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CN101066945B - A method for synthesizing 3-position substituted lactam compounds - Google Patents

A method for synthesizing 3-position substituted lactam compounds Download PDF

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CN101066945B
CN101066945B CN200710041247A CN200710041247A CN101066945B CN 101066945 B CN101066945 B CN 101066945B CN 200710041247 A CN200710041247 A CN 200710041247A CN 200710041247 A CN200710041247 A CN 200710041247A CN 101066945 B CN101066945 B CN 101066945B
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CN101066945A (en
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游书力
李公强
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

本发明提供了一种合成3-取代内酰胺化合物的方法，是一种有效的以氮杂环卡宾作为催化剂，由醛基取代的小环胺类化合物高效率的合成3-取代内酰胺化合物的方法。与现有方法相比，该方法可适底物范围广，催化剂方便易得，反应条件温和，操作简便，而且反应效率高。另外，当底物中存在手性季碳中心时，该反应可以将其手性传递到产物中，可用来合成高对应选择性的含季碳中心的内酰胺类化合物。而且该方法无需加入任何金属盐类化合物，从而有利于药物的生产和处理。The invention provides a method for synthesizing 3-substituted lactam compounds, which is an effective method for efficiently synthesizing 3-substituted lactam compounds from small ring amine compounds substituted by aldehyde groups by using nitrogen heterocyclic carbene as a catalyst method. Compared with the existing methods, the method has a wide range of suitable substrates, convenient and easy-to-obtain catalysts, mild reaction conditions, simple operation and high reaction efficiency. In addition, when there is a chiral quaternary carbon center in the substrate, the reaction can transfer its chirality to the product, which can be used to synthesize lactam compounds containing a quaternary carbon center with high enantioselectivity. Moreover, the method does not need to add any metal salt compound, which is beneficial to the production and treatment of medicines.

Description

A kind of method of synthetic 3-substituted lactan compound
Technical field
The present invention relates to a kind of method of synthetic 3-substituted lactan compound, relate in particular to a kind of method that keeps to come the spirocyclic lactams compound of synthesis of optically active by quaternary carbon chiral centre chirality in the substrate.This method is the reaction by the little cyclic amine compound ring expansion of the precursor salt of N-heterocyclic carbine and the on-the-spot N-heterocyclic carbine catalysis aldehyde radical replacement that generates of alkali effect, the reaction of the little cyclic amine compound ring expansion that also can be directly replaced by N-heterocyclic carbine catalysis aldehyde radical, this reaction can be synthesized the 3-substituted lactan compound efficiently.
Background technology
In recent years, organic molecule catalysis has caused extensive concern [(a) Seayad, the J. of academia and industry member in worldwide owing to advantages such as it are easily synthetic, and structural modification is convenient, and heavy metal free is residual; List, B.Org.Biomol.Chem.2005,3,719-724. (b) Dalko, P.I.; Moisan, L.Angew.Chem.Int.Ed.2004,43,5138-5175.], be that the organic reaction of catalyst has obtained development [a) H.Stetter, Angew.Chem.1976,88,695-704 rapidly especially in recent years wherein by N-heterocyclic carbine; Angew.Chem.Int.Ed.1976,15,639-647; B) M.S.Kerr, J.Read de Alaniz, T.Rovis, J.Am.Chem.Soc.2002,124,10298-10299; C) A.E.Mattson, A.R.Bharadwaj, K.A.Scheidt, J.Am.Chem.Soc.2004,126,2314-2315; D) M.S.Kerr, T.Rovis, J.Am.Chem.Soc.2004,126,8876-8877; E) J.Read de Alaniz, T.Rovis, J.Am.Chem.Soc.2005,127,6284-6289; F) Q.Liu, T.Rovis, J.Am.Chem.Soc.2006,128,2552-2553; G) Y.Hachisu, J.W.Bode, K.Suzuki, J.Am.Chem.Soc.2003,125,8432-8433; H) D.Enders, O.Niemeier, T.Balensiefer, Angew.Chem.2006,118,1491-1495; Angew.Chem.Int.Ed.2006,45,1463-1467; I) H.Takikawa, Y.Hachisu, J.W.Bode, K.Suzuki, Angew.Chem.2006,118,3572-3574; Angew.Chem.Int.Ed.2006,45,3492-3494; J) M.He, G.J.Uc, J.W.Bode, J.Am.Chem.Soc.2006,128,15088-15089; K) G.-Q.Li, L.-X.Dai, S.-L.You, Chem.Commun.2007,852-854], in this field, our latest developments the ring expansion of the little cyclic amine compound that replaces by N-heterocyclic carbine catalysis aldehyde radical, this reaction can be synthesized the 3-substituted lactan compound expeditiously, and this compounds is present in [a) N.C.Warshakoon in the natural of a large amount of biologically actives and the non-natural product; S.Wu; A.Boyer; R.Kawamoto; J.Sheville; S.Renock; K.Xu; M.Pokross; A.G.Evdokimov; R.Walter; M.Mekel.Bioorg.Med.Chem.Lett.2006,16,5598-5601; B) J.Uddin; K.Ueda; E.Siwu; M.Kita; D.Uemura Biorg.Med.Chem., 2006,14,6954-6961; C) H.Ishikawa; G.I.Elliott; J.Velcicky; Y.Choi; D.Boger J.Am.Chem.Soc., 2006,128,10596-10612; D) Hamlyn, Richard John; Rigoreau, Laurent Jean Martin; Raynham, Tony Michael; Priestley, Rachael Elizabeth; Soudy, Christelle Nicole Marguerite; Lyko, Frank; Bruckner, Bodo; Kern, Oliver Thomas.PCT Int.Appl.2007,71; E) Jacyno, John M.; Lin, Nan-Homg; Holladay, Mark W.; Sullivan, James P.CurrentTopics in Plant Physiology (1995), 15 (Phytochemicals and Health), 294-6.f) J.A.Ferrendelli; H.J.Kupferberg Advances in Neurology 1980,27,587-96.] the synthetic report of the lactam compound that the 3-position replaced in the document at present is a lot, but wherein all there are metal participation reaction or reaction conditions harsh mostly, shortcomings such as the reaction times is very long, thereby develop a kind of easy to operate, mild condition, and the method for the high synthetic 3-substituted lactan compound of efficient is the emphasis and the difficult point of this respect.Inventor development utilize aza ring carbene precursor salt and alkali effect, the scene generates N-heterocyclic carbine or directly uses this organic micromolecule catalyst of N-heterocyclic carbine, by aldehyde radical being replaced the synthetic of lactam compound that this substrate ring expansion that conveniently is easy to get of little cyclic lactam realizes that the 3-position replaces, the synthetic of this compounds had great significance.
Summary of the invention
The present invention seeks to provide a kind of method of synthetic 3-substituted lactan compound efficiently.When especially containing the quaternary carbon chiral centre in substrate, reaction can remain into chirality in the product, can be used to the 3-substituted lactan compound of the high enantioselectivity of high-level efficiency ground synthesis of optically active.
Method of the present invention is a kind of method that is replaced the synthetic 3-position of tetra-atomic ring aminated compounds substituted lactams compound efficiently by aldehyde radical.This method is to generate N-heterocyclic carbine as catalyzer by aza ring carbene precursor salt and alkali effect scene, also can directly use N-heterocyclic carbine as catalyzer.
Method of the present invention institute synthetic 3-position substituted lactams compound molecule general formula is:
Figure G2007100412478D00031
In the formula: R 1Or R 2Be selected from H arbitrarily, contain C 1-C 16Alkyl, amino, alkoxy or halogen atom etc.; R 3Be selected from the aryl or the C of various acyl groups, replacement arbitrarily 1-C 16Alkyl etc.; X be carbonyl or
Figure G2007100412478D00032
N=0,1 or 2;
The lactam compound that 3-of the present invention position replaces is that the little cyclic amine compound that replaces with aldehyde radical is a raw material, in the presence of organic solvent, the N-heterocyclic carbine catalyzed reaction that generates with the effect of aza ring carbene precursor salt and alkali makes, also can directly make, can be represented by the formula with the N-heterocyclic carbine catalyzed reaction:
Figure G2007100412478D00033
The structural formula of the little cyclic amine compound that aldehyde radical replaces is: R wherein 1Or R 2Be selected from H arbitrarily, contain C 1-C 16Alkyl, amino, alkoxyl group or halogen atom etc.; R 3Be selected from the aryl or the C of acyl group, replacement arbitrarily 1-C 16Alkyl etc.; X be carbonyl or
Figure G2007100412478D00035
N=0,1 or 2; When generating N-heterocyclic carbine as catalyzer with aza ring carbene precursor salt and alkali effect scene, the structural formula of the precursor salt of N-heterocyclic carbine can be the following structural formula of optically pure arbitrarily or its enantiomorph or raceme, but not limit by diagram:
Figure G2007100412478D00036
When directly using N-heterocyclic carbine as catalyzer, the structural formula of N-heterocyclic carbine can be the following structural formula of optically pure arbitrarily or its enantiomorph or raceme, but not limit by diagram:
Figure G2007100412478D00041
Wherein, R 4, R 5, R 6, R 7, R 8, R 9, R 10, R 11, R 12, R 13, R 14, R 15, R 16Or R 17Be H, C 1-C 16Alkyl, aryl, substituted aryl; Substituting group on the aryl of described replacement is the amido of alkyl, alkoxyl group or replacement, and above-mentioned each substituting group can become key separately or become key to form C each other 5-C 7Cycloalkyl, aryl, substituted aryl, the heteroaryl that contains N, O, S or Heterocyclylalkyl; A 1, A 2, A 3, A 4Be Cl -, Br -, BF 4 -Or ClO 4 -
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0] ninth of the ten Heavenly Stems-5-alkene, cesium carbonate, potassiumphosphate, two (trimethyl silicon based) sodium amide, two (trimethyl silicon based) Lithamide, two (trimethyl silicon based) potassium amide, potassium tert.-butoxide, sodium tert-butoxide or diisopropyl ethyl amine;
The mol ratio that described aldehyde radical replaces little cyclic amine compound, aza ring carbene precursor salt or N-heterocyclic carbine, alkali is 1: 0.01-0.2: 0-0.2.
When with aza ring carbene precursor salt and alkali effect, on-the-spotly generate N-heterocyclic carbine catalysis should reaction the time, little cyclic amine compound, aza ring carbene precursor salt and the alkali of described aldehyde radical replacement mol ratio 1: 0.01-0.2: 0.01-0.2.Recommending mol ratio is 1: 0.2: 0.2.Especially the mol ratio of recommendation response is: aldehyde radical replaces little cyclic amine compound: aza ring carbene precursor salt: alkali=1: 0.01: 0.01.
When directly with N-heterocyclic carbine catalysis should reaction the time, little cyclic amine compound, N-heterocyclic carbine and the alkali that described aldehyde radical replaces mol ratio 1: 0.01-0.2: 0.Especially the mol ratio of recommendation response is: aldehyde radical replaces little cyclic amine compound: N-heterocyclic carbine: alkali=1: 0.01: 0.
Temperature of reaction is recommended as 0 ℃ to 120 ℃, and further the recommendation response temperature is: 25 ℃ to 110 ℃.Reaction times was recommended as 5 hours-48 hours.
R wherein 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, R 11, R 12, R 13, R 14, R 15, R 16And R 17Ditto described.
The alkyl of being mentioned among the present invention,-oxyl, acyl group etc., unless otherwise indicated, all recommending carbon number is 1～18 group, and further to recommend carbon number be 1～10, and especially recommending carbon number is 1～5.The cycloalkyl of being mentioned among the present invention unless otherwise indicated, refers to that all carbon number is 3～18 group, further recommending carbon number is 3～10, and especially recommending carbon number is 3～7.The aryl of being mentioned among the present invention unless otherwise indicated, all refers to phenyl, C 5～C 10The heterocyclic radical that contains N, O or S, be recommended as phenyl.The heteroaryl of mentioning among the present invention is recommended C 5～C 10The heterocyclic radical that contains N, O and S.
In the inventive method, described organic solvent can be polarity or non-polar solvent.As benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, N,N-DIMETHYLACETAMIDE, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile etc.
Adopt the inventive method products therefrom can pass through recrystallization, thin-layer chromatography, methods such as column chromatography underpressure distillation are separated.As the method with recrystallization, recommending solvent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be methylene dichloride-normal hexane, Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane or Virahol-ethyl acetate-mixed solvents such as sherwood oil.With thin-layer chromatography and column chromatography method, used developping agent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane or Virahol-ethyl acetate-mixed solvents such as sherwood oil, its volume ratio can be respectively: polar solvent: non-polar solvent=1: 0.1-500.For example: ethyl acetate: sherwood oil=1: 0.1-50, Virahol: sherwood oil=1: 0.1-500.
The invention provides some new 3-position substituted lactams compounds R for example wherein 1Be H; R 2Be methyl or phenyl; R 3Be phenyl, p-methylphenyl, benzyl, alkyl.This compounds can be through the reaction of routine with R 3Remove and with reduction of amide for amino and go up amino protecting group such as carbobenzoxy-(Cbz), use thereby have widely.
The invention provides a kind of effectively by aza ring carbene precursor salt and alkali effect, the on-the-spot N-heterocyclic carbine that generates or directly use N-heterocyclic carbine as catalyzer, the method for the high efficiency synthetic 3-of the little cyclic amine compound position substituted lactams compound that replaces by aldehyde radical.Compare with existing method, this method replaces little cyclic amine compound applicable to the aldehyde radical of number of different types, and the reaction conditions gentleness is easy and simple to handle.In addition, need not in the reaction to add any metal salt compound, thereby help medicine production and processing.And the productive rate of reaction is also better, is generally 78%-99%.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: the preparation of thiazoles aza ring carbene precursor salt
Under the room temperature argon shield; in an exsiccant reaction tubes with 4; 5-dimethylthiazole or 4-methyl-5-hydroxy ethylthiazole (1.0mmol) is dissolved in the 10mL exsiccant acetonitrile; under quick stirring condition; the cylite or the benzyl chlorine of (1.0mmol) are added drop-wise in the system slowly, refluxed 3 hours.Question response finishes, and naturally cools to room temperature, under stirring fast, slowly drips ethyl acetate 30mL in system, and system has a large amount of white solids to separate out, and leaves standstill.Filter, get white solid, be the precursor salt of thiazoles Cabbeen.
C1: bromination (3-benzyl-4,5-dimethylthiazole)
3-Benzyl-4，5-dimethylthiazolium?bromide
Figure G2007100412478D00061
Solid, 91% productive rate.′H?NMR(300MHZ，DMSO)67.492-7.324(m，5H)，5.809(s，2H)，2.499(s，3H)，2.327(s，3H)；MS(CI)m/z(relative?intensity)204(M，13.6)，171(8)，142(10.4)，114(72.81)，91(100).
C2: bromination [3-benzyl-4-methyl-5-(beta-hydroxy ethyl) thiazole]
3-Benzyl-5-(β-ethoxyethyl)-4-methy?thiazolium?Bromide
Figure G2007100412478D00062
White solid, 82% productive rate; ' H NMR (300MHz, CDCl 3) 11.51 (s, 1H), 7.35 (m, 5H), 6.12 (d, 2H, J=5.2Hz), 3.49-3.65 (m, 4H), 3.0l (t, 2H, J=5.4Hz), 2.42 (s, 3H), 1.19 (t, 3H, J=7.0Hz).
C3：2-Phenyl-6，7-dihydro-5H-pyrrolo[2，1-c][1，2，4]triazol-2-ium?chloride
Figure G2007100412478D00063
Overall yield C3 (15.778g 62%) .Rf (acetone)=0.09; 1H NMR (300MHz, D2O) δ 7.61-7.79 (m, 2H), 7.50-7.59 (m, 3H), 4.38 (dd, 2H, J=7.3,7.3Hz), 3.13 (dd, 2H, J=7.3,7.3Hz), 2.77 (ddd, 2H, J=15.0,7.7,7.7Hz); 13C NMR (100MHz, D2O) δ 163.9,135.5, and 131.0,130.3,121.3,47.5,26.7,21.5; IR (NaCl, compressing tablet) 1586,1513,1426,1382,967cm-1; M.p.180-184 ℃; HRMS (fast atom bombardment(FAB)), C 11H 12N 3, calculated value 186.1031. measured value 186.1038.
C4：1，3，4-triphenyl-4H-1，2，4-triazol-1-ium?perchlorate
Figure G2007100412478D00071
MS(m/z，rel.intensity)397(M +，100)，398(22)，399(32)
C5:1,3-two (2, the 6-diisopropyl phenyl) imidazole hydrochloride
1，3-Bis(2，6-diisopropylphenyl)imidzaolium?chloride
Figure G2007100412478D00072
MS(m/z，rel.intensity)397(M +，100)，398(22)，399(32).
C6:1,3-two (mesitylene base) imidazole hydrochloride
1，3-Bis(2，4，6-trimethylphenyl)imidazolium?chicride
Figure G2007100412478D00073
MS (m/z, relative intensity) 340 (M +, 100), 341 (23), 342 (32).
C7：
2-phenyl-6，10b-dihydro-4H，5aH-5-oxa-3，10cdiaza-2-azoniacyclopenta[c]fluor--ene?tetrafluoroborate
Figure G2007100412478D00081
Racemization or chipal compounds
MS (m/z, relative intensity) 337 (M +, 100), 336 (24), 338 (20).
C8：
2-Pentafluorophenyl-6，10b-dihydro-4H，5aH-5-oxa-3，10cdiaza-2-azoniacyclopenta[c]fluorene?tetrafluoroborate
Figure G2007100412478D00082
Raceme or chipal compounds
MS (m/z, relative intensity) 380 (M +, 100), 381 (20), 382 (2).
C9：2-(2，4，6-trimethylphenyl)-6，10b-dihydro-4H，5aH-5-oxa-3，10cdiaza--2-azoniacyclopenta[c]fluorene?tetrafluoroborate
Figure G2007100412478D00083
Raceme or chipal compounds
MS (m/z, relative intensity) 419 (M +, 100), 418 (25), 420 (24).
Embodiment 2: the ring expansion of N-heterocyclic carbine catalysis aldehyde radical substituted lactams compound
Figure G2007100412478D00084
Under argon shield, in an exsiccant reaction tubes, add aza ring carbene precursor salt compound (0.01mmol) successively, alkali (0.01mmol), aldehyde radical replace little cyclic amine compound (1.00mmol), and methylene dichloride 4.0mL refluxes.Reaction finishes, and removal of solvent under reduced pressure gets product with the residue column chromatography for separation.Do not add special instruction, reaction all is solvent with the methylene dichloride, and temperature of reaction refluxes.
P1:N-(p-methoxyphenyl)-3-phenyl succinimide
N-(4-methoxyphenyl)-3-phenylpyrrolidine-2，5-dione
Figure G2007100412478D00091
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/4, v/v; White solid, 99% productive rate; 1HNMR (CDCl 3, 300MHz) δ 2.97 (dd, 1H, J 1=4.8Hz, J 2=18.3Hz), 3.35 (dd, 1H, J 1=9.9Hz, J 2=18.6Hz), 3.82 (s, 3H), 4.16 (dd, 1H, J 1=4.8Hz, J 2=9.9Hz), 6.98 (d, 2H, J=9.0Hz), 7.23 (d, 2H, J=9.0Hz), 7.29-7.42 (m, 5H); 13C NMR (75MHz, CDCl 3): δ 37.2,45.9, and 55.4,114.5,124.4,127.3,127.6,128.0,129.2,137.2,159.5,175.4,176.9; IR (film): v Max(cm -1)=3007,2953,2834,1705,1513,1250,1198,777,703,670; MS (electron-bombardment, relative intensity) 293 (M +, 50), 161 (100); Ultimate analysis C 17H 15NO 3: calculated value: C, 72.58; H, 5.37; N, 4.98; Measured value: C, 72.42; H, 5.26; N, 4.83; M.p.161-162 ℃.
P2:N-(p-methoxyphenyl)-3-(p-methoxyphenyl) succinimide
N-(4-methoxyphenyl)-3-4-(methoxyphenyl)pyrrolidine-2，5-dione
Figure G2007100412478D00092
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/3, v/v; White solid, 98% productive rate; 1HNMR (CDCl 3, 300MHz) δ 2.94 (dd, 1H, J 1=4.8Hz, J 2=18.3Hz), 3.34 (dd, 1H, J 1=9.6Hz, J 2=18.6Hz), 3.81 (s, 3H), 3.82 (s, 3H), 4.12 (dd, 1H, J 1=4.8Hz, J 2=9.6Hz), 6.92 (d, 2H, J=8.7Hz), 6.98 (d, 2H, J=9.0Hz) 7.21-7.26 (m, 4H); 13CNMR (75MHz, CDCl 3): δ 37.2,45.1, and 55.3,55.4,114.4,114.6,124.4,127.6,128.4,129.1,159.2,159.5,175.5,177.2; IR (film): v Max(cm -1)=2960,2839,1705,1516,1251,1200,1181,1033,833,670; MS (electron-bombardment, relative intensity) 311 (M +, 43), 134 (100); Ultimate analysis C 18H 17NO 4: calculated value: C, 69.44; H, 5.50; N, 4.50; Measured value: C, 69.30; H, 5.79; N, 4.32; M.p.172-173 ℃.
P3:N-(p-methoxyphenyl)-3-(rubigan) succinimide
3-(4-chlorophenyl)-N-(4-methoxyphenyl)pyrrolidine-2，5-dione
Figure G2007100412478D00101
Catalyzer is C6 (1mol%); Reaction solvent is 1, and the 4-dioxane refluxes; Ethyl acetate/petroleum ether=1/4, v/v; White solid, 93% productive rate; 1HNMR (CDCl 3, 300MHz) δ 2.95 (dd, 1H, J 1=5.1Hz, J 2=18.6Hz), 3.37 (dd, 1H, J 1=9.6Hz, J 2=18.3Hz), 3.83 (s, 3H), 4.17 (dd, 1H, J 1=4.8Hz, J 2=9.6Hz), 6.99 (d, 2H, J=9.0Hz), 7.21-7.27 (m, 4H), 7.38 (d, 2H, J=8.4Hz); 13C NMR (75MHz, CDCl 3): δ 36.9,45.2, and 55.5,114.5,124.3,127.6,128.8,129.4,134.0,135.4,159.6,175.0,176.4; IR (compressing tablet): v Max(cm -1)=3472,3072,3012,2837,1783,1706,1513,1251,1205,1167,1029,832,670; MS (electron-bombardment, m/z, relative intensity) 315 (M +, 37), 149 (100); Ultimate analysis C 17H 14ClNO 3: calculated value: C, 64.67; H, 4.47; N, 4.44; Measured value: C, 64.63; H, 4.66; N, 4.39; M.p.197-198 ℃.
P4:N-(p-methoxyphenyl)-3-(2-thienyl) succinimide
N-(4-methoxyphenyl)-3-(thiophen-2-yl)pyrrolidine-2，5-dione
Figure G2007100412478D00102
Catalyzer is C6 (1mol%); Reaction solvent is 1, the 4-dioxane; Ethyl acetate/petroleum ether=1/4, v/v; White solid, 85% productive rate; 1H NMR (CDCl 3, 300MHz) δ 3.06 (dd, 1H, J 1=5.4Hz, J 2=18.3Hz), 3.37 (dd, 1H, J 1=9.6Hz, J 2=18.6Hz), 3.80 (s, 3H), 4.39 (dd, 1H, J 1=5.4Hz, J 2=9.6Hz), and 6.94-7.06 (m, 4H), 7.17-7.29 (m, 3H); 13C NMR (75MHz, CDCl 3): δ 37.1,41.0, and 55.4,114.4,124.2,125.3,125.5,127.1,127.5,138.3,159.5,174.5,175.5; IR (compressing tablet): v Max(cm -1)=3105,3004,2833,1902,1779,1709,1704,1516,1405,1250,1199,1175,1030,667; MS (electron-bombardment, m/z, relative intensity) 287 (M +, 3), 110 (100); HRMS (electron-bombardment) C 15H 13NO 3S (M +): calculated value 287.0616 measured values: 287.0619; M.p.122-124 ℃.
P5:N-(p-methoxyphenyl)-3-methyl succinimide
N-(4-methoxyphenyl)-3-methylpyrrolidine-2，5-dione
Figure G2007100412478D00111
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/5, v/v; White solid, 91% productive rate; 1HNMR (CDCl 3, 300MHz) δ 1.45 (d, 3H, J=7.2Hz), 2.49 (dd, 1H, J 1=3.6Hz, J 2=16.8Hz), 3.00-3.13 (m, 2H), 3.82 (s, 3H), 6.98 (d, 2H, J=9.3Hz), 7.19 (d, 2H, J=8.7Hz); 13C NMR (75MHz, CDCl 3): δ 16.8,34.7, and 36.5,55.4,114.4,124.5,127.6,159.4,175.7,179.8; IR (compressing tablet): v Max(cm -1)=3005,2943,2846,1773,1704,1511,1396,1245,1182,1166,1031,836,668; MS (electron-bombardment, m/z, relative intensity) 219 (M +, 100); HRMS (electron-bombardment) C 12H 13NO 3(M +): calculated value: 219.0895; Measured value: 219.0900; M.p.91-93 ℃.
P6:N-(p-methoxyphenyl)-3-n-pentyl succinimide
N-(4-methoxyphenyl)-3-pentylpyrrolidine-2，5-dione
Figure G2007100412478D00112
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/5, v/v; White solid, 99% productive rate; 1HNMR (CDCl 3, 300MHz) δ 0.9l (brs, 3H), 1.33-1.44 (m, 6H), 1.55-1.68 (m, 1H), 1.93-2.04 (m, 1H), 2.53 (m, 1H), 2.88-3.03 (m, 2H), 3.81 (s, 3H), 6.97 (d, 2H, J=9.0Hz), 7.18 (d, 2H, J=9.0Hz); 13C NMR (75MHz, CDCl 3): δ 14.0,22.4, and 26.3,31.4,31.4,34.5,40.0,55.4,114.4,124.5,127.6,159.4,176.0,179.3; IR (thin film): v Max(cm -1)=3074,2957,2932,2856,1776,1706,1519,1394,1255,1174,1027,822,769; MS (EI, m/z, rel.intensity) 275 (M +, 53), 205 (100); HRMS (EI) C 16H 21NO 3(M +): calculated value 275.1521; Measured value: 275.1521; M.p.67-68 ℃.
P7:N-(p-methoxyphenyl)-3-sec.-propyl succinimide
3-isopropyl-N-(4-methoxyphenyl)pyrrolidine-2，5-dione
Figure G2007100412478D00121
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/5, v/v; White solid, 93% productive rate; 1HNMR (CDCl 3, 300MHz) δ 0.96 (d, 3H, J=6.9Hz), 1.04 (d, 3H, J=7.2Hz), 2.39 (m, 1H), 2.58 (dd, 1H, J 1=4.2Hz, J 2=18.3Hz), 2.82 (dd, 1H, J 1=9.3Hz, J 2=18.3Hz), 2.93 (m, 1H), 3.80 (s, 3H), 6.96 (d, 2H, J=8.7Hz), 7.15 (d, 2H, J=9.0Hz); 13C NMR (75MHz, CDCl 3): δ 17.1,19.8, and 29.0,30.3,45.5,55.3,114.3,124.4,127.6,159.3,176.1,178.6; IR (compressing tablet): v Max(cm -1)=2963,2935,1709,1513,1399,1255,1200,1035,831,771,672; MS (electron-bombardment, m/z, relative intensity) 247 (M +, 100); HRMS (electron-bombardment) C 14H 17NO 3(M +): calculated value: 247.1208; Measured value: 247.1208; M.p.112-114 ℃.
P8:N-(p-methoxyphenyl)-3,3-dimethyl succinimide
N-(4-methoxyphenyl)-3，3-dimethylpyrrolidine-2，5-dione
Figure G2007100412478D00122
Catalyzer is C6 (5mol%); Ethyl acetate/petroleum ether=1/5, v/v; White solid, 97% productive rate; 1HNMR (CDCl 3, 300MHz) δ 1.42 (s, 6H), 2.71 (s, 2H), 3.83 (s, 3H), 6.98 (d, 2H, J=9.0Hz), 7.20 (d, 2H, J=9.0Hz); 13C NMR (75MHz, CDCl 3): δ 25.7,25.7, and 40.0,43.7,55.4,114.4,124.6,127.6,159.4,175.1,182.4; IR (compressing tablet): v Max(cm -1)=2936,2843,1775,1710,1511,1397,1248,1148,1033,834,788; MS (electron-bombardment, m/z, relative intensity) 233 (M +, 87), 83 (100); HRMS (electron-bombardment) C 13H 15NO 3(M +): calculated value: 233.1052; Measured value: 233.1051;
P9:N-(p-methoxyphenyl)-3-ethyl-3-phenyl succinimide
3-ethyl-N-(4-methoxyphenyl)-3-phenylpyrrolidine-2，5-dione
Figure G2007100412478D00123
Catalyzer is C6 (5mol%); Reaction solvent is 1, and the 4-dioxane refluxes ethyl acetate/petroleum ether=1/5, v/v; White solid, 97% productive rate; 1H NMR (CDCl 3, 300MHz) δ 0.97 (t, 3H, J=7.2Hz), 2.17 (dq, 2H, J 1=5.1Hz, J 2=7.2Hz), 3.06 (AB, 1H, J AB=18.3Hz), 3.25 (AB, 1H, J BA=18.0Hz), 3.80 (s, 3H), 6.97 (d, 2H, J=8.7Hz), 7.19 (d, 2H, J=8.7Hz), 7.27-7.51 (m, 5H); 13C NMR (75MHz, CDCl 3): δ 9.0,32.7, and 41.1,52.1,55.4,114.4,124.4,126.1,127.5,127.7,128.8,140.6,159.4,174.9,179.3; IR (compressing tablet): v Max(cm -1)=3474,3059,2970,2939,1779,1712,1515,1388,1253,1033,823,736,701; MS (electron-bombardment, m/z, relative intensity) 309 (M +, 66), 149 (100); HRMS (electron-bombardment) C 19H 19NO 3(M +): calculated value: 309.1365; Measured value: 309.1371.
P10:N-(all trimethylammoniums)-3-phenyl succinimide
N-mesityl-3-phenylpyrrolidine-2，5-dione
Figure G2007100412478D00131
Catalyzer is C6 (5mol%); Ethyl acetate/petroleum ether=1/5, v/v; White solid, 78% productive rate; 1HNMR (300MHz, CDCl 3) δ 2.09 (s, 3H), 2.11 (s, 3H), 2.30 (s, 3H), 3.05 (dd, 1H, J 1=5.1Hz, J 2=18.6Hz), 3.43 (dd, 1H, J 1=9.9Hz, J 2=18.6Hz), 4.24 (dd, 1H, J 1=5.1Hz, J 2=9.9Hz), 6.97 (d, 2H, J=4.5Hz), 7.31-7.44 (m, 5H); 13C NMR (75MHz, CDCl 3) δ 17.6,17.8,21.0,37.2,46.2,127.3,127.4,127.9,129.1,129.3,129.3,135.1,135.2,137.0,139.3,175.1,176.4; IR (compressing tablet): v Max(cm -1)=3466,3028,2919,1773,1712,1488,1372,1184,863,785,667; MS (electron-bombardment, m/z, relative intensity) 293 (M +, 30), 161 (100); HRMS (electron-bombardment) C 19H 19NO 2(M +): calculated value: 293.1416 measured values: 293.1412; M.p.137-138 ℃.
P11：
Figure G2007100412478D00132
Catalyzer is C6 (1mol%); Ethyl acetate/petroleum ether=1/3, v/v; White foam shape solid, 92% productive rate 99.9%ee, [chiral column AD-H, hexane/isopropyl alcohol=70/30,1.0mlmin -1, λ=220nm, t (maximum retention time)=19.67 minute, t (minimum retention time)=15.12 minutes]; [α] D 20=-46.5 (c1.0, CHCl 3). 1H NMR and 13There is rotational isomer in C NMR demonstration system, and its amount of substance ratio is 2: 1.. 1H NMR (300MHz, CDCl 3) δ 1.90-2.18 (m, 2H), 2.78 (AB, 1H, J AB=17.7Hz), 3.12,3.27 (AB, 1H, J BA=18.0Hz), 3.60-3.71 (m, 2H), 3.77,3.79 (s, 3H), 5.06-5.18 (m, 2H), 6.62,6.96 (d, 2H, J=9.0Hz), 6.79,7.26 (d, 2H, J=9.0Hz), 7.24-7.34 (m, 5H); 13C NMR (75Hz, CDCl 3) δ: 23.1,23.9,38.2,40.0,41.4,42.4,47.4,48.3,55.3,55.3,64.2,65.1,67.2,68.1,114.1,114.3,123.9,124.5,127.3,127.8,127.8,128.0,128.4,128.5,128.6,128.7,135.1,135.9,153.0,154.1,159.2,159.4,173.1,173.6,177.4,177.7; IR (compressing tablet): v Max(cm -1)=2957,2883,2840,1718,1696,1514,1417,1253,1213,1166; MS (electron-bombardment, m/z, relative intensity) 394 (M +, 27), 91 (100); HRMS (electron-bombardment) calculated value: C 22H 22N 2O 5(M +): 394.1529 measured values: 394.1535; M.p.107-108 ℃.
P12:N-(p-methoxyphenyl)-4-Phenylpyrrolidine ketone
N-(4-methoxyphenyl)-4-phenylpyrrolidin-2-one
Figure G2007100412478D00141
MS (m/z, relative intensity) 267 (M +, 100), 268 (19), 269 (2).
P13:N-(p-methoxyphenyl)-4-methyl-2-pyrrolidone
N-(4-methoxyphenyl)-4-methylpyrrolidin-2-one
Figure G2007100412478D00142
MS (m/z, relative intensity) 205 (M +, 100), 206 (13)
P14:N-(p-methoxyphenyl)-4-n-pentyl pyrrolidone
N-(4-methoxyphenyl)-4-penthylpyrrolidin-2-one
Figure G2007100412478D00151
MS (m/z, relative intensity) 261 (M +, 100), 262 (18), 263 (2).
Embodiment 3: the reduction of acid amides (application example) in the product
Figure G2007100412478D00152
Under argon shield, (0.5mmol is 182.0mg) with tetrahydrofuran (THF) 5mL to add P11 in dry system.After placing ice-water bath to be cooled to 0 ℃ the system, in system, slowly add LiAlH in batches 4(2.5mmol 101.3mg), stirred 30 minutes, removed ice-water bath, recovered room temperature naturally, stirred.The reaction back (TLC follows the tracks of reaction) that finishes, system is cooled to 0 ℃ after, slowly drip distilled water 0.18mL, stir after 30 minutes filtration.Wash solid with ethyl acetate, merge organic phase, dry back column chromatography.Petrol ether/ethyl acetate=3/1,3 ‰ triethylamine), get corresponding reduzate, productive rate 86%.
White solid.99.7%ee, [chiral column OD-H (15cm), hexane/isopropyl alcohol=98/2,0.7mlmin -1, λ=230nm, t (maximum retention time)=15.71 minute, t (minimum retention time)=13.29 minutes]; [α] D 20=-18.4 (c 0.82, CHCl 3). 1H NMR (300MHz, CDCl 3) δ 1.68-1.94 (m, 5H), 2.13-2.20 (m, 1H), 2.37 (s, 3H), 2.76-2.83 (m, 2H), 2.97 (d, 1H, J=9.3Hz), 3.21-3.29 (m, 1H), 3.35-3.44 (m, 2H), 3.76 (s, 3H), 6.52 (d, 2H, J=9.0Hz), 6.85 (d, 2H, J=9.6Hz); 13C NMR (75MHz, CDCl 3) 820.8,30.2,34.8,38.3,47.3,53.4,54.4,55.9,69.6,112.3,114.9,142.9,150.8; IR (compressing tablet): v Max(cm -1)=2979,2951,2828,2781,1516,1241,1042,814; MS (electron-bombardment, m/z, relative intensity) 246 (M +, 42), 150 (100) .HRMS (electron-bombardment) C 15H 22NO (M +): calculated value: 246.1732 measured values: 246.1736; M.p.46-48 ℃.

Claims (5)

1. the method for a synthetic 3-substituted lactan compound, it is characterized in that in the presence of organic solvent and 0 ℃～120 ℃ under, replacing little cyclic amine compound with aldehyde radical is raw material, the N-heterocyclic carbine that generates with aza ring carbene precursor salt and cesium carbonate, potassiumphosphate or alkali effect react the lactam compound that made the replacement of 3-position in 2-36 hour as catalyzer;
The mol ratio that described aldehyde radical replaces little cyclic amine compound, aza ring carbene precursor salt and cesium carbonate, potassiumphosphate or alkali is 1: 0.01-0.2: 0.01-0.2;
The structural formula that described aldehyde radical replaces little cyclic amine compound is
Figure F2007100412478C00011
Described aza ring carbene precursor salt has following structural formula:
Figure F2007100412478C00012
Described N-heterocyclic carbine has following structural formula:
Figure F2007100412478C00013
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0] ninth of the ten Heavenly Stems-5-alkene, two (trimethyl silicon based) sodium amide, two (trimethyl silicon based) Lithamide, two (trimethyl silicon based) potassium amide, potassium tert.-butoxide, sodium tert-butoxide or diisopropyl ethyl amine;
R wherein 1, R 2Be selected from H, C arbitrarily 1-C 16Alkyl, C 3-C 16Cycloalkyl, amino or amido, alkoxyl group or the halogen atom that replaces; R 3Be selected from the aryl or the C of acyl group, replacement arbitrarily 1-C 16Alkyl;
X be carbonyl or
Figure F2007100412478C00014
N=0 or 1;
R 4, R 5, R 6, R 7, R 8, R 9, R 10, R 11, R 12, R 13, R 14, R 15, R 16Or R 17Be H, C 1-C 16The aryl of alkyl, aryl or replacement;
Substituting group on the aryl of described replacement is alkyl, alkoxyl group; Substituting group on the amido of described replacement is C 1-C 16Alkyl, aryl or C 5～C 10The Heterocyclylalkyl that contains N, O, S; A 1, A 2, A 3Or A 4Be Cl arbitrarily -, Br -, BF 4 -Or ClO 4 -The carbon number of described alkyl, alkoxyl group or acyl group is 1～18; Described aryl is phenyl, C 5～C 10The heterocyclic radical that contains N, O or S.
2. the method for synthetic 3-substituted lactan compound according to claim 1 is characterized in that described 3-substituted lactan compound is an optical purity, and its structure is Wherein * is a chiral carbon atom, R 1, R 2, R 3With X according to claim 1.
3. the method for synthetic 3-substituted lactan compound according to claim 1 is characterized in that described 3-substituted lactan compound is a raceme, and its structure is
Figure F2007100412478C00022
R wherein 1, R 2, R 3With X according to claim 1.
4. the method for synthetic 3-substituted lactan compound as claimed in claim 1 is characterized in that described organic solvent is benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, N,N-DIMETHYLACETAMIDE, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
5. the method for synthetic 3-substituted lactan compound as claimed in claim 1 is characterized in that the 3-substituted lactan compound through recrystallization, thin-layer chromatography, and column chromatography or underpressure distillation are separated.
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Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2009293164B2 (en) 2008-09-18 2015-07-09 Northwestern University NMDA receptor modulators and uses thereof
EP2542254B1 (en) 2010-02-11 2018-09-26 Northwestern University Nmda receptor agonists and uses thereof
KR101692275B1 (en) 2010-02-11 2017-01-04 노오쓰웨스턴 유니버시티 Secondary structure stabilized nmda receptor modulators and uses thereof
CN102153557B (en) * 2011-01-21 2013-03-20 中国科学院上海有机化学研究所 Chiral center nitrogen heterocyclic carbine precursor salt with quadrol skeleton, synthetic method and application
SG11201505860XA (en) 2013-01-29 2015-08-28 Naurex Inc Spiro-lactam nmda receptor modulators and uses thereof
ES2618421T3 (en) 2013-01-29 2017-06-21 Aptinyx Inc. NMDA receptor spiro-lactam modulators and uses thereof
BR112015018095A2 (en) 2013-01-29 2017-07-18 Naurex Inc Spiro-lactam nmda receptor modulators and uses thereof
BR112015018089B1 (en) 2013-01-29 2022-09-20 Aptinyx Inc SPIRO-LACTAMA NMDA RECEPTOR MODULATING COMPOUNDS, PHARMACEUTICAL COMPOSITION COMPRISING THEM AND USE THEREOF
EA031905B1 (en) 2013-01-29 2019-03-29 Аптиникс Инк. Spiro-lactam nmda receptor modulators and use thereof
CA3024606C (en) 2016-05-19 2019-09-03 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
WO2017201285A1 (en) 2016-05-19 2017-11-23 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
EP3490990B1 (en) 2016-08-01 2023-12-06 Tenacia Biotechnology (Hong Kong) Co., Limited Spiro-lactam nmda modulators and methods of using same
ES2972533T3 (en) 2016-08-01 2024-06-13 Tenacia Biotechnology Hong Kong Co Ltd Spirolactam-based NMDA receptor modulators and their uses
EA201990424A1 (en) 2016-08-01 2019-08-30 Аптиникс Инк. SPIRALACTAM MODULERS OF NMDA RECEPTOR AND THEIR APPLICATION
WO2018026782A1 (en) 2016-08-01 2018-02-08 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
MX2019001322A (en) 2016-08-01 2019-09-11 Aptinyx Inc Spiro-lactam and bis-spiro-lactam nmda receptor modulators and uses thereof.
CN106916093B (en) * 2017-02-23 2019-07-09 福州大学 A kind of method that N-heterocyclic carbine catalyzes and synthesizes polysubstituted pyrrole alkane ketone compounds
KR102761196B1 (en) 2018-01-31 2025-02-03 테나시아 바이오테크놀로지 (홍콩) 코., 리미티드 Spiro-lactam NMDA receptor modulators and uses thereof
US12012413B2 (en) 2019-11-11 2024-06-18 Tenacia Biotechnology (Hong Kong) Co., Limited Methods of treating painful diabetic peripheral neuropathy

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Benito Alcaide, et al..Organocatalytic Ring Expansion of β-Lactams to γ-Lactams through a Novel N1-C4 Bond Cleavage. DirectSynthesis ofEnantiopure Succinimide Derivatives.Org. Lett.7 18.2005,7(18),3981-3984.
Benito Alcaide,et al..Organocatalytic Ring Expansion of β-Lactams to γ-Lactams through a Novel N1-C4 Bond Cleavage.DirectSynthesis ofEnantiopure Succinimide Derivatives.Org. Lett.7 18.2005,7(18),3981-3984. *
Ming He, et al..Catalytic Synthesis of γ-Lactams via Direct Annulations ofEnals and N-Sulfonylimines.Org. Lett.7 14.2005,7(14),3131-3134.
Ming He,et al..Catalytic Synthesis of γ-Lactams via Direct Annulations ofEnals and N-Sulfonylimines.Org. Lett.7 14.2005,7(14),3131-3134. *

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