5.
LC-MS?(ESI)?m/z:?373?[M +H?( 81Br)?( 81Br)],?371?[M +H?( 81Br)( 79Br)],?369?[M +H?( 79Br)( 79Br)].
HRMS:?m/z?calcd?for?C 13H 11Br 2N 2O?[M +H] +?368.9233;?Found:?368.9237.
Embodiment ten: 8-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone
8-methyl isophthalic acid 1 H-pyrido [2,1- b] quinazoline-11-ketone adopts following step: 1. add in 250 milliliters of round-bottomed flasks 15.3 gram 2-(2-bromophenyl)- N-(5-picoline-2-yl) ethanamide, 3.0 grams 1, the 10-phenanthroline, 1.8 gram cuprous iodides, 24.5 gram Potassium ethanoates, 25 gram tetrabutylammonium chlorides, 200 milliliters of DMF are heated to 90～100 ℃.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2-(2-bromophenyl)- N-(5-picoline-2-yl) ethanamide disappears; 2. after reaction finishes, with system with diatomite filtration after, get crude product with the Rotary Evaporators desolventizing; 3. (sherwood oil: ethyl acetate=5: 1) purifying obtains 8.5 gram 8-methyl isophthalic acids 1 to crude product with column chromatography H-pyrido [2,1- b] quinazoline-11-ketone, productive rate is 81%.Fusing point: 148-150 ℃.
-1 1683,?1648,?1547,?1530,?1458,?769.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ?8.69?(s,1H),?8.44?(d,? J?=?8.5?Hz,1H),?7.85-7.80?(m,?2H),?7.54?(d,? J?=?9.5?Hz,1H),?7.48-7.42?(m,2H),?2.37?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ?158.6,?147.8,?146.9,?138.1,?135.1,?127.4,?126.3,?125.3,?125.2,?123.7,?122.8,?116.0,?18.3.
LC-MS?(ESI)?m/z:?211?[M +H].
Raw material 2-(2-bromophenyl)- NThe following step of synthetic employing of-(5-picoline-2-yl) ethanamide: 1. add 20 gram 2-bromo-acids in 250 milliliters of round-bottomed flasks, 23 gram dicyclohexylcarbodiimide, 12.1 gram 2-amino-5-picoline, 200 milliliters of methylene dichloride, stirring at room 24 hours; 2. after reaction finishes, system is got crude product with the Rotary Evaporators desolventizing after with diatomite filtration; 3. crude product with column chromatography (sherwood oil: ethyl acetate=5: 1) purifying, obtain 18.7 gram 2-(2-bromophenyl)- N-(5-picoline-2-yl) ethanamide, productive rate is 66%.Fusing point: 98-100 ℃.
-1 3243,?2919,?2850,?1688,?1591,?1520,?1474,?1300,?739.
1 H?NMR?(CDCl 3 ,?500?MHz):?δ8.59?(br,?1H),?8.17?(d,? J?=?8.5?Hz,1H),?8.05?(d,? J?=?1.5?Hz,1H),7.62?(dd, ?J?=?8.0,?1.0?Hz,?1H),?7.56?(dd, ?J?=?8.5,?2.0?Hz,?1H),?7.42?(dd, ?J?=?8.0,?2.0?Hz,?1H),?7.35?(td, ?J?=?8.5,?1.0?Hz,?1H),?7.20?(td, ?J?=?7.5,?1.5?Hz,?1H),?3.93?(s,?2H),?2.30?(s,?3H).
13 C?NMR?(CDCl 3 ,?125?MHz):?δ168.2,?157.1,?149.2,?147.3,?139.2,?134.3,?133.1,?131.8,?129.3,?128.0,?125.1,?113.9,?44.9,?17.8.
LC-MS?(ESI)?m/z:?307?[M +H?( 81Br)],?305?[M +H?( 79Br)].
HRMS:?m/z?calcd?for?C 14H 14BrN 2O?[M +H] +?305.0284;?Found:?305.0296。

Claims (3)

1. pyrido quianzolinones is characterized in that the structural formula of this compound is:
Figure 2013100792928100001DEST_PATH_IMAGE002
Wherein: R 1=-Ome, H;
R 2?=?-H，-Me，-Ph，-CO 2Et，-Br。
2. method for preparing pyrido quianzolinones according to claim 1, it is characterized in that the method has following steps: with the picolinamide that replaces and Potassium ethanoate, additive by 1:(2.0～5.0): the mol ratio of (1.0～5.0) is dissolved in N, in dinethylformamide, and add the cuprous iodide and 1 of catalyst levels, the 10-phenanthroline is 90～100 oAt the C temperature, stirring reaction to reaction raw materials disappears; Filter, get crude product after desolventizing; This crude product is purified, namely obtains the corresponding pyrido quianzolinones that replaces; The structural formula of the picolinamide of described replacement is:
Figure 2013100792928100001DEST_PATH_IMAGE004
Described additive is: quaternary ammonium compound.
3. method according to claim 2, is characterized in that described quaternary ammonium compound is: tetrabutylammonium chloride, Tetrabutyl amonium bromide, tetrabutylammonium iodide, 4-butyl ammonium hydrogen sulfate, tetrabutylammonium acetate ammonium or tetramethyl ammonium chloride.
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CN107698586A (en) * 2017-09-19 2018-02-16 广州大学 It is a kind of that the method for preparing Pyridine-quinazolinocompound compound is catalyzed by copper compound
CN110252351A (en) * 2018-03-01 2019-09-20 苏州大学 Application of the copper catalyst in catalysis 1- pyridyl group benzazolyl compounds, nitrite tert-butyl reaction
CN110252351B (en) * 2018-03-01 2021-12-10 苏州大学 Application of copper catalyst in catalyzing reaction of 1-pyridyl indole compound and tert-butyl nitrite
CN108558872A (en) * 2018-05-17 2018-09-21 浙江工业大学 A kind of 8- substituted-phenyls-quinazolinones and its preparation method and application
CN109608454A (en) * 2018-12-20 2019-04-12 河南师范大学 A kind of new method synthesizing 6 hydrogen-pyridine [1,2-c] quinazoline -6- ketone compounds
CN109608454B (en) * 2018-12-20 2022-09-13 河南师范大学 Novel method for synthesizing 6H-pyridine [1,2-c ] quinazoline-6-ketone compound
CN113973831A (en) * 2020-07-27 2022-01-28 南开大学 Application of camelinine A derivative in treating plant virus and germ diseases
CN113973831B (en) * 2020-07-27 2023-04-28 南开大学 Application of camelnine A derivative in treatment of plant virus germ disease
CN114644655A (en) * 2022-04-19 2022-06-21 湖南农业大学 Preparation method of photocatalytic phosphorylated quinazolinone compound
CN114644655B (en) * 2022-04-19 2023-10-27 湖南农业大学 Preparation method of photocatalytic phosphoryl quinazolinone compound

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