CN104829614B - Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound - Google Patents
Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound Download PDFInfo
- Publication number
- CN104829614B CN104829614B CN201510195454.3A CN201510195454A CN104829614B CN 104829614 B CN104829614 B CN 104829614B CN 201510195454 A CN201510195454 A CN 201510195454A CN 104829614 B CN104829614 B CN 104829614B
- Authority
- CN
- China
- Prior art keywords
- pyrrole
- chlorophenyl
- pyridine
- reaction
- cdcl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
A method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds. The 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound is prepared by taking a 2-arylamine-N-aryl pyrrole compound and an aldehyde compound as raw materials, ammonium acetate as a catalyst and PEG-400 as a solvent in one step under a heating condition. After the reaction is finished, the 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound can be obtained through operations such as cooling, suction filtration and separation. The reaction steps are only one step, the process is simple, and the raw materials, the catalyst and the solvent are cheap and easily available chemical raw materials; the reaction has the advantages of high efficiency, simple operation, good functional group compatibility, good regioselectivity, high product yield and the like, and has wide application prospect.
Description
Technical Field
The invention relates to a method for synthesizing 4-hydro-pyrrole [3,2-c ] pyridine-4-ketone compounds, in particular to a method for generating 4-hydro-pyrrole [3,2-c ] pyridine-4-ketone compounds by using ammonium acetate as a catalyst and PEG-400 as a solvent through intermolecular series reaction of 2-arylamino-N-aryl pyrrole compounds and aldehyde compounds under a heating condition. The method has the advantages of wide universality, simple operation, good functional group compatibility, good regioselectivity, high product yield and the like.
Background
The 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound has various biological activities. Further cyclization by functionalized pyrroles is a common method for preparing such compounds. Document beccalali, e.m.; broggini, G.; martinelli, m.; paladino, G.tetrahedron 2005, 61, 1077-1082 takes o-formylpyrrole as raw material, and prepares 4H-pyrrole [3,2-c ] pyridine-4-ketone compounds through three steps of reactions, but another regioselective isomer can be obtained through the reaction at the same time, and the ratio of the two isomers is between 2: 1 and 1: 1. The literature Herz, w.; the target product 4H-pyrrole [3,2-c ] pyridine-4-ketone compound is also obtained by the three-step reaction of Tocker, S.J.Am.chem.Soc.1955, 77, 6353-Buchner 6355, but in the reaction process, phosphorus oxychloride with strong corrosiveness is used as a catalyst. Biblin, g.m.p.; billington, a.; briggs, m.; brown, a.j.; chessell, i.p.; clayton, n.m.; eaterton, a.j.; goldsmith, p.; haslam, c.; johnson, m.r.; mitchell, w.l.; naylor, a.; perboni, a.; slingsby, b.p.; wilson, A.W.J.Med.chem.2009, 52, 5785-. The literature Menichincheri, m.; bargiotti, a.; berthelsen, j.; bertrand, j.a.; bossi, r.; ciavallolla, a.; cirla, a.; cristiani, c.; croci, v.; d' Alessio, r.; fasolini, m.; firorentini, f.; fore, B.; isachi, a.; martina, k.; moliari, a.; montagnoli, a.; orini, p.; orzi, f.; pesenti, e.; pezzetta, d.; pilan, a.; poggesi, i.; roletto, f.; scolaro, a.; tat oa, m; tibolla, m.; valsnaina, b.; varasi, m.; volpi, d.; santocaale, c.; the 4H-pyrrolo [3,2-c ] pyridin-4-one compounds were also obtained by a two-step reaction using a two-component reaction in Vanotti, E.J.Med.chem.2008, 52, 293-one 307, but using strong acids and organic solvents during the reaction. Document Takahata, h.; wang, E. -C.; nakajima, t.; yamazaki, t.chem.pharm.ball.1987, 35, 3139-3145 and Takahata, h.; suzuki, t.; yamazaki, T.heterocycles 1986, 24, 1247-1250-type also used sodium ethoxide as a strong base as a reaction catalyst in the preparation of 4-hydro-pyrrolo [3,2-c ] pyridin-4-one compounds.
The preparation of 4-hydro-pyrrolo [3,2-c ] pyridin-4-ones by further cyclization of pyridine derivatives is another common procedure. Document (a) Livecchi, m.; calvet, g.; schmidt, f.j.org.chem.2012, 77, 5006-; (b) calvet, g.r.; livecchi, m.; schmidt, f.d.r.j.org.chem.2011, 76, 4734-; (c) wedge, m.; savarin, c.g.; bifelice, k.; maligres, p.; hummphrey, g.; reamer, B.; teller, d.m.; hughes, d.org.pro.res.dev.2010, 14, 787-; (d) moustafa, m.m.a.r.; pagenkopf, b.l.org.lett.2010, 12, 3168-; (e) whelligan, D.K.; thomson, d.w.; taylor, d.; hoelder, s.j.org.chem.2009, 75, 11-15; (f) giblin, g.m.p.; billington, a.; briggs, m.; brown, a.j.; chessell, i.p.; clayton, n.m.; eaterton, a.j.; goldsmith, p.; haslam, c.; johnson, m.r.; mitchell, w.l.; naylor, a.; perboni, a.; slingsby, b.p.; this strategy is adopted by Wilson, a.w.j.med.chem.2009, 52, 5785-. Some of the methods adopt a strategy of combining multiple noble metal catalysts for catalysis, strong acid for catalysis or multistep reaction, so that the operation is complicated, the reaction cost is increased, and the method is not favorable for large-scale industrial production.
In addition, there are also some reactions which employ a multi-component one-pot synthesis of 4-hydro-pyrrolo [3,2-c]Strategies for pyridin-4-ones. Literature Sun, x.; wang, c.; li, Z.; zhang, s.; xi, Z.J.Am.chem.Soc.2004, 126, 7172-7173 from the reaction of sildiyne derivatives with trimolecular nitriles to synthesize 4-hydro-pyrrole [3,2-c ]]One-pot multicomponent cascade reaction of pyridine-4-ones is a typical representative. They used Negishi reagent Cp during the reaction2ZrBu2As catalyst for the reaction, this reagent is Cp2ZrCl2And n-butyllithium at-78 deg.C, and is prepared on-site.
In summary, the prior literature methods for the one-step and stepwise synthesis of 4-hydro-pyrrolo [3,2-c ] pyridin-4-one compounds have several disadvantages. In recent years, with the enhancement of the awareness of environmental protection, the improvement of national environmental protection legislation and the enhancement of law enforcement, the production and use of highly toxic, high-energy-consumption and high-pollution chemicals in the chemical industry are increasingly limited, and instead, the production of pollutants is reduced from the source of raw materials and processes until the generation of pollutants is stopped. Therefore, the search for a synthetic method with simple reaction conditions and environmental friendliness is an important direction in the field of production of the compounds.
Disclosure of Invention
The invention takes 2-arylamine-N-aryl pyrrole compounds and aldehyde compounds as raw materials, takes ammonium acetate as a catalyst, and prepares 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds in PEG-400 in one step under the condition of heating. The invention aims to establish a simple, effective and high-selectivity synthesis method of 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds. In order to achieve the purpose, the method provided by the invention is carried out in PEG-400 solvent, and 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds can be obtained in high yield through one-step reaction under the catalysis of ammonium acetate.
The technical scheme adopted by the invention is as follows:
wherein:
the reactant is 2-arylamine-N-aryl pyrrole compound and aldehyde compound;
substituent R1Selected from 4-methylphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl;
substituent R2Selected from 2-chlorophenyl, 3-chlorophenyl, 4-carbethoxyphenyl, 4-methylphenyl, 2-methoxyphenyl;
substituent R3Selected from 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, cyclohexyl;
the catalyst is ammonium acetate;
the reaction solvent is PEG-400;
the reaction is carried out under heating.
In summary, the method of the present invention requires only one reaction step. The catalyst ammonium acetate and the solvent PEG-400 used in the reaction are cheap and easily available chemical products; when 10 times of ammonium acetate catalyst is used, the reaction can achieve good catalytic effect, and the reaction process is simple. In PEG-400, 2-arylamine-N-arylpyrrole compounds and aldehyde compounds are cyclized to generate 4H-pyrrole [3,2-c ] pyridine-4-ketone compounds. In a word, the method has the advantages of few experimental steps, low technical difficulty, high chemical selectivity and easy operation. The method avoids the process of using multi-step reaction and simultaneously avoids the use of toxic and harmful organic solvents. After the reaction is finished, 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone products can be obtained only by adding water to quench the reaction, extracting, carrying out column chromatography and the like. These advantages facilitate the application of the process of the invention to large-scale industrial production.
The specific implementation method comprises the following steps:
the invention is described in detail below by way of examples. Of course, the present invention is not limited to the following examples.
Example 1
To a 25 ml round bottom flask were added N- (4-chlorobenzene) -2-methyl-1- (p-tolyl) -4, 5-dihydro-1 h-pyrrole-3-carboxamide (130 mg, 0.4 mmol), benzaldehyde (46 mg, 0.44 mmol), ammonium acetate (308.3 mg, 4 mmol) and the solvent PEG-400(2 ml), the reaction mixture was heated in an oil bath, the course of the reaction was monitored by LC-MS, the system was naturally cooled to room temperature after the end of the reaction, extracted, separated, dried, and column chromatographically processed to give 5- (4-chlorophenyl) -6-phenyl-1- (p-tolyl) -1, 2, 3, 5, 6, 7-hexahydro-4 h-pyrido [3,2-c ] pyridin-4-one (119 mg, 72%).
5- (4-chlorophenyl) -6-phenyl-1- (p-tolyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 72%, melting point: 181-182 ℃;1H NMR(400MHz，CDCl3)δ7.27-7.16(m，5H)，7.13(d，J＝8.8Hz，2H)，7.06(m，4H)，6.73(d，J＝8.0Hz，2H)，5.11-5.04(m，1H)，3.96-3.88(m，2H)，3.36-3.30(dd，J＝16.8，5.6Hz，1H)，3.08-3.00(m，1H)，2.95-2.86(m，1H)，2.81(d，J＝14.4Hz，1H)，2.25(s，3H).13C NMR(100MHz，CDCl3)δ165.90，140.87，140.45，138.41，134.15，130.60，130.05，128.88，128.66，127.88，126.92，126.70，121.24，62.45，54.29，32.44，25.64，20.89.
5- (3-chlorophenyl) -6-phenyl-1- (p-tolyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 66%, melting point: 73-76 ℃;1H NMR(400MHz，CDCl3)δ7.33-7.26(m，6H)，7.13(t，J＝8Hz，3H)，7.06(t，J＝9.2Hz，2H)，6.79(d，J＝8.4Hz，2H)，5.18-5.17(m，1H)，4.03-3.89(m，2H)，3.40(dd，J＝16.8，6.4Hz，1H)，3.03(t，J＝10.6Hz，1H)，2.99-2.92(m，1H)，2.88(d，J＝15.6Hz，1H)，2.33(s，3H).13C NMR(100MHz，CDCl3)δ165.57，143.67，140.48，138.52，133.71，133.49，129.80，129.20，128.63，127.56，126.44，125.51，124.80，123.14，120.83，62.06，53.71，32.22，25.38，20.67.
ethyl 4- (4-oxo-6-phenyl-1- (p-tolyl) -1, 2, 3, 4, 6, 7-hexahydro-5-hydro-5-pyrrolo [3,2-c ] pyridinyl) benzoate
White solid, yield: 72%, melting point: 143-145 ℃;1H NMR(400MHz，CDCl3)δ7.84(d，J＝8.8Hz，2H)，7.24-7.20(m，6H)，7.18(s，1H)，7.04(d，J＝8.4Hz，2H)，6.70(d，J＝8.4Hz，2H)，5.18(dd，J＝6.4，2.4Hz，1H)，4.28-4.23(m，2H)，3.94-3.84(m，2H)，3.35(dd，J＝16.8，6.0Hz，1H)，3.03-2.94(m，1H)，2.89-2.80(m，2H)，2.25(s，3H)，1.29(t，J＝7.0Hz，3H).13CNMR(100MHz，CDCl3)δ166.25，165.48，146.74，140.46，138.42，133.57，129.83，128.71，127.57，126.35，125.80，123.71，120.82，61.74，60.67，53.70，32.17，25.35，20.72，14.29.
5- (2-methoxyphenyl) -6-phenyl-1- (p-tolyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 18%, melting point: 146-148 ℃;1H NMR(400MHz，CDCl3)δ7.29-7.26(m，5H)，710-7.06(m，4H)，6.76-6.73(m，4H)，5.08(dd，J＝6.4，32Hz，1H)，3.99-3.85(m，2H)，3.73(s，3H)，3.36(dd，J＝16.4，6.8Hz，1H)，3.03-2.88(m，2H)，2.83(dd，J＝16.8，2.4Hz，1H)，2.29(s，3H).13CNMR(100MHz，CDCl3)δ166.05，157.25，140.54，134.93，129.85，128.57，127.59，127.28，126.70，120.93，113.82，62.73，55.34，32.25，25.63，20.72.
5- (4-methoxyphenyl) -6-phenyl-1- (p-tolyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 25%, melting point: 146-147 ℃;1H NMR(400MHz，CDCl3)δ7.29(d，J＝7.2Hz，2H)，7.21(d，J＝7.2Hz，2H)，7.13(d，J＝7.6Hz，2H)，7.08-7.02(m，3H)，6.84-6.81(m，2H)，6.76(d，J＝8.4Hz，2H)，5.11(s，1H)，4.11-4.07(m，2H)，3.73(s，3H)，3.50-3.43(m，2H)，3.15(s，1H)，3.91-2.86(m，1H)，2.31(s，3H).13C NMR(100MHz，CDCl3)δ165.68，153.46，141.09，140.73，138.68，133.26，129.91，129.78，128.60，128.35，127.52，126.52，126.49，120.67，105.54，62.12，53.55，32.28，25.44，20.67.
1, 5-bis (4-chlorophenyl) -6-phenyl-1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 61%, melting point: 203-205 ℃;1H NMR(400MHz，CDCl3)δ7.35-7.27(m，2H)，7.27-7.22(m，5H)，7.19-7.17(m，2H)，7.13-7.10(m，2H)，6.76(d，J＝8.8Hz，2H)，5.15(dd，J＝6.4，3.2Hz，1H)，3.99-3.85(m，2H)，3.41(dd，J＝16.4，6.4Hz，1H)，3.05-2.90(m，2H)，2.86(d，J＝19.2Hz，1H).13C NMR(100MHz，CDCl3)δ165.46，152.16，140.87，140.54，139.83，130.18，129.27，128.70，128.45，128.22，127.66，126.52，126.49，121.13，107.24，62.14，53.19，32.44，25.48.
1- (3-chlorophenyl) -5- (4-chlorophenyl) -6-phenyl-1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 67%, melting point: 192 ℃ to 193 ℃;1H NMR(400MHz，CDCl3)δ7.30-7.26(m，2H)，7.25(d，J＝7.2Hz，3H)，7.20-7.16(m，3H)，7.11(d，J＝8.8Hz，2H)，6.99(d，J＝7.2Hz，1H)，6.79(s，1H)，6.72(d，J＝8.0Hz，1H)，5.14(d，J＝3.2Hz，1H)，3.97-3.87(m，2H)，3.45-3.41(m，1H)，3.01-2.94(m，1H)，2.89(d，J＝15.2Hz，2H).13C NMR(100MHz，CDCl3)δ165.41，151.90，142.44，140.78，140.42，134.97，130.35，130.21，128.76，128.51，127.74，126.59，126.50，122.82，119.70，117.80，107.83，62.23，53.08，32.51，25.49.
methyl-4- (5- (4-chlorophenyl) -4-oxo-1- (p-tolyl) -2, 3, 4, 5, 6, 7-hexahydro-1-hydro-6-pyrrolo [3,2-c ]]Pyridyl) benzoate white solid, yield: 56%, melting point: 175-177 ℃;1H NMR(400MHz，CDCl3)δ7.96(d，J＝8.0Hz，2H)，7.31(d，J＝8.0Hz，2H)，7.18(d，J＝8.8Hz，2H)，7.10(d，J＝8.0Hz，4H)，6.76(d，J＝8.0Hz，2H)，5.18(s，1H)，3.99-3.91(m，2H)，3.89(s，3H)，3.40(dd，J＝16.0，5.2Hz，1H)，3.04(t，J＝10.4Hz，1H)，2.97-2.93(m，1H)，2.83(d，J＝15.6Hz，1H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ166.49，165.51，145.62，140.59，138.13，134.09，130.50，130.00，129.92，129.70，128.58，126.62，126.54，121.13，62.04，54.01，52.13，31.95，25.44，20.72.
5- (4-chlorophenyl) -1- (2-methoxyphenyl) -6-phenyl l-1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 52%, melting point: 147 ℃ and 149 ℃;1H NMR(400MHz，CDCl3)δ7.29-7.26(m，1H)，7.22(t，J＝3.8Hz，4H)，7.16-7.11(m，3H)，7.08-7.06(m，2H)，6.82(t，J＝8.0Hz，3H)，5.00(dd，J＝6.4，2.8Hz，1H)，3.92-3.86(m，1H)，3.74-3.69(m，1H)，3.50(s，3H)，3.04-2.86(m，3H)，2.46(d，J＝16.4Hz，1H).13C NMR(100MHz，CDCl3)δ165.84，154.93，140.98，130.27，129.27，128.63，128.43，128.21，127.55，126.80，126.59，120.86，111.86，99.94，62.28，55.24，31.47，25.88.
5- (4-chlorophenyl) -1- (3-methoxyphenyl) -6-phenyl-1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 58%, melting point: 138 ℃ to 140 ℃;1H NMR(400MHz，CDCl3)δ7.30(d，J＝5.6Hz，2H)，7.30-7.28(m，3H)，7.23(d，J＝8.4Hz，3H)，7.17(d，J＝8.8Hz，2H)，6.64(dd，J＝8.4，2.0Hz，1H)，6.50(d，J＝8.0Hz，1H)，6.43(s，1H)，5.19-5.17(m，1H)，4.07-3.94(m，2H)，3.81(s，3H)，3.55-3.46(m，1H)，3.11-3.05(m，1H)，3.00-2.97(m，2H).13C NMR(100MHz，CDCl3)δ165.62，160.32，152.92，142.39，140.93，140.61，130.19，130.00，128.70，128.46，127.64，126.56，112.69，108.10，106.56，62.26，55.28，53.33，32.53，25.46.
5- (4-chlorophenyl) -1- (4-methoxyphenyl) -6-phenyl-1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 62%, melting point: 134-137 ℃;1H NMR(400MHz，CDCl3)δ7.30-7.27(m，3H)，7.24-7.22(m，2H)，7.18(d，J＝8.8Hz，2H)，7.11(d，J＝8.8Hz，2H)，6.84-6.73(m，4H)，5.11(dd，J＝6.0，3.2Hz，1H)，3.92(t，J＝9.6Hz，2H)，3.78(s，3H)，3.29(dd，J＝16.8，6.4Hz，1H)，3.09-3.01(m，1H)，2.97-2.89(m，1H)，2.76(d，J＝14.4Hz，1H).13C NMR(100MHz，CDCl3)δ165.80，156.71，141.00，140.61，134.21，130.21，128.74，128.50，127.69，126.64，126.57，123.40，114.60，62.21，55.55，54.75，32.11，25.57.
6- (2-chlorophenyl) -5- (4-chlorophenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 57%, melting point: 140 ℃ and 141 ℃;1H NMR(400MHz，CDCl3)δ7.45-7.43(m，1H)，7.33(dd，J＝4.8，2.0Hz，1H)，7.24-7.21(m，2H)，7.19(d，J＝8.4Hz，2H)，7.10-7.08(m，4H)，6.75(d，J＝8.0Hz，2H)，5.52(d，J＝4.8Hz，1H)，4.03-3.90(m，2H)，3.38(dd，J＝16.4，6.0Hz，1H)，3.08-2.89(m，3H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ165.85，140.87，138.60，137.61，133.33，131.72，130.23，130.14，129.87，129.05，128.65，128.51，127.08，126.28，120.52，59.28，53.61，29.83，25.43，20.69.
6- (3-chlorophenyl) -5- (4-chlorophenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 55%, melting point: 174 ℃ and 177 ℃;1H NMR(400MHz，CDCl3)δ7.45-7.43(m，1H)，7.34-7.32(m，1H)，7.23-7.21(m，2H)，7.19(d，J＝8.8Hz，2H)，7.11-7.07(m，4H)，6.75(d，J＝8，4Hz，2H)，5.52(dd，J＝6.8，2.4Hz，1H)，4.04-3.88(m，2H)，3.38(dd，J＝17.2，7.2Hz，1H)，3.10-2.97(m，2H)，2.92(dd，J＝10.0，2.4Hz，1H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ165.85，140.92，138.60，137.63，133.24，131.71，130.14，129.86，129.05，128.64，128.50，127.08，126.25，120.45，105.13，59.27，53.53，29.82，25.42，20.69.
5, 6-bis (4-chlorophenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 61%, melting point: 151-152 ℃;1H NMR(400MHz，CDCl3)δ7.26-7.24(m，2H)，7.18(t，J＝7.6Hz，4H)，7.11(dd，J＝7.6，3.6Hz，4H)，6.78(d，J＝8.4Hz，2H)，5.11-5.10(m，1H)，4.04-3.88(m，2H)，3.38(dd，J＝16.8，6.4Hz，1H)，3.03(t，J＝11.6Hz，1H)，2.96-2.92(m，1H)，2.79(d，J＝16.4Hz，1H)，2.31(s，3H).13C NMR(100MHz，CDCl3)δ165.48，140.65，139.02，138.18，133.43，130.34，129.88，128.86，128.52，127.89，126.47，120.93，61.59，53.82，32.10，25.40，20.71.
5- (4-chlorophenyl) -1, 6-di-p-methylphenyl-1, 2, 3, 5, 6, 7-hexahydro-4 hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 58%, melting point: 147 ℃ and 149 ℃;1H NMR(400MHz，CDCl3)δ7.45-7.43(m，1H)，7.33(dd，J＝6.4，4.8Hz，1H)，7.23-7.17(m，4H)，7.10-7.08(m，4H)，6.74(d，J＝8.4Hz，2H)，5.52(dd，J＝6.8，2.4Hz，1H)，4.02-3.87(m，2H)，3.40-3.34(m，1H)，3.30-2.89(m，3H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ165.74，140.68，138.16，137.44，137.14，133.87，130.34，129.86，129.37，128.45，126.68，126.40，120.92，62.03，54.00，32.35，25.44，21.00，20.73.
5- (4-chlorophenyl) -6- (m-methylphenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 55%, melting point: 160 ℃ and 161 ℃;1H NMR(400MHz，CDCl3)δ7.18-7.15(m，3H)，7.14-7.09(m，4H)，7.06-7.01(m，3H)，6.78(d，J＝8.0Hz，2H)，5.10(dd，J＝6.0，2.8Hz，1H)，4.03-3.88(m，2H)，3.39(dd，J＝16.4，6.0Hz，1H)，3.04(t，J＝10.6Hz，1H)，3.98-2.89(m，1H)，2.87(d，J＝15.2Hz，1H)，2.30(d，J＝2.8Hz，6H).13C NMR(100MHz，CDCl3)δ165.69，140.89， 140.41，138.34，130.06，129.79，128.50，128.37，127.10，126.51，123.57，120.74，62.12，53.77，32.30，25.42，21.48，20.69.
5- (4-chlorophenyl) -6- (o-methylphenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 63%, melting point: 164-165 ℃;1H NMR(400MHz，CDCl3)δ7.18-7.15(m，3H)，7.14-7.09(m，4H)，7.06-7.01(m，3H)，6.78(d，J＝8.4Hz，2H)，5.10(dd，J＝6.0，3.2Hz，1H)，4.05-3.88(m，2H)，3.38(dd，J＝16.8，6.4Hz，1H)，3.06-2.93(m，2H)，2.86(d，J＝17.2Hz，1H)，2.30(d，J＝2.4Hz，6H).13C NMR(100MHz，CDCl3)δ165.69，140.91，140.44，138.34，130.06，129.80，128.50，128.38，127.10，126.52，123.57，120.75，62.12，53.7832.30，25.42，21.48，20.69.
5- (4-chlorophenyl) -6- (4-methoxyphenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 43%, melting point: 154-156 ℃;1H NMR(400MHz，CDCl3)δ7.17(t，J＝64Hz，3H)，7.13-7.08(m，5H)，6.81-6.75(m，4H)，5.07(dd，J＝6.0，3.2Hz，1H)，4.01-3.87(m，2H)，3.77(s，3H)，3.33(dd，J＝16.8，6.4Hz，1H)，3.04-2.87(m，2H)，2.82(dd，J＝16.8，2.4Hz，1H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ165.73，158.87，153.65，141.12，138.73，133.25，132.63，129.97，129.80，128.38，127.70，126.62，120.67，113.94，99.95，61.71，55.20，53.58，32.48，25.48，20.70.
5- (4-chlorophenyl) -6- (3-methoxyphenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 51%, melting point: 160-162 ℃;1H NMR(400MHz，CDCl3)δ7.17(d，J＝8.8Hz，2H)，7.14(s，2H)，7.11-7.07(m，6H)，6.77(d，J＝8.0Hz，2H)，5.10(dd，J＝6.0，3.2Hz，1H)，4.02-3.88(m，2H)，3.36(dd，J＝16.8，6.4Hz，1H)，3.05-2.92(m，2H)，2.85(d，J＝16.4Hz，1H)，2.31(s，6H).13C NMR(100MHz，CDCl3)δ165.71，140.95，138.45，137.46，137.29，133.46，130.02，129.79， 129.31，128.36，126.55，126.39，120.71，99.90，61.95，53.69，32.35，25.42，20.97，20.68.(three carbons are not obserVed).HRMS(ESI)，m/zcalcd.for C27H25ClN2O2([M+H]+)467.1497，found：467.1490.
5- (4-chlorophenyl) -6- (2-methoxyphenyl) -1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 64%, melting point: 183-186 ℃;1H NMR(400MHz，CDCl3)δ7.30(d，J＝7.6Hz，1H)，7.24-7.22(m，1H)，7.20-7.11(m，4H)，7.09(d，J＝8.4Hz，2H)，6.91(t，J＝7.5Hz，1H)，6.84(d，J＝8.2Hz，1H)，6.74(d，J＝8.4Hz，2H)，5.47(dd，J＝6.8，2.0Hz，1H)，4.02-3.85(m，2H)，3.77(s，3H)，3.31(dd，J＝16.8，6.8Hz，1H)，3.08-2.89(m，3H)，2.30(s，3H).13C NMR(100MHz，CDCl3)δ166.11，155.68，141.10，129.87，129.72，128.73，128.31，127.84，126.31，120.49，120.38，110.49，57.04，55.25，53.61，29.89，25.38，20.69.
5- (4-chlorophenyl) -6-cyclohexyl-1- (p-methylphenyl) -1, 2, 3, 5, 6, 7-hexahydro-4-hydro-pyrrolo [3,2-c ] pyridin-4-one
White solid, yield: 25%, melting point: 153-156 ℃;1H NMR(400MHz，CDCl3)δ7.30(s，4H)，7.17(d，J＝8.0Hz，2H)，6.92(d，J＝8.0Hz，2H)，4.12(dd，J＝20.4，10.0Hz，1H)，3.92-3.86(m，2H)，3.01-2.87(m，3H)，2.67(d，J＝17.2Hz，1H)，2.34(s，3H)，1.65(s，4H)，1.59-1.53(m，2H)，1.14-0.94(m，4H).13C NMR(100MHz，CDCl3)δ165.22，141.19，138.50，130.97，129.98，129.38，129.11，128.72，128.67，120.98，64.04，54.10，41.06，30.30，29.18，26.10，26.04，25.50，20.79。
Claims (1)
1. a method for synthesizing 4 hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds comprises the steps of taking pyrrole compounds and aldehyde as raw materials, taking PEG-400 as a raw material, taking ammonium acetate as a catalyst, preparing the 4 hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compounds in one step under the heating condition,
wherein:
the reactant is pyrrole compound and aldehyde compound;
substituent R1Selected from 4-methylphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl;
substituent R2Selected from 2-chlorophenyl, 3-chlorophenyl, 4-carbethoxyphenyl, 4-methylphenyl, 2-methoxyphenyl;
substituent R3Selected from 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, cyclohexyl;
the catalyst is ammonium acetate, and the using amount of the ammonium acetate catalyst is 10 times of that of the pyrrole compound;
the reaction solvent is PEG-400;
the reaction is carried out under heating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510195454.3A CN104829614B (en) | 2015-04-17 | 2015-04-17 | Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510195454.3A CN104829614B (en) | 2015-04-17 | 2015-04-17 | Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104829614A CN104829614A (en) | 2015-08-12 |
| CN104829614B true CN104829614B (en) | 2020-04-28 |
Family
ID=53807853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510195454.3A Expired - Fee Related CN104829614B (en) | 2015-04-17 | 2015-04-17 | Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104829614B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009055828A1 (en) * | 2007-10-25 | 2009-04-30 | Medivation Technologies, Inc. | New tetracyclic compounds |
-
2015
- 2015-04-17 CN CN201510195454.3A patent/CN104829614B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009055828A1 (en) * | 2007-10-25 | 2009-04-30 | Medivation Technologies, Inc. | New tetracyclic compounds |
Non-Patent Citations (2)
| Title |
|---|
| First Cdc7 Kinase Inhibitors: Pyrrolopyridinones as Potent and Orally Active Antitumor Agents. 2. Lead Discovery;Maria Menichincheri et al.;《J. Med. Chem.》;20081230;第52卷;293-307 * |
| Lianqiang Zhang et al..Iron-Catalyzed Vinylogous Aldol Condensation of Biginelli Products and Its Application toward Pyrido[4,3‑d]pyrimidinones.《J. Org. Chem.》.2014,第79卷2281-2288. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104829614A (en) | 2015-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Safari et al. | Ultrasound-promoted an efficient method for one-pot synthesis of 2-amino-4, 6-diphenylnicotinonitriles in water: a rapid procedure without catalyst | |
| Zhao et al. | One-pot synthesis and its practical application in pharmaceutical industry | |
| Rueping et al. | Asymmetric Proline‐Catalyzed Addition of Aldehydes to 3H‐Indol‐3‐ones: Enantioselective Synthesis of 2, 3‐Dihydro‐1H‐indol‐3‐ones with Quaternary Stereogenic Centers | |
| Yeh et al. | Exploring the scope of the isothiourea-mediated synthesis of dihydropyridinones | |
| Nandi et al. | First InCl3-catalyzed, three-component coupling of aldehydes, β-naphthol, and 6-amino-1, 3-dimethyluracil to functionalized naphthopyranopyrimidines | |
| Wang et al. | Enantioselective synthesis of chiral α, β-unsaturated γ-substituted butyrolactams by organocatalyzed direct asymmetric vinylogous Michael addition of α, β-unsaturated γ-butyrolactam to 2-enoylpyridines | |
| Pharande | Synthesis of lactams via isocyanide-based multicomponent reactions | |
| Xiao et al. | An unexpected multi-component reaction to synthesis of 3-(5-amino-3-methyl-1H-pyrazol-4-yl)-3-arylpropanoic acids in ionic liquid | |
| Mohammadpoor-Baltork et al. | Environmental-friendly synthesis of oxazolines, imidazolines and thiazolines catalyzed by tungstophosphoric acid | |
| Liu et al. | Synthesis of benzo-annulated 1, 3-oxazine derivatives through the multi-component reaction of arynes with N-heteroaromatics and aldehydes or ketones | |
| Huang et al. | The first asymmetric synthesis of a 4-aryl-substituted 5-carboxy-3, 4-dihydropyridin-2-one derivative | |
| Mullens et al. | Two approaches to the chemical development and large-scale preparation of a pyrimidyl tetrazole intermediate | |
| Bethel et al. | Optimized scale up of 3-pyrimidinylpyrazolo [1, 5-a] pyridine via Suzuki coupling; a general method of accessing a range of 3-(hetero) arylpyrazolo [1, 5-a] pyridines | |
| M Heravi et al. | Isocyanide-based cascade reactions in the synthesis of aza-heterocycles: A marriage of convenience | |
| CN104829614B (en) | Method for synthesizing 4-hydrogen-pyrrole [3,2-c ] pyridine-4-ketone compound | |
| Albaneze-Walker et al. | Practical application of new catalytic methods: a concise synthesis of a potent PDE IV inhibitor | |
| Gupton et al. | The application of vinylogous iminium salt derivatives to an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B | |
| Bhowmik et al. | A novel stereoselective one-pot synthesis of 2-susbstituted amino-5, 6-dihydro-4 H-1, 3-thiazines via primary allylamines afforded from Morita–Baylis–Hillman acetates | |
| Raimondi et al. | One-pot asymmetric cyclocarbohydroxylation sequence for the enantioselective synthesis of functionalised cyclopentanes | |
| Wei et al. | Construction of an isoquinolinone framework from carboxylic-ester-directed umpolung ring opening of methylenecyclopropanes | |
| CN109020860B (en) | 2-aryl-3-ester group polysubstituted pyrrole compound and synthesis and refining method thereof | |
| Moazami et al. | Synthesis of 2, 3-Dihydro-1, 3-oxazin-4-ones via a Mild Formal [4+ 2] Cycloaddition of Acylketenes with Aldimines | |
| Just-Baringo et al. | Highly efficient, multigram and enantiopure synthesis of (S)-2-(2, 4′-bithiazol-2-yl) pyrrolidine | |
| CN110117258B (en) | Preparation method of 2,4, 6-triaryl substituted pyrimidine compound | |
| KR102212344B1 (en) | Furan compounds bearing a pyrazole skeleton, their derivatives, and synthetic method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Zhiguo Inventor after: Huang Yuanyuan Inventor after: Ma Nana Inventor after: Zhang Guisheng Inventor after: Liu Qingfeng Inventor before: Zhang Zhiguo Inventor before: Ma Nana Inventor before: Zhang Guisheng Inventor before: Liu Qingfeng Inventor before: Huang Yuanyuan |
|
| COR | Change of bibliographic data | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200428 Termination date: 20210417 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |