CN103172637A - Pyrimido [1, 2-a] benzimidazole compound and method for preparing same - Google Patents
Pyrimido [1, 2-a] benzimidazole compound and method for preparing same Download PDFInfo
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Abstract
The invention relates to a substituted benzimidazole compound. The substituted benzimidazole compound is characterized by having a structural formula as shown in the specification, R<1> can be a halogen o Ar, and R<2> can be p-Me, p-Cl, p-Br, p-I, p-COOEt, m-Me, o-Me and o-Cl. A method for preparing the substituted benzimidazole compound is characterized by comprising the following steps of: adding substituted N-phenyl-2-aminopyrimidine and PIFA into acetonitrile according to the molar ratio of 1:(1.2-1.8), stirring at room temperature for reaction until the raw materials disappear, removing a solvent to obtain a crude product of reaction, separating the crude product of reaction by column chromatography, and purifying to obtain the corresponding substituted benzimidazole compound. The raw materials are easy to obtain, the environment-friendly reaction yield is up to 97%, the substrate has a wide range of application, the conventional solvent is used during reaction, the operation is simple, the reaction condition is mild, and the method is very suitable for industrial production.
Description
Technical field
The present invention relates to a kind of benzimidazoles compound and preparation method thereof, particularly a kind of Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound and preparation method thereof.
Background technology
Nitrogen heterocyclic ring is a kind of important pharmacophoric group in pharmaceutical chemistry research, becomes one of important goal of current small-molecule drug research and development because majority has biological activity.In the brand medicine of front 25 of global sales in 2007, all 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.
Benzimidazoles compound is widely used for clinical treatment because of various biological activity that its drug molecule of constructing presents, and its effect has hypertension, parasiticide, antibiotic, antimycotic, antiviral, anticancer, analgesia etc.For example, control stomach ulcer medicine rabeprazole and omeprazole; Antihypertensive drug telmisartan and Candesartan; Antiparasitic albendazole and mebendazole etc.Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound has many potential medicine medicinal actives.It has microbiotic and antiarrhythmic performance (referring to Forche Asobo, P.; Wahe, H.; Mbafor, J. T.; Nkengfack, A. E.; Fomum, Z. T.; Sopbue, E. F.; Dopp, D.
J. Chem. Soc., Perkin Trans. 12001,457-461.Also have other physiologically active in medicine, as follows:
Referring to Publication about Document:
1. Lazareno, S.; Popham, A.; Birdsall, N. J. M.
Mol. Pharm. 2002,
62, 1492.
2. Galal, S. A.; Abd El-All, A. S.; Abdallah, M. M.; El-Diwani, H. I.
Bioorg. Med. Chem. Lett. 2009,
19, 2420.
3. Farghaly, T. A.; Abdel Hafez, N. A.; Ragab, E. A.; Awad, H. M.; Abdalla, M. M.
Eur. J. Med. Chem. 2010,
45, 492.
4. E. R. Squibb and Sons, Inc. Patent:
US 4072679 A1, 1978.
Due to the structural singularity of Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound, this compounds can be used as important organic synthesis intermediate.Relevant reaction is exemplified below:
1. Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound that replaces and iodoethane reaction can form the new skeleton of a class after replacing an ethyl on nitrogen-atoms, find that after deliberation it has the effect of inhibition center neural system and anti-inflammatory agent.Referring to: Lin, H.; Erhard, K.; Hardwicke, M. A.; Luengo, J. I.; Mack, J. F.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C. M.; Sanchez, R. M.; Schaber, M. D.; Schulz, M. J.; Spengler, M. D.; Tedesco, R.; Xie, R.; Zeng, J. J.; Rivero, R. A.
Bioorg. Med. Chem 2012,
22, 2230-2234.
2. Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound that replaces is by the modification to its imidazoles nitrogen-atoms, can synthesize a series ofly to the inhibited compound of cancer cells, has very large research potential.Referring to: Da Settimo, A.; Primofiore, G.; Da Settimo, F.; Pardi, G.; Simorini, F.; Marini, A. M.
J. Heterocyclic Chem. 2002,
39, 1007-1011.
3. Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound that replaces and Sodium Nitrite reaction can generate a series of new five-ring products, and this compounds has antiviral activity.Referring to: K ü nstlinger, M.; Breitmaier, E.
Synthesis 1983, 161.
This shows, develop the particularly novel method of Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound of the efficient synthesizing benzimidazole compounds of a kind of energy, have great importance.It can be for developing new a kind of effective means of benzimidazoles drug provision.
The method of synthetic Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound of reporting in document mainly contains following several:
(1) obtain Kui Linpyrimido quinoline [1,2-a] benzoglyoxaline take 2-aminobenzimidazole and alkene ether as raw material, referring to: Zhang, Z.-T.; Qiu, L.; Xue, D.; Wu, J.; Xu, F.-F.
J. Comb. Chem. 2009,
12, 225.This class operation is simple, but productive rate is lower and raw material is very expensive, is unfavorable for industrial production.
Under the highly basic condition, obtain Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound take benzoglyoxaline and ketone as raw material, referring to: Bharate, S. B.; Mahajan, T. R.; Gole, Y. R.; Nambiar, M.; Matan, T. T.; Kulkarni-Almeida, A.; Balachandran, S.; Junjappa, H.; Balakrishnan, A.; Vishwakarma, R. A.
Bioorg. Med. Chem. 2008,
16, 7167.
(2).But should react very large to the restriction of raw material.
(3) under the catalysis of tosic acid, benzoglyoxaline and aldehyde compound obtain Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound
[10]But this reaction has higher requirements to raw material equally.
In sum, the method for preparation Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound has a lot, but the raw material of these reactions is difficult to obtain, and needs the synthesis step through more complicated; In some reaction, the limitation of reaction raw materials is larger, and reaction yield is lower etc.
Summary of the invention
One of purpose of the present invention is to provide a kind of benzimidazoles compound of replacement.
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:
Wherein: R
1=halogen, Ar;
R
2 =
-Me，
-Cl，
-Br，-I，-COOEt；
PIFA is the trifluoracetic acid iodobenzene.
According to above-mentioned reaction mechanism, the present invention has adopted following technical scheme:
A kind of substituted benzimidazole compounds is characterized in that the structural formula of this compound is:
Wherein: R
1=halogen, Ar;
R
2 = -Me，
-Cl，
-Br，-I，-COOEt。
A kind of synthetic method for preparing above-mentioned substituted benzimidazole compounds, it is characterized in that the method has following steps: the N-phenyl that replaces-2-aminopyrimidine, PIFA are joined in acetonitrile by the mol ratio of 1:1.2～1.8, and stirring at room is reacted to raw material and is disappeared; Get crude product after desolventizing; This crude product namely obtains corresponding substituted benzimidazole compounds through separation and purification; The structural formula of the N-phenyl of described replacement-2-aminopyrimidine is:
Substituted benzimidazole compounds of the present invention is the important intermediate of synthesizing benzimidazole compounds, and its preparation 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 are fit to industrial production up to 97% very much.
Embodiment
Embodiment one: the 7-group-4 ethyl formate pyrimidine is the preparation of [1,2-a] benzoglyoxaline also
7-group-4 ethyl formate pyrimidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.7 gram N-(4-group-4 ethyl formate phenyl)-2-amino-pyrimidine in 250 milliliters of round-bottomed flasks, 25.8 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(4-group-4 ethyl formate phenyl)-2-amino-pyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 9.4 gram 7-group-4 ethyl formate pyrimidines, and productive rate is 97%.Fusing point: 260-262 ℃.
-1 3061, 1708, 1605, 1523, 1501, 1453, 1380;
1 H NMR (CDCl 3 , 500 MHz): δ 8.92-8.90 (m, 2H), 8.69 (d,
J = 0.5 Hz, 1H), 8.30 (dd,
J = 8.5, 1.5 Hz, 1H), 8.03 (d,
J = 8.5 Hz, 1H), 7.05 (dd,
J = 6.5, 4.5 Hz, 1H), 4.47 (q,
J = 7.0 Hz, 2H), 1.46 (t,
J = 7.5 Hz, 3H);
13 C NMR (CDCl 3 , 125 MHz): δ 166.4, 156.8, 152.3, 147.4, 133.8, 127.6, 126.5, 124.1, 120.1, 113.2, 107.4, 61.3, 14.4;
EI-MS
m/z (%):
241 (75) [M
+], 213 (32), 196 (100), 168 (34);
HRMS (EI): m/z Calcd. for C
13H
11N
3O
2: 241.0851, Found 241.0855.
Synthesizing of raw material N-(4-group-4 ethyl formate phenyl)-2-amino-pyrimidine, referring to: Schulte Ii, J. P.; Tweedie, S. R.
Synlett 2007, 2331.
Embodiment two: the 7-methylpyrimidine is the preparation of [1,2-a] benzoglyoxaline also
7-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.3 gram N-(4-aminomethyl phenyl)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 25.6 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(4-aminomethyl phenyl)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 7.6 gram 7-methylpyrimidines, and productive rate is 82%.Fusing point: 205-206 ℃.
-1 3045, 1606, 1579, 1499, 1452, 1376, 804;
1 H NMR (CDCl 3 , 500 MHz): δ 8.80 (dd,
J = 6.5, 2.0 Hz, 1H), 8.75 -8.74 (m, 1H), 7.89 (d,
J = 8.5 Hz, 1H), 7.69 (s, 1H), 7.39 (dd,
J= 8.0, 1.0 Hz, 1H), 6.92 (dd,
J= 7.0, 4.0 Hz, 1H)，2.56 (s, 3H);
13 C NMR (CDCl 3 , 125 MHz): δ 154.9, 150.1, 142.1, 133.1, 132.4, 128.4, 126.8, 120.1, 110.2, 106.5, 21.92;
EI-MS
m/z (%):
183 (15) [M
+], 95 (100);
HRMS (EI): m/z Calcd. for C
11H
9N
3: 183.0796, Found 183.0791.
Synthesizing of raw material N-(4-aminomethyl phenyl)-2-aminopyrimidine, referring to: Takeuchi, H.; Watanabe, K.
J. Phys. Org. Chem. 1998,
11, 478.
Embodiment three: the 7-bromo pyrimi piperidine is the preparation of [1,2-a] benzoglyoxaline also
7-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 10 gram N-(4-bromophenyl)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 30 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(4-bromophenyl)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 8.1 gram 7-bromo pyrimi piperidines, and productive rate is 81%.Fusing point: 270-272 ℃.
-1 3095, 1625, 1523, 1496, 1458, 583;
1 H NMR (CDCl 3 , 500 MHz): δ 9.51 (dd,
J= 7.0, 2.0 Hz, 1H), 8.86-8.85 (m, 1H), 8.65 (d,
J = 1.5 Hz, 1H), 7.80 (d,
J = 8.5 Hz, 1H), 7.67 (dd,
J= 8.5, 2.0 Hz, 1H), 7.19 (dd,
J = 7.0, 4.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz): δ 157.5, 150.9, 142.8, 136.5, 129.4, 128.4, 121.4, 116.2, 113.5, 107.6;
EI-MS
m/z (%):
249 (95) [M
+ (
81Br)], 247 (100) [M
+ (
79Br)];
HRMS (EI): m/z Calcd. for C
10H
6N
3Br: 246.9745, Found 246.9747.
Synthesizing of raw material N-(4-bromophenyl)-2-aminopyrimidine, referring to: Delvos, L. B.; Begouin, J.-M.; Gosmini, C.
Synlett 2011, 2325.
Embodiment four: the 7-chloropyrimide is the preparation of [1,2-a] benzoglyoxaline also
7-chloropyrimide also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.2 gram N-(4-chloro-phenyl-)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 29 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(4-chloro-phenyl-)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 7.3 gram 7-chloropyrimide, and productive rate is 79%.Fusing point: 319-320 ℃.
-1 3051, 1614, 1524, 1497, 1460, 762;
1 H NMR (CDCl 3 , 500 MHz): δ 9.52 (dd,
J = 6.5, 2.0 Hz, 1H), 8.88-8.86 (m, 1H), 8.54 (d,
J = 2.0 Hz, 1H), 7.87 (d,
J = 9.0 Hz, 1H), 7.58 (dd,
J = 9.0, 2.0 Hz, 1H), 7.21 (dd,
J = 6.5, 4.0 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz): δ 157.5, 151.1, 142.6, 136.5, 127.9, 126.9, 125.9, 121.0, 113.3, 107.8;
EI-MS
m/z (%):
205 (33) [M
+ (
37Cl)], 203 (100) [M
+ (
35Cl)], 154 (44);
HRMS (EI): m/z Calcd. for C
10H
6N
3Cl: 203.0250, Found 203.0248.
Synthesizing of raw material N-(4-chloro-phenyl-)-2-aminopyrimidine, referring to: Takeuchi, H.; Watanabe, K.
J. Phys. Org. Chem. 1998,
11, 478.
Embodiment five: the 9-chloropyrimide is the preparation of [1,2-a] benzoglyoxaline also
9-chloropyrimide also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.2 gram N-(2-chloro-phenyl-)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 29 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(2-chloro-phenyl-)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 7.2 gram 9-chloropyrimide, and productive rate is 78%.Fusing point: 262-264 ℃.
-1 3075, 1623, 1598, 1500, 1480, 775;
1 H NMR (CDCl 3 , 500 MHz): δ 9.55 (dd,
J = 7.0, 1.5 Hz, 1H), 8.91-8.90 (m, 1H), 8.29 (d,
J = 8.5 Hz, 1H), 7.63 (d,
J = 8.0 Hz, 1H), 7.40 (t,
J = 8.0 Hz, 1H), 7.23 (dd,
J = 7.0, 4.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz): δ 157.8, 150.8, 141.0, 136.8, 128.5, 126.1, 123.2, 122.3, 112.2, 108.1;
EI-MS
m/z (%):
205 (5) [M
+ (
37Cl)], 203 (14) [M
+ (
35Cl)], 154 (100);
HRMS (EI): m/z Calcd. for C
10H
6N
3Cl: 203.0250, Found 203.0247.
Synthesizing of raw material N-(2-chloro-phenyl-)-2-aminopyrimidine, referring to: Takeuchi, H.; Watanabe, K.
J. Phys. Org. Chem. 1998,
11, 478.
Embodiment six: the 8-methylpyrimidine is the preparation of [1,2-a] benzoglyoxaline also
8-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.3 gram N-(3-aminomethyl phenyl)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 25.6 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(3-aminomethyl phenyl)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product with column chromatography (ethyl acetate) purifying, obtains also [1,2-a] benzoglyoxaline of 7.2 gram 8-methylpyrimidines, and productive rate is 77%.Fusing point: 199-200 ℃.
-1 3047, 1603, 1522, 1503, 1454, 1374, 792;
1 H NMR (CDCl 3 , 500 MHz): δ 8.78 (dd,
J= 7.0, 2.0 Hz, 1H), 8.73-8.72 (m, 1H), 7.77-7.75 (m,2H), 7.21 (d,
J = 8.5 Hz, 1H), 6.89 (dd,
J = 6.5, 4.0 Hz, 1H), 2.55 (s, 3H);
13 C NMR (CDCl 3 , 125 MHz): δ 155.1, 150.4, 144.0, 137.0, 133.3, 124.7, 123.9, 119.8, 110.3, 106.6, 22.13;
EI-MS
m/z (%):
183 (100) [M
+], 143 (82), 95 (87);
HRMS (EI): m/z Calcd. for C
11H
9N
3: 183.0796, Found 183.0795.
Synthesizing of raw material N-(3-aminomethyl phenyl)-2-aminopyrimidine, referring to: Takeuchi, H.; Watanabe, K.
J. Phys. Org. Chem. 1998,
11, 478.
Embodiment seven: the 3-bromo pyrimi piperidine is the preparation of [1,2-a] benzoglyoxaline also
3-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 10 gram N-phenyl-2-amino-5-bromo pyrimi piperidine in 250 milliliters of round-bottomed flasks, 30 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-phenyl-2-amino-5-bromo pyrimi piperidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain also [1,2-a] benzoglyoxaline of 7.5 gram 3-bromo pyrimi piperidines, and productive rate is 75%.Fusing point: 240-242 ℃.
-1 3049, 1594, 1511, 1479, 1450, 558;
1 H NMR (CDCl 3 , 500 MHz): δ 9.93 (d,
J = 2.5 Hz, 1H), 8.87 (d,
J = 2.5 Hz, 1H), 8.33 (d,
J = 8.5 Hz, 1H), 7.86 (d,
J = 8.5 Hz, 1H), 7.58-7.55 (m, 1H), 7.44 (t,
J = 7.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz): δ 156.7, 148.6, 144.2, 136.3, 127.2, 126.9, 122.5, 119.8, 113.4, 101.7;
EI-MS
m/z (%):
249 (93) [M
+ (
81Br)] ,247 (100) [M
+ (
79Br)], 168 (48);
HRMS (EI): m/z Calcd. for C
10H
6N
3Br: 246.9745, Found 246.9741.
Synthesizing of raw material N-phenyl-2-amino-5-bromo pyrimi piperidine, referring to: Array Biopharma Inc. WO2007/146824 A2,
2007.
Embodiment eight: the 7-iodine pyrimidine is the preparation of [1,2-a] benzoglyoxaline also
7-iodine pyrimidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 9 gram N-(4-iodophenyl)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 16 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(4-iodophenyl)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain also [1,2-a] benzoglyoxaline of 5.8 gram 7-iodine pyrimidines, and productive rate is 64%.Fusing point: 328-330 ℃.
-1 3024, 1624, 1523, 1497, 1451, 582;
1 H NMR (CDCl 3 , 500 MHz): δ 9.50 (dd,
J= 6.5, 1.5 Hz, 1H), 8.85 (d,
J = 1.5 Hz, 1H), 8.78 (s, 1H), 7.81 (d,
J = 8.5 Hz, 1H), 7.67 (d,
J = 8.5 Hz, 1H), 7.17 (dd,
J= 6.5, 4.0 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz): δ 157.5, 150.5, 143.2, 136.5, 134.8, 129.0, 121.7, 121.6, 107.8, 84.7;
EI-MS
m/z (%):
295 (100) [M
+], 168 (30);
HRMS (EI): m/z Calcd. for C
10H
6N
3I: 294.9606, Found 294.9604.
Synthesizing of raw material N-(4-iodophenyl)-2-aminopyrimidine, referring to: Toray Industries, Inc. WO2006/68213 A1,
2006
Embodiment nine: the 9-methylpyrimidine is the preparation of [1,2-a] benzoglyoxaline also
9-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: 1. add 9.3 gram N-(2-aminomethyl phenyl)-2-aminopyrimidine in 250 milliliters of round-bottomed flasks, 38.4 gram trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room.Follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials N-(2-aminomethyl phenyl)-2-aminopyrimidine disappearance; 2. after reaction finishes, with getting crude product with the Rotary Evaporators desolventizing after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain also [1,2-a] benzoglyoxaline of 4.9 gram 9-methylpyrimidines, and productive rate is 53%.Fusing point: 195-196 ℃.
-1 3067, 1619, 1597, 1500, 1377, 778;
1 H NMR (CDCl 3 , 500 MHz): δ 8.75-8.74 (m, 1H), 8.72 (dd,
J = 7.0, 2.0 Hz, 1H), 7.69 (d,
J = 8.0 Hz, 1H), 7.36 (d,
J = 7.0Hz, 1H), 7.30 (t,
J = 8.0 Hz, 1H), 6.87 (dd,
J= 6.5, 4.0 Hz, 1H), 2.79 (s, 3H)；
13 C NMR (CDCl 3 , 125 MHz): δ 155.0, 150.0, 143.5, 133.3, 130.8, 126.5, 126.3, 122.0, 107.9, 106.5, 17.1;
EI-MS
m/z (%):
183 (23) [M
+], 154 (100);
HRMS (EI): m/z Calcd. for C
11H
9N
3: 183.0796, Found 183.0793.
Synthesizing of raw material N-(2-aminomethyl phenyl)-2-aminopyrimidine, referring to: Takeuchi, H.; Watanabe, K.
J. Phys. Org. Chem. 1998,
11, 478.
Claims (2)
1. substituted benzimidazole compounds is characterized in that the structural formula of this compound is:
Wherein: R
1=halogen, Ar;
R
2 = -Me，
-Cl，
-Br，-I，-COOEt。
2. one kind prepares the synthetic method of substituted benzimidazole compounds according to claim 1, it is characterized in that the method has following steps: the N-phenyl that replaces-2-aminopyrimidine, trifluoracetic acid iodobenzene are joined in acetonitrile by the mol ratio of 1:1.2～1.8, and stirring at room is reacted to raw material and is disappeared; Get crude product after desolventizing; This crude product namely obtains corresponding substituted benzimidazole compounds through separation and purification; The structural formula of the N-phenyl of described replacement-2-aminopyrimidine is:
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2019533650A (en) * | 2016-09-30 | 2019-11-21 | エピザイム，インコーポレイティド | Substituted fused bicyclic or tricyclic heterocyclic compounds as EHMT2 inhibitors |
| CN112574219A (en) * | 2021-01-31 | 2021-03-30 | 湖北大学 | Synthesis method of benzimidazolopyrimidinone derivative |
| CN113845530A (en) * | 2021-09-08 | 2021-12-28 | 桂林理工大学 | Convenient Michal addition reaction of 2-phenylbenzimidazole [2,1-b ] thiazole |
| US11672800B2 (en) | 2017-04-21 | 2023-06-13 | Epizyme, Inc. | Combination therapies with EHMT2 inhibitors |
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| WO2011119565A1 (en) * | 2010-03-23 | 2011-09-29 | Siemens Medical Solutions Usa, Inc. | Imaging agents for detecting neurological disorders |
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| WO2011119565A1 (en) * | 2010-03-23 | 2011-09-29 | Siemens Medical Solutions Usa, Inc. | Imaging agents for detecting neurological disorders |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019533650A (en) * | 2016-09-30 | 2019-11-21 | エピザイム，インコーポレイティド | Substituted fused bicyclic or tricyclic heterocyclic compounds as EHMT2 inhibitors |
| JP7187449B2 (en) | 2016-09-30 | 2022-12-12 | エピザイム，インコーポレイティド | Substituted Fused Bicyclic or Tricyclic Heterocyclic Compounds as EHMT2 Inhibitors |
| US11672800B2 (en) | 2017-04-21 | 2023-06-13 | Epizyme, Inc. | Combination therapies with EHMT2 inhibitors |
| CN112574219A (en) * | 2021-01-31 | 2021-03-30 | 湖北大学 | Synthesis method of benzimidazolopyrimidinone derivative |
| CN113845530A (en) * | 2021-09-08 | 2021-12-28 | 桂林理工大学 | Convenient Michal addition reaction of 2-phenylbenzimidazole [2,1-b ] thiazole |
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| CN103172637B (en) | 2015-05-27 |
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