CN109912489B - Method for synthesizing 2, 3-dihydrotryptamine compound by alkylation of non-activated olefin - Google Patents

Method for synthesizing 2, 3-dihydrotryptamine compound by alkylation of non-activated olefin Download PDF

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CN109912489B
CN109912489B CN201910178150.4A CN201910178150A CN109912489B CN 109912489 B CN109912489 B CN 109912489B CN 201910178150 A CN201910178150 A CN 201910178150A CN 109912489 B CN109912489 B CN 109912489B
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刘颖杰
杨四萍
于淼
许颖
吴健
梁德强
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Harbin University of Commerce
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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Abstract

The invention provides a method for synthesizing 2, 3-dihydrotryptamine compounds by alkylation of non-activated olefin, which uses non-activated olefinNThe allyl aniline derivative is used as raw material and is reacted with amideexoAnd (3) carrying out selective amino alkylation/cyclization cascade reaction to generate the 2, 3-dihydrotryptamine compound. The method has the advantages that no metal catalyst participates in the reaction process, the reaction solvent is a mixed water phase solvent formed by amide and water, the solvent cost is greatly reduced, the post-treatment operation steps are simplified, meanwhile, the substrate selection range is wide, the process conditions are simple, the production cost is low, and the method is suitable for large-scale application.

Description

Method for synthesizing 2, 3-dihydrotryptamine compound by alkylation of non-activated olefin
Technical Field
The invention particularly relates to a synthesis method of a2, 3-dihydrotryptamine compound, belonging to the technical field of organic synthesis.
Background
Tryptamine is an important skeleton structure for constructing natural products and medicines, and various chemical substances with biological activity, such as panobinostat for treating multiple myeloma, naratriptan, sumatriptan, rizatriptan, eletriptan, almotriptan, zolmitriptan and the like for treating migraine can be synthesized through series of tryptamine derivatives. 2, 3-dihydrotryptamine derivatives widely present in alkaloid and clinical drug molecules are important lead compounds for new drug design (ref 1: D.M.Krueger, A.Glas, D.bier, N.Pospiech, K.Wallarven, L.Dietrich, C.Ottmann, O.Koch, S.Hennig and T.N.Grossmann, J.Med.Chem.,2017,60,8982, 8988; ref 2: D.Decalo and M.K.Hadden, Eur.J.Med.Chem.,2012,56,179 194), 2, 3-dihydrotryptamine is commonly obtained in the prior art by derivatization of parent tryptamine (ref 3: Y.J.az, Z.A.Dipage, A.S.Knight, N.J.trewat, J.trewR.R.3562, Eumk.J.35J.R.357, C.J.J.J.J.Checker.3523, Euhrn.J.J.D.J.D.D.D.D.D.K.Haddiden, E.D.D.D.D.J.Chem.C.Chem.C.Chem.t., 56, C.J.J.Z.J.J.J.J.J.D.D.E.E.E.E.E.C.C.E.T.T.T.t.T.T.H.H.H.H.S.H.H.H.H.H.S.S.H.H.S.H.H.H.H.H.H.S.H.S.S.H.H.H.H.S.H.H.S.S.S.H.S.E.E.E.E.D.E.E.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.C.D.D.C.C.D.D.D.C.C.C.D.D.D.D.D.D.C.C.C.C.D.C.C.C.D.D.D.D.D.C.D.D.D.C.C.C.C.C.C.C.D.D.C.C.D.D.C.D.D.C.C.C.C.C.D.D.D.D.D.D.D.C.C.C.C.D.D.C.D.D.C.C.C.D.C.C.D.C.C.C.C.D.D.D.D.D.D.D.D.D.D.D.D.D.D.C.D.D.D.D.C.C.C.C.C.C.C.C.C.C.D.C.C.D.D.D.D.C.C.D.D.D.D.D.D.C.C.C.D.D.C.C.D.D.C.C.C.C.C.C.C.C.C.C.C.C.C.C.C.C.
Figure BDA0001989255010000011
Org. lett.,2011,13, 5124-. In addition, by parent tryptamine derivatizationThe harsh conditions of high temperature and high pressure are usually required, and the reliance on Bronsted or Lewis acid catalysts, as well as transition metal catalysts, leads to difficult removal of the transition metal residues in the product, thereby limiting industrial application.
Disclosure of Invention
In order to solve the problems in the prior art, the invention aims to provide a method for synthesizing a2, 3-dihydrotryptamine compound, the method takes a non-activated olefin N-allylaniline derivative as a raw material to perform exo-selective amino alkylation/cyclization cascade reaction with amide to generate the 2, 3-dihydrotryptamine compound, and the method has the advantages of wide substrate selection range, simple process conditions, low production cost and suitability for large-scale application.
The purpose of the invention is realized as follows:
a synthetic method of a2, 3-dihydrotryptamine compound (a compound shown in a formula II) is characterized in that the reaction route is as follows:
Figure BDA0001989255010000021
wherein:
R1is hydrogen or C1-6An alkyl group;
R2is hydrogen, halogen, C1-6Alkyl or phenyl;
R3is COR7Or SO2R8；
R4Is hydrogen or C1-6An alkyl group;
R5is hydrogen or C1-6An alkyl group;
R6is hydrogen or C1-6An alkyl group;
R7is C1-17Alkyl or-O-C1-6An alkyl group;
R8is C1-6An alkyl group.
In one embodiment of the present invention, when R is as described above4、R5When five-membered rings are formed, the synthetic route of the invention is as follows:
Figure BDA0001989255010000022
R1、R2、R3、R6、R7、R8as defined hereinbefore.
In one embodiment of the invention, the catalyst is selected from DCP, DTBP, BPO, TBHP, Oxone, TBPB, K2S2O8Etc.; DCP is preferred, and is preferably used in an amount of 2 to 3 equivalents.
In one embodiment of the invention, the solvent used in the invention is a mixed aqueous phase solvent formed by the compound (amide) of the formula III and water, wherein the volume ratio of the compound of the formula III to the water is 3-5: 1. Furthermore, the reaction temperature of the invention is 120 plus or minus 5 ℃ (115 ℃ -125 ℃).
In one embodiment of the present invention, R is1Selected from hydrogen or methyl; r2Selected from hydrogen, methyl, chlorine, bromine or phenyl; r3Is COR7；R4Is hydrogen, methyl or ethyl; r is5Selected from hydrogen, methyl or ethyl; r6Selected from hydrogen, methyl or ethyl; r7Selected from methyl, ethyl, tert-butyl, n-C7H15、n-C9H19、n-C11H23Or n-C17H35。
An embodiment of the present invention includes wherein R2A compound (formula I) which is phenyl, unsubstituted or substituted by one or more of the following groups: hydrogen, methyl, chlorine, bromine or phenyl; in the compounds of the formula I, R1Can be independently ortho-position, meta-position or para-position, can be simultaneously substituted by the ortho-position, the meta-position or/and the para-position, and can also be independently substituted.
The compound of formula II of the present invention is selected from the group consisting of the compounds 2a-2k, as shown in Table 1 below.
TABLE 12 a-2n Compounds
Figure BDA0001989255010000031
Figure BDA0001989255010000041
Advantageous effects
The invention provides a method for synthesizing 2, 3-dihydrotryptamine compounds by alkylation of non-activated olefin, which takes non-activated olefin N-allylaniline derivatives as raw materials to perform exo-selective ammonia alkylation/cyclization cascade reaction with amide to generate the 2, 3-dihydrotryptamine compounds. The invention provides a method for synthesizing 2, 3-dihydrotryptamine derivatives from acyclic raw materials, and relates to simple amide alpha-C (sp) of non-activated olefin3) A rare case of-H bond functionalization reactions. The reaction process of the invention has no metal catalyst, and the problem of residual transition metal in the product is not worried about, meanwhile, the solvent is a mixed aqueous phase solvent formed by the raw material amide and water, and the reaction process does not involve other organic solvents, thereby not only greatly reducing the cost of the solvent, but also simplifying the post-treatment operation steps, and having remarkable economic value.
Detailed Description
Definition of
The term "halogen" as used herein means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
The term "C" as used in the present invention1-6Alkyl "means a saturated straight or branched chain hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl and the like, preferably methyl, ethyl, propyl, isopropyl, tert-butyl or isobutyl.
The term "C" as used herein1-17Alkyl "means a saturated, straight-chain or branched-chain hydrocarbon group having from 1 to 17 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-C7H15、n-C9H19、n-C11H23、n-C17H35And the like.
The term "-O-C" as used in the present invention1-6Alkyl "means a saturated straight or branched chain alkoxy group having 1 to 6 carbon atoms, such as methoxy, ethoxy, t-butoxy, and the like.
Examples
In order to make the objects and technical solutions of the present invention clearer, preferred embodiments of the present invention are described in detail below. It is to be noted that: the following examples are intended to illustrate the invention further and are not to be construed as limiting the scope of the invention. The invention is not limited to the embodiments described above, but rather, many modifications and variations may be made by one skilled in the art without departing from the scope of the invention. The starting compounds of formula I and formula III of the present invention are commercially available or can be prepared by reference to the literature (literature 5: D. Liang, Q. Dong, P. xu, Y. Dong, W. Li, Y. Ma, J. org. chem.2018,83, 11978-11986; literature 6: S.O' Sullivan, E.Doni, T.Tuttle, J.A.Murphy.Angew.chem.int.Ed.2014,53, 474-478; Angew.chem.2014,126, 484-488; literature 7: Z.Wu, S.Li, H.Xu.Angew.chem.Ed.2018, 57, 14070-14074; Angew.2018, 130, 66-14270; CN 201811634880.2).
Example 1
The non-activated olefin alkylation is used for synthesizing 2, 3-dihydrotryptamine (taking the synthesis example of 2a 1), and the reaction route is as follows:
Figure BDA0001989255010000051
the method comprises the following operation steps: to a 10mL Schlenk tube equipped with a magnetic stirrer, N- (2-methylallyl) -N-phenylacetamide 1a1(38mg, 0.2mmol), dicumyl peroxide (DCP, 162mg, 0.6mmol), N, N-dimethylaniline (DMA, 1.0mL) and water (0.2mL) were added sequentially under argon. The mixture was reacted at 120 ℃ for 6h, cooled and then saturated Na2S2O3Quenched (0.5mL) with water (5.0mL) and then with CH2Cl2Extracted three times (10.0 mL). The organic phases are combined and the organic solvent is distilled off. Column chromatography of the residue using silica gel (300-400 mesh) was performed (petroleum ether-acetone-6/1, v/v) to give 2a1(39mg, 7) as a pale yellow oil1% yield).
Referring to example 1, the effect of the catalyst, solvent and temperature on the reaction was examined, and the details are shown in Table 2.
TABLE 2 influence of catalyst, solvent, temperature on the reactiona
Figure BDA0001989255010000052
Figure BDA0001989255010000061
aReaction conditions are as follows: 1a1(0.2mmol), solvent (1.2mL), Ar, 6 h.bAdding Cu2O (10 mol%) was used as a composite catalyst.c5.0-6.0mol/L decane solution.d10equiv of DMA was added.ev/v.
The inventors began the present study with the amino alkylation/cyclization cascade of N- (2-methylpropenyl) acetanilide 1a1 and N, N-Dimethylacetamide (DMA) (Table 2). Mixing 1a1 with 10 mol% Cu in 120 ℃ DMA solvent2O and 3 equivalents of di-tert-butyl peroxide (DTBP) gave after 6h a 36% yield of 2, 3-dihydrotryptamine product 2a1 (serial No. 1). The copper catalyst was not necessary and was removed to give a comparable yield (number 2). When dicumyl peroxide (DCP) was used as a catalyst for initiating the reaction, the yield of 2, 3-dihydrotryptamine 2a1 increased to 44% (No. 3), while the yield decreased slightly when tert-butyl perbenzoate (TBPB) (No. 4). Other catalysts, e.g. dibenzoyl peroxide (BPO), tert-butyl peroxide (TBHP), K2S2O8And Oxone, were ineffective for this reaction (sequence No. 5). Attempts to carry out the reaction in other solvents using 10 equivalents of DMA were unsuccessful (Nos. 6-8). When the reaction was carried out in 1, 2-dichloroethane (DCE, No. 6) or toluene (No. 7), the yield of 2, 3-dihydrotryptamine 2a1 was extremely low, while only trace amounts of 2a1 were observed in the reaction in other polar solvents. These tested polar solvents include Tetrahydrofuran (THF), CH3NO2Dimethyl sulfoxide (DMSO) and ethanol(No. 8). Surprisingly, the solvent was replaced by DMA/H2The yield of the dihydrotryptamine 2a1 was improved to 71% (No. 9) when O (5:1, v/v) was mixed; however, further increase of the proportion of water in the mixed solvent resulted in decrease of the yield (Nos. 10 to 12).
With reference to the above examples, the influence of the substrate on the reaction according to the invention was investigated under optimum reaction conditions, as specified in Table 3 below.
TABLE 3 Synthesis of 2, 3-dihydrotryptamine from N-allylanilinea
Figure BDA0001989255010000062
Figure BDA0001989255010000071
The experimental results showed that N- (2-methylallyl) acetanilide having a methyl, bromo or chloro atom in the para-position of the N-aryl group reacted with DMA to give the 5-substituted 2, 3-dihydrotryptamine 2a2-4 in 68-76% yield, whereas the 5-phenyl product 2a5 was only moderately produced. N-Protecting Groups (PG) such as propionyl, octanoyl, decanoyl and dodecanoyl are also compatible with this reaction, and the corresponding 2, 3-dihydrotryptamine product 2b-e is synthesized from allylated amides bearing neutral, electron-rich or electron-poor N-aryl groups in moderate to high yields. When pivaloyl group is used as the N-protecting group, indoline was produced in a high yield of 2 g. Tert-butyloxycarbonyl and ethylsulfonyl are also useful protecting groups, corresponding to dihydrotryptamine product 2h1,2 in 61% and 44% yields, respectively. Allylated acetanilides with 3-chloro substituents were also highly reactive substrates, giving 43% yield of 4-chlorodihydrotryptamine 2 j.
According to the Bowdin's rule, 6-endo-trig type cyclization is probably a competitive reaction of this reaction. Therefore, in order to avoid this competition process, N- (2-methylallyl) aniline was used as a substrate in the initial studies. After exo selectivity was achieved in all of the above reactions, the inventors attempted to extend the reaction to normal N-allylaniline without methyl branching. Interestingly, 2k corresponding to the 5-exo-trig product was produced exclusively in 60% yield, and no endo product was still detected.
The inventors continued to investigate the scope of amide solvents. When N, N-Dimethylformamide (DMF)/H2When the O mixture was used as a solvent, 2l of the objective 2, 3-dihydrotryptamine was produced in a yield of 36%. Using aqueous N-methylpyrrolidone (NMP) as substrate, 2m corresponding to the aminoalkylated indoline product was produced in high yield. It is appreciated that the present aminoalkylation/cyclization cascade can also be extended to N-methylacetamide solvents. N-methylacetamide has an unprotected amide N-H bond, resulting in its past use in the amide alpha-C (sp)3) the-H bond functionalization reaction cannot be used. This reaction can produce an intermediate yield of the acetyl protected primary amine 2 n. Thus, the present invention presents a general method for the simultaneous synthesis of secondary and primary 2, 3-dihydrotryptamines.
In summary, the present invention reports a metal-free, exo-selective aminoalkylation/cyclization cascade of N-allylanilines. The reaction is the first example of the synthesis of 2, 3-dihydrotryptamine derivatives starting from acyclic starting materials, and is also a simple amide alpha-C (sp) involving an unactivated olefin3) A rare case of-H bond functionalization reactions. The reaction of the invention is carried out in mixed aqueous phase, and the invention has wide range of substrates, simple condition and low cost.
Nuclear magnetic data of target product
Figure BDA0001989255010000081
2a1, N- (2- (1-acetyl-3-methylindolin-3-yl) ethyl) -N-methylacetamide, the rotation of the N- (CO) bond is hindered to generate a light yellow liquid, which is a mixture of four inseparable rotamers (the major and minor isomers are respectively represented by major and minor, and the other 2 rotamers are less abundant and therefore not characterized, and only the major and minor isomers are characterized) with a ratio of 20:10:3: 2.1H NMR(400MHz,CDCl3)δ＝1.38(s,3H major),1.43(s,3H minor),1.79-1.98(stack,2H major and 5H minor),2.02(s,3H major),2.24(s,3H minor),2.25(s,3H major),2.84(s,3H minor),2.87(s,3H major),2.95-3.04(stack,1H major and 1H minor),3.16-3.24(m,1H minor),3.42-3.49(m,1H major),3.72(d,J＝10.4Hz,1H major),3.78(d,J＝10.3Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.11(d,J＝10.4Hz,1H major),7.03-7.13(stack,2H major and 2H minor),7.19-7.27(stack,1H major and 1H minor),8.19(d,J＝8.1Hz,1H major),8.22(d,J＝8.1Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.32(major),169.98(minor),168.82(major),168.50(minor),142.12(minor),142.08(major),138.17(major),136.95(minor),128.50(minor),128.03(major),124.07(minor),123.81(major),122.07(major),122.00(minor),117.18(minor),117.00(major),61.11(minor),60.78(major),46.84(minor),44.11(major),42.53(major),42.30(minor),39.82(minor),38.33(major),36.24(major),33.26(minor),27.19(major and minor),24.32(major),24.29(minor),21.82(major),20.92(minor)；HRMS(ESI-TOF)Calcd for C16H23N2O2 +([M+H]+)275.1754.Found 275.1762.
Figure BDA0001989255010000091
2a2, N- (2- (1-acetyl-3, 5-dimethyl indolin-3-yl) ethyl) -N-methylacetamide, the rotation of the N- (CO) bond is hindered to generate a mixture of 26:13:4:3 four inseparable rotamers (the main isomer and the minor isomer are respectively represented by major and minor, and the content of the other 2 rotamers is less, so that the isomers are not characterized, and only the major and minor isomers are characterized), and the yellow liquid is obtained.1H NMR(400MHz,CDCl3)δ＝1.36(s,3H major),1.42(s,3H minor),1.77-1.97(stack,2H major and 5H minor),2.02(s,3H major),2.22(s,3H minor),2.23(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.85(s,3H minor),2.88(s,3H major),2.96-3.05(stack,1H major and 1H minor),3.16-3.24(m,1H minor),3.42-3.49(m,1H major),3.70(d,J＝10.4Hz,1H major),3.76(d,J＝10.4Hz,1H minor),3.85(d,J＝10.4Hz,1H minor),4.09(d,J＝10.4Hz,1H major),6.92(s,1H major),7.01(d,J＝7.2Hz,1H major,and brs(stack),1H minor),7.05(d,J＝7.6Hz,1H minor),8.05(d,J＝8.2Hz,1H major),8.08(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.31(major),169.98(minor),168.47(major),168.16(minor),139.86(minor),139.81(major),138.31(major),137.11(minor),133.74(minor),133.38(major),128.97(minor),128.52(major),122.64(major),122.53(minor),116.91(minor),116.73(major),61.24(minor),60.97(major),46.87(minor),44.14(major),42.48(major),42.26(minor),39.82(minor),38.34(major),36.26(major),33.26(minor),27.13(minor),27.09(major),24.20(major),24.17(minor),21.82(major),21.14(major and minor),20.88(minor)；HRMS(ESI-TOF)Calcd for C17H25N2O2 +([M+H]+)289.1911.Found 289.1913.
Figure BDA0001989255010000092
2a3, N- (2- (1-acetyl-5-bromo-3-methylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation resistance generated 4:1 inseparable rotamer mixture (two other isomers due to acylanilide N- (CO) rotation resistance, the obtained amount was little and not characterized), light yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.37(s,3H major),1.43(s,3H minor),1.78-1.91(stack,2H major and 2H minor),1.95(s,3H minor),2.02(s,3H major),2.23(s,3H minor),2.24(s,3H major),2.86(s,3H minor),2.90(s,3H major),2.93-3.07(stack,1H major and 1H minor),3.18-3.26(m,1H minor),3.42-3.49(m,1H major),3.72(d,J＝10.5Hz,1H major),3.79(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.16(d,J＝10.4Hz,1H major),7.21(d,J＝2.0Hz,1H major),7.22(d,J＝1.8Hz,1H minor),7.32(dd,J＝2.1,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.08(d,J＝8.6Hz,1H major),8.11(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.41(major),169.92(minor),168.93(major),168.54(minor),141.24(major),141.21(minor),140.62(major),139.38(minor),131.44(minor),130.96(major),125.28(major and minor),118.71(minor),118.54(major),116.44(minor),116.12(major),61.18(minor),60.78(major),46.72(minor),43.99(major),42.66(major),42.40(minor),39.65(minor),38.35(major),36.33(major),33.31(minor),27.09(major),27.01(minor),24.22(major),24.18(minor),21.81(major),20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22BrN2O2 +([M+H]+)353.0859.Found 353.0858.
Figure BDA0001989255010000101
2a4, N- (2- (1-acetyl-5-chloro-3-methylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to produce a 7:2 inseparable rotamer mixture (the other two isomers were produced due to anilide N- (CO) rotation hindered, obtained in small amounts not characterized), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.37(s,3H major),1.43(s,3H minor),1.78-1.90(stack,2H major and 2H minor),1.95(s,3H minor),2.03(s,3H major),2.24(s,3H minor),2.25(s,3H major),2.86(s,3H minor),2.90(s,3H major),2.95-3.04(stack,1H major and 1H minor),3.18-3.26(m,1H minor),3.42-3.50(m,1H major),3.73(d,J＝10.4Hz,1H major),3.80(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.17(d,J＝10.4Hz,1H major),7.07(d,J＝2.1Hz,1H major),7.08(d,J＝2.2Hz,1H minor),7.17(dd,J＝2.2,8.6Hz,1H major),7.22(dd,J＝2.2,8.6Hz,1H minor),8.13(d,J＝8.6Hz,1H major),8.16(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.42(major),169.93(minor),168.88(major),168.50(minor),140.73(major),140.70(minor),140.21(major),138.99(minor),128.99(minor),128.62(major),128.50(minor),128.03(major),122.37(major),122.34(minor),118.23(minor),118.04(major),61.22(minor),60.81(major),46.72(minor),43.98(major),42.65(major),42.39(minor),39.60(minor),38.29(major),36.33(major),33.32(minor),27.07(major),26.99(minor),24.20(major),24.16(minor),21.81(major),20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22ClN2O2 +([M+H]+)309.1364.Found 309.1362.
Figure BDA0001989255010000111
2a5, N- (2- (1-acetyl-3-methyl-5-phenylindolin-3-yl) ethyl) -N-methylacetamide, N- (CO) bond rotation being hindered to give a mixture of four inseparable rotamers 13:5:1:2 (major and minor are denoted major and minor respectively, and in addition 2 are less abundant and therefore not characterized, only major and minor isomers), white solid: mp 145-146 ℃.1H NMR(400MHz,CDCl3)δ＝1.44(s,3H major),1.48(s,3H minor),1.85-1.97(stack,2H major and 5H minor),2.02(s,3H major),2.26(s,3H minor),2.28(s,3H major),2.86(s,3H minor),2.88(s,3H major),3.01-3.11(stack,1H major and 1H minor),3.21-3.30(m,1H minor),3.46-3.53(m,1H major),3.77(d,J＝10.4Hz,1H major),3.83(d,J＝10.4Hz,1H minor),3.92(d,J＝10.4Hz,1H minor),4.17(d,J＝10.4Hz,1H major),7.30-7.59(stack,7H major and 7H minor),8.24(d,J＝8.4Hz,1H major),8.27(d,J＝8.7Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.38(major),169.96(minor),168.82(major),168.46(minor),141.55(major),141.53(minor),140.92(major),140.68(minor),138.92(major),137.69(minor),137.40(minor),136.98(major),128.87(minor),128.78(major),127.56(minor),127.21(minor),127.06(major),127.00(major),126.86(major and minor),120.70(major),120.62(minor),117.38(minor),117.20(major),61.40(minor),61.07(major),46.88(minor),44.16(major),42.64(major),42.41(minor),39.91(minor),38.45(major),36.30(major),33.32(minor),27.20(major),27.14(minor),24.28(major),24.25(minor),21.82(major),20.94(minor)；HRMS(ESI-TOF)Calcd for C22H27N2O2 +([M+H]+)351.2067.Found 351.2079.
Figure BDA0001989255010000112
2b1, N- (2- (3, 5-dimethyl-1-propionylindolin-3-yl) ethyl) -N-methylacetamide, hindered rotation of the DMA N- (CO) bond to give a 2:1 inseparable mixture of rotamers (the other two isomers were produced in small amounts, uncharacterized, due to hindered rotation of the anilide N- (CO)), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.21-1.26(stack,3H major and 3H minor),1.36(s,3H major),1.41(s,3H minor),1.76-1.96(stack,2H major and 5H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.38-2.56(stack,2H major and 2H minor),2.84(s,3H minor),2.87(s,3H major),2.91-3.04(stack,1H major and 1H minor),3.14-3.22(m,1H minor),3.42-3.50(m,1H major),3.68(d,J＝10.4Hz,1H major),3.74(d,J＝10.4Hz,1H minor),3.84(d,J＝10.4Hz,1H minor),4.08(d,J＝10.4Hz,1H major),6.91(s,1H major),7.01(d,J＝8.2Hz,1H major,and brs(stack),1H minor),7.05(d,J＝8.3Hz,1H minor),8.09(d,J＝8.3Hz,1H major),8.12(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.82(major),171.54(minor),170.32(major),170.01(minor),140.07(minor),140.04(major),138.13(major),136.95(minor),133.59(minor),133.22(major),128.99(minor),128.55(major),122.61(major),122.51(minor),116.84(minor),116.66(major),60.26(minor),60.00(major),46.88(minor),44.15(major),42.46(major),42.24(minor),39.86(minor),38.41(major),36.26(major),33.27(minor),29.18(minor),29.14(major),27.14(minor),27.11(major),21.84(major),21.14(major),21.12(minor),20.89(minor),8.73(major and minor)；HRMS(ESI-TOF)Calcd for C18H27N2O2 +([M+H]+)303.2067.Found 303.2068.
Figure BDA0001989255010000121
2b2, N- (2- (5-bromo-3-methyl-1-propionylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to yield a 3:1 inseparable rotamer mixture as a light yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.20-1.26(stack,3H major and 3H minor),1.36(s,3H major),1.42(s,3H minor),1.77-1.91(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.38-2.57(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.93-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.42-3.50(m,1H major),3.70(d,J＝10.4Hz,1H major),3.77(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.15(d,J＝10.4Hz,1H major),7.21(s,1H major),7.22(s,1H minor),7.32(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝1.9,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝172.26(major),171.93(minor),170.39(major),169.92(minor),141.48(major and minor),140.48(major),139.28(minor),131.42(minor),130.95(major),125.25(major and minor),118.61(minor),118.43(major),116.22(minor),115.92(major),60.22(minor),59.84(major),46.73(minor),43.99(major),42.65(major),42.39(minor),39.67(minor),38.40(major),36.32(major),33.30(minor),29.24(minor),29.19(major),27.10(major),26.99(minor),21.81(major),20.95(minor),8.60(major and minor)；HRMS(ESI-TOF)Calcd for C17H24BrN2O2 +([M+H]+)367.1016.Found 367.1014.
Figure BDA0001989255010000122
2b3, N- (2- (5-chloro-3-methyl-1-propionylindolin-3-yl) ethyl) -N-methylacetamide, blocked from rotation at the DMAN- (CO) bond, produced a mixture of rotamers inseparable at 3:1, as a pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.20-1.26(stack,3H major and 3H minor),1.37(s,3H major),1.42(s,3H minor),1.77-1.91(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.38-2.58(stack,2H major and 2H minor),2.85(s,3H minor),2.90(s,3H major),2.92-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.42-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.16(d,J＝10.4Hz,1H major),7.07(s,1H major),7.08(s,1H minor),7.17(dd,J＝1.6,8.6Hz,1H major),7.22(dd,J＝1.6,8.6Hz,1H minor),8.16(d,J＝8.6Hz,1H major),8.19(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝172.21(major),171.88(minor),170.41(major),169.94(minor),140.99(major and minor),140.08(major),138.89(minor),128.81(minor),128.48(minor),128.44(major),128.02(major),122.35(major and minor),118.15(minor),117.95(major),60.28(minor),59.90(major),46.74(minor),44.00(major),42.65(major),42.40(minor),39.64(minor),38.36(major),36.32(major),33.31(minor),29.20(minor),29.15(major),27.08(major),26.97(minor),21.80(major),20.95(minor),8.62(major and minor)；HRMS(ESI-TOF)Calcd for C17H24ClN2O2 +([M+H]+)323.1521.Found 323.1521.
Figure BDA0001989255010000131
2c1, N-methyl-N- (2- (3-methyl-1-octanoyl indolin-3-yl) ethyl) acetamide, blocked by rotation of the DMAN- (CO) bond to give a 2:1 inseparable mixture of rotamers (the other two isomers were produced due to blocked rotation of the anilide N- (CO) and were obtained in small amounts and were not characterized), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝6.7Hz,3H major and 3H minor),1.26-1.43(stack,11H major and 11H minor),1.70-1.96(stack,4H major and 7H minor),2.02(s,3H major),2.37-2.52(stack,2H major and 2H minor),2.84(s,3H minor),2.87(s,3H major),2.91-3.03(stack,1H major and 1H minor),3.15-3.23(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.77(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.09(d,J＝10.4Hz,1H major),7.02-7.13(stack,2H major and 2H minor),7.19-7.27(stack,1H major and 1H minor),8.22(d,J＝8.2Hz,1H major),8.25(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.62(major),171.35(minor),170.31(major),170.00(minor),142.37(minor),142.33(major),138.05(major),136.84(minor),128.52(minor),128.06(major),123.94(minor),123.67(major),122.03(major),121.94(minor),117.23(minor),117.05(major),60.37(minor),60.03(major),46.87(minor),44.17(major),42.50(major),42.26(minor),39.90(minor),38.24(major),36.24(major),36.14(minor),36.09(major),33.27(minor),31.74(major),31.72(minor),29.36(major and minor),29.17(major),29.15(minor),27.25(major),27.13(minor),24.61(minor),24.54(major),22.63(major and minor),21.82(major),20.92(minor),14.10(major),14.09(minor)；HRMS(ESI-TOF)Calcd for C22H35N2O2 +([M+H]+)359.2693.Found 359.2696.
Figure BDA0001989255010000141
2c2, N- (2- (3, 5-dimethyl-1-octanoylindolin-3-yl) ethyl) -N-methylacetamide, blocked by rotation of the DMAN- (CO) bond, produced a mixture of 2:1 inseparable rotamers (the other two isomers were produced due to blocked rotation of the anilide N- (CO), were obtained in small amounts and were not characterized), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝6.8Hz,3H major and 3H minor),1.26-1.41(stack,11H major and 11H minor),1.69-1.96(stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.36-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.93-3.05(stack,1H major and 1H minor),3.15-3.23(m,1H minor),3.42-3.50(m,1H major),3.69(d,J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1H minor),3.86(d,J＝10.4Hz,1H minor),4.07(d,J＝10.4Hz,1H major),6.91(s,1H major),7.01(dd,J＝0.9,8.2Hz,1H major,and brs(stack),1H minor),7.05(dd,J＝0.7,8.1Hz,1H minor),8.09(d,J＝8.3Hz,1H major),8.11(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.26(major),171.00(minor),170.28(major),169.97(minor),140.08(minor),140.03(major),138.19(major),137.01(minor),133.57(minor),133.20(major),128.95(minor),128.51(major),122.60(major),122.48(minor),116.93(minor),116.74(major),60.46(minor),60.19(major),46.87(minor),44.16(major),42.43(major),42.21(minor),39.88(minor),38.23(major),36.24(major),36.01(minor),35.97(major),33.25(minor),31.73(major),31.70(minor),29.36(major and minor),29.17(major),29.15(minor),27.14(major),27.07(minor),24.63(minor),24.57(major),22.62(major and minor),21.82(major),21.12(major and minor),20.87(minor),14.10(major),14.08(minor)；HRMS(ESI-TOF)Calcd for C23H37N2O2 +([M+H]+)373.2850.Found 373.2853.
Figure BDA0001989255010000142
2c3, N- (2- (5-bromo-3-methyl-1-octanoylindolin-3-yl) ethyl) -N-methylacetamide, blocked from rotation by the DMAN- (CO) bond, produced a 3:1 inseparable mixture of rotamers as a pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝6.8Hz,3H major and 3H minor),1.30-1.42(stack,11H major and 11H minor),1.68-1.75(stack,2H major and 2H minor),1.77-1.90(stack,2H major and 2H minor),1.94(s,3H minor),2.03(s,3H major),2.36-2.51(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.94-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.21(d,J＝1.8Hz,1H major),7.22(d,J＝1.8Hz,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.72(major),171.40(minor),170.37(major),169.90(minor),141.45(major and minor),140.52(major),139.32(minor),131.38(minor),130.91(major),125.24(major and minor),118.68(minor),118.49(major),116.22(minor),115.92(major),60.39(minor),59.99(major),46.72(minor),44.00(major),42.61(major),42.35(minor),39.68(minor),38.21(major),36.32(major),36.03(minor),35.97(major),33.30(minor),31.72(major),31.69(minor),29.32(minor),29.30(major),29.16(major),29.13(minor),27.16(major),26.94(minor),24.49(minor),24.42(major),22.63(major and minor),21.82(major),20.96(minor),14.11(major),14.09(minor)；HRMS(ESI-TOF)Calcd for C22H34BrN2O2 +([M+H]+)437.1798.Found 437.1799.
Figure BDA0001989255010000151
2c4, N- (2- (5-chloro-3-methyl-1-octanoylindolin-3-yl) ethyl) -N-methylacetamide, rotation of the DMAN- (CO) bond was hindered to give a 3:1 inseparable rotamer mixture, a white solid: mp 96-97 ℃.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝6.7Hz,3H major and 3H minor),1.25-1.42(stack,11H major and11H minor),1.68-1.77(stack,2H major and 2H minor),1.78-1.92(stack,2H major and 2H minor),1.95(s,3H minor),2.03(s,3H major),2.36-2.51(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.93-3.07(stack,1H major and 1H minor),3.17-3.28(m,1H minor),3.43-3.51(m,1H major),3.72(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.88(d,J＝10.4Hz,1H minor),4.14(d,J＝10.4Hz,1H major),7.06(d,J＝2.0Hz,1H major),7.07(d,J＝2.0Hz,1H minor),7.17(dd,J＝2.2,8.6Hz,1H major),7.22(dd,J＝2.2,8.6Hz,1H minor),8.16(d,J＝8.6Hz,1H major),8.19(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.68(major),171.35(minor),170.38(major),169.92(minor),140.97(major and minor),140.08(major),138.89(minor),128.82(minor),128.49(minor),128.44(major),128.02(major),122.33(major),122.29(minor),118.25(minor),118.04(major),60.46(minor),60.06(major),46.73(minor),44.02(major),42.61(major),42.35(minor),39.67(minor),38.19(major),36.32(major),36.01(minor),35.95(major),33.32(minor),31.73(major),31.70(minor),29.34(minor),29.32(major),29.17(major),29.14(minor),27.16(major),26.95(minor),24.52(minor),24.44(major),22.64(major and minor),21.83(major),20.97(minor),14.11(major),14.10(minor)；HRMS(ESI-TOF)Calcd for C22H34ClN2O2 +([M+H]+)393.2303.Found 393.2307.
Figure BDA0001989255010000161
2d1, N- (2- (1-decanoyl-3, 5-dimethylindolin-3-yl) ethyl) -N-methylacetamide, hindered rotation of the DMAN- (CO) bond produced a 2:1 inseparable mixture of rotamers (the other two isomers were produced due to hindered rotation of the anilide N- (CO) and were obtained in small amounts and not characterized), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.27-1.41(stack,15H major and 15H minor),1.68-1.96(stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.35-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.95-3.05(stack,1H major and 1H minor),3.15-3.23(m,1H minor),3.42-3.49(m,1H major),3.69(d,J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1H minor),3.86(d,J＝10.4Hz,1H minor),4.07(d,J＝10.4Hz,1H major),6.91(s,1H major),7.00(d,J＝8.1Hz,1H major,and brs(stack),1H minor),7.05(d,J＝8.0Hz,1H minor),8.09(d,J＝8.3Hz,1H major),8.11(d,J＝8.3Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.25(major),171.00(minor),170.27(major),169.96(minor),140.08(minor),140.02(major),138.19(major),137.01(minor),133.55(minor),133.19(major),128.94(minor),128.50(major),122.60(major),122.48(minor),116.92(minor),116.73(major),60.45(minor),60.18(major),46.87(minor),44.15(major),42.43(major),42.20(minor),39.87(minor),38.23(major),36.23(major),36.01(minor),35.96(major),33.24(minor),31.87(major),31.85(minor),29.51,29.48,29.46,29.40,29.28,27.14(major),27.06(minor),24.63(minor),24.57(major),22.65(major and minor),21.81(major),21.12(major),21.09(minor),20.86(minor),14.10(major and minor)；HRMS(ESI-TOF)Calcd for C25H41N2O2 +([M+H]+)401.3163.Found 401.3165.
Figure BDA0001989255010000162
2d2, N- (2- (5-bromo-1-decanoyl-3-methylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to yield a 3:1 inseparable rotamer mixture, white solid: mp 80-81 ℃.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.27-1.42(stack,15H major and15H minor),1.68-1.73(stack,2H major and 2H minor),1.77-1.90(stack,2H major and 2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.51(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.94-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.21(s,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.73(major),171.40(minor),170.37(major),169.91(minor),141.46(major and minor),140.51(major),139.30(minor),131.40(minor),130.94(major),125.24(major and minor),118.70(minor),118.52(major),116.24(minor),115.93(major),60.41(minor),60.01(major),46.73(minor),44.01(major),42.62(major),42.36(minor),39.70(minor),38.22(major),36.32(major),36.05(minor),35.99(major),33.31(minor),31.89(major),31.87(minor),29.51,29.48,29.36,29.29,27.17(major),26.95(minor),24.50(minor),24.43(major),22.67(major and minor),21.82(major),20.95(minor),14.12(major and minor)；HRMS(ESI-TOF)Calcd for C24H38BrN2O2 +([M+H]+)465.2111.Found465.2107.
Figure BDA0001989255010000171
2e1, N- (2- (1-dodecanoyl-3, 5-dimethylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hinderedA2: 1 inseparable rotamer mixture was produced (the other two isomers were produced due to hindered N- (CO) rotation of the anilide, and were obtained in small amounts, uncharacterized), as a yellowish liquid.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.41(stack,19H major and 19H minor),1.68-1.97(stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.36-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.94-3.05(stack,1H major and 1H minor),3.15-3.23(m,1H minor),3.42-3.50(m,1H major),3.69(d,J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1H minor),3.86(d,J＝10.4Hz,1H minor),4.07(d,J＝10.4Hz,1H major),6.92(s,1H major),7.01(d,J＝7.9Hz,1H major,and brs(stack),1H minor),7.05(d,J＝8.1Hz,1H minor),8.09(d,J＝8.4Hz,1H major),8.11(d,J＝8.4Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.27(major),171.01(minor),170.29(major),169.98(minor),140.07(minor),140.02(major),138.18(major),137.00(minor),133.57(minor),133.20(major),128.95(minor),128.51(major),122.61(major),122.49(minor),116.91(minor),116.73(major),60.45(minor),60.17(major),46.88(minor),44.16(major),42.43(major),42.20(minor),39.87(minor),38.23(major),36.25(major),36.02(minor),35.97(major),33.25(minor),31.90(major and minor),29.63,29.53,29.41,29.33,27.16(major),27.08(minor),24.63(minor),24.57(major),22.68(major and minor),21.83(major),21.13(major),21.11(minor),20.88(minor),14.13(major and minor)；HRMS(ESI-TOF)Calcd for C27H45N2O2 +([M+H]+)429.3476.Found 429.3477.
Figure BDA0001989255010000181
2e2, N- (2- (5-bromo-1-dodecanoyl-3-methylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to yield a 3:1 inseparable rotamer mixture, white solid: mp 97-98 ℃.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.42(stack,19H major and 19H minor),1.68-1.73(stack,2H major and 2H minor),1.77-1.90(stack,2H major and2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.51(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.92-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.20(d,J＝1.6Hz,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.71(major),171.39(minor),170.36(major),169.89(minor),141.46(major and minor),140.51(major),139.31(minor),131.39(minor),130.92(major),125.23(major and minor),118.69(minor),118.50(major),116.22(minor),115.92(major),60.39(minor),60.00(major),46.72(minor),44.00(major),42.61(major),42.35(minor),39.68(minor),38.21(major),36.31(major),36.03(minor),35.98(major),33.29(minor),31.90(major and minor),29.62,29.52,29.50,29.35,29.34,27.16(major),26.94(minor),24.50(minor),24.42(major),22.68(major and minor),21.81(major),20.95(minor),14.13(major and minor)；HRMS(ESI-TOF)Calcd for C26H42BrN2O2 +([M+H]+)493.2424.Found493.2414.
Figure BDA0001989255010000182
2f1, N- (2- (3, 5-dimethyl-1-octadecanoyl-3-yl) ethyl) -N-methylacetamide, hindered rotation of the DMA N- (CO) bond to give a 2:1 inseparable mixture of rotamers (the other two isomers were produced due to hindered rotation of the anilide N- (CO) and were obtained in small amounts and not characterized), white solid: mp 76-77 ℃.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.41(stack,31H major and 31H minor),1.69-1.96(stack,4H major and 7H minor),2.02(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.35-2.50(stack,2H major and 2H minor),2.84(s,3H minor),2.88(s,3H major),2.95-3.03(stack,1H major and 1H minor),3.15-3.24(m,1H minor),3.42-3.49(m,1H major),3.69(d,J＝10.4Hz,1H major),3.75(d,J＝10.4Hz,1H minor),3.86(d,J＝10.4Hz,1H minor),4.07(d,J＝10.4Hz,1H major),6.91(s,1H major),7.00(d,J＝7.9Hz,1H major,and brs(stack),1H minor),7.05(d,J＝8.1Hz,1H minor),8.09(d,J＝8.4Hz,1H major),8.12(d,J＝8.4Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.22(major),170.97(minor),170.25(major),169.94(minor),140.08(minor),140.03(major),138.18(major),137.00(minor),133.54(minor),133.17(major),128.94(minor),128.50(major),122.59(major),122.47(minor),116.92(minor),116.73(major),60.45(minor),60.18(major),46.86(minor),44.16(major),42.43(major),42.20(minor),39.88(minor),38.24(major),36.22(major),36.01(minor),35.96(major),33.23(minor),31.91(major and minor),29.68,29.64,29.53,29.52,29.41,29.35,27.14(major),27.06(minor),24.63(minor),24.57(major),22.68(major and minor),21.80(major),21.11(major),21.09(minor),20.86(minor),14.11(major and minor)；HRMS(ESI-TOF)Calcd for C33H57N2O2 +([M+H]+)513.4415.Found 513.4418.
Figure BDA0001989255010000191
2f2, N- (2- (5-bromo-3-methyl-1-octadecanoyl indolin-3-yl) ethyl) -N-methylacetyl, DMA N- (CO) bond rotation hindered to yield a 3:1 inseparable rotamer mixture, white solid: mp 70-71 ℃.1H NMR(400MHz,CDCl3)δ＝0.88(t,J＝7.0Hz,3H major and 3H minor),1.26-1.42(stack,31H major and 31H minor),1.68-1.77(stack,2H major and 2H minor),1.78-1.90(stack,2H major and2H minor),1.94(s,3H minor),2.02(s,3H major),2.35-2.50(stack,2H major and 2H minor),2.86(s,3H minor),2.90(s,3H major),2.94-3.07(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.43-3.50(m,1H major),3.71(d,J＝10.4Hz,1H major),3.78(d,J＝10.4Hz,1H minor),3.87(d,J＝10.4Hz,1H minor),4.13(d,J＝10.4Hz,1H major),7.20(d,J＝1.5Hz,1H major),7.22(s,1H minor),7.31(dd,J＝2.0,8.6Hz,1H major),7.36(dd,J＝2.0,8.6Hz,1H minor),8.11(d,J＝8.6Hz,1H major),8.14(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.72(major),171.39(minor),170.37(major),169.90(minor),141.46(major and minor),140.51(major),139.30(minor),131.40(minor),130.93(major),125.23(major and minor),118.70(minor),118.51(major),116.23(minor),115.92(major),60.40(minor),60.00(major),46.72(minor),44.01(major),42.61(major),42.35(minor),39.69(minor),38.22(major),36.31(major),36.04(minor),35.98(major),33.30(minor),31.93(major and minor),29.70,29.66,29.64,29.53,29.51,29.36,27.16(major),26.95(minor),24.50(minor),24.43(major),22.69(major and minor),21.81(major),20.95(minor),14.13(major and minor)；HRMS(ESI-TOF)Calcd for C32H54BrN2O2 +([M+H]+)577.3363.Found 577.3376.
Figure BDA0001989255010000192
2g of N- (2- (3, 5-dimethyl-1-pivaloylindolin-3-yl) ethyl) -N-methylacetamide, hindered rotation of the DMA N- (CO) bond to give a 2:1 inseparable mixture of rotamers (the other two isomers were produced in small amounts, uncharacterized, due to hindered rotation of the anilide N- (CO)), pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.36(s,3H major),1.378(s,9H minor),1.381(s,9H major),1.40(s,3H minor),1.74-1.94(stack,2H major and 5H minor),2.03(s,3H major),2.32(s,3H major),2.33(s,3H minor),2.83(s,3H minor),2.87(s,3H major),3.01-3.13(stack,1H major and 1H minor),3.17-3.25(m,1H minor),3.41-3.49(m,1H major),3.86(d,J＝10.3Hz,1H major),3.87(d,J＝10.3Hz,1H minor),4.09(d,J＝10.3Hz,1H minor),4.21(d,J＝10.3Hz,1H major),6.91(s,1H major and 1H minor),7.01(dd,J＝1.0,8.3Hz,1H major),7.05(d,J＝8.4Hz,1H minor),8.09(d,J＝8.2Hz,1H major),8.11(d,J＝8.2Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝176.28(major),175.98(minor),170.32(major),170.01(minor),141.62(minor),141.55(major),137.92(major),136.65(minor),133.75(minor),133.44(major),128.83(minor),128.40(major),122.40(major),122.29(minor),118.42(minor),118.23(major),61.81(minor),61.51(major),46.89(minor),44.11(major),43.12(major),42.87(minor),40.11(major and minor),39.16(minor),37.37(major),36.15(major),33.29(minor),27.70(major),27.66(minor),25.62(major),25.53(minor),21.86(major),21.10(major),21.09(minor),20.91(minor)；HRMS(ESI-TOF)Calcd for C20H31N2O2 +([M+H]+)331.2380.Found331.2380.
Figure BDA0001989255010000201
2h1, 5-chloro-3-methyl-3- (2- (N-methylacetamido) ethyl) indoline-1-carboxylic acid tert-butyl ester, hindered in rotation by the DMA N- (CO) bond to give a 15:8 inseparable mixture of rotamers as a pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.34(s,3H major),1.38(s,3H minor),1.56(s,9H major and 9H minor),1.76-1.93(stack,2H major and 2H minor),1.96(s,3H minor),2.03(s,3H major),2.86(s,3H minor),2.90(s,3H major),2.95-3.11(stack,1H major and 1H minor),3.19-3.27(m,1H minor),3.45-3.52(m,1H major),3.63-3.70(stack,1H major and 1H minor),3.83(d,J＝7.9Hz,1H minor),3.93(d,J＝11.3Hz,1H major),7.04(d,J＝2.0Hz,1H major and 1H minor),7.13(dd,J＝1.6,8.5Hz,1H major),7.17(dd,J＝1.7,8.6Hz,1H minor),7.36(brs,unexchengeable,1H minor),7.76(brs,unexchengeable,1H major)；13C{1H}NMR(100MHz,CDCl3)δ＝170.34(major),169.99(minor),152.30(major),152.13(br,minor),140.78(br),139.88(br),138.73(br,minor),128.22(minor),127.80(major),127.60(minor),127.27(major),122.53(br,major and minor),115.93(minor),115.71(major),82.08(br,minor),81.11(br,major),59.72(major and minor),46.77(minor),44.03(major),41.80(br,major and minor),39.72(minor),37.74(major),36.22(major),33.27(minor),28.41(major and minor),27.24(br,major),26.99(minor),21.86(major),20.95(minor)；HRMS(ESI-TOF)Calcd for C19H28ClN2O3 +([M+H]+)367.1783.Found 367.1784.
Figure BDA0001989255010000211
2h2, N- (2- (5-chloro-1- (ethylsulfonyl) -3-methylindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to give a 5:2 inseparable rotamer mixture as a slightly yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.37(s,3H major),1.39-1.44(stack,3H major and 6H minor),1.79-1.93(stack,2H major and 2H minor),1.97(s,3H minor),2.02(s,3H major),2.86(s,3H minor),2.94(s,3H major),2.98-3.07(m,1H minor),3.11-3.42(stack,4H major and 3H minor),3.70(d,J＝10.2Hz,1H major and 1H minor),3.93(d,J＝10.2Hz,1H minor),4.01(d,J＝10.2Hz,1H major),7.08(d,J＝2.0Hz,1H major),7.09(d,J＝2.0Hz,1H minor),7.14(dd,J＝2.1,8.6Hz,1H major),7.20(dd,J＝2.1,8.6Hz,1H minor),7.29(d,J＝8.6Hz,1H major),7.30(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.44(major),170.01(minor),140.06(major and minor),139.98(major),138.93(minor),128.77(minor),128.71(minor),128.34(major),128.23(major),123.40(major),123.24(minor),114.38(minor),114.21(major),61.81(minor),61.55(major),46.60(minor),44.51(minor),44.35(major),43.90(major),42.72(major),42.43(minor),39.33(minor),37.04(major),36.25(major),33.30(minor),26.38(major),26.28(minor),21.81(major),20.99(minor),7.75(major and minor)；HRMS(ESI-TOF)Calcd for C16H24ClN2O3S+([M+H]+)359.1191.Found 359.1192.
Figure BDA0001989255010000212
2j, N- (2- (1-acetyl-4-chloro-3-methylindolin-3-yl) ethyl) -N-methylDimethylacetamide, hindered rotation of the DMA N- (CO) bond to give a 5:2 inseparable mixture of rotamers as a pale yellow liquid.1H NMR(400MHz,CDCl3)δ＝1.51(s,3H major),1.57(s,3H minor),1.82-1.91(m,1H major),2.00(s,3H minor),2.03(s,3H major),2.25(s,3H minor),2.26(s,3H major),2.32-2.49(stack,1H major and 2H minor),2.60-2.68(m,1H major),2.89(s,3H minor),2.95(s,3H major),2.97-3.05(m,1H minor),3.10-3.18(m,1H minor),3.66(dd,J＝4.4,12.8Hz,1H major),3.72(d,J＝10.6Hz,1H major),3.81(d,J＝10.4Hz,1H minor),3.90(d,J＝10.4Hz,1H minor),4.24(d,J＝10.5Hz,1H major),6.97(d,J＝8.0Hz,1H major),7.02(d,J＝8.0Hz,1H minor),7.15(dd,J＝8.1,8.1Hz,1H major),7.19(dd,J＝8.1,8.1Hz,1H minor),8.18(d,J＝8.1Hz,1H major),8.20(d,J＝8.1Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.39(major),170.14(minor),169.12(major),168.69(minor),144.37(major),144.28(minor),132.86(major),131.92(minor),129.99(minor),129.92(minor),129.87(major),129.56(major),125.38(minor),125.04(major),115.76(minor),115.64(major),61.24(minor),60.96(major),47.19(minor),44.36(major),44.08(major),43.86(minor),36.75(minor),36.41(major),35.26(major),33.32(minor),26.60(minor),26.36(major),24.42(major and minor),21.76(major),20.96(minor)；HRMS(ESI-TOF)Calcd for C16H22ClN2O2 +([M+H]+)309.1364.Found309.1372.
Figure BDA0001989255010000221
2k, N- (2- (1-acetyl-5-bromoindolin-3-yl) ethyl) -N-methylacetamide, DMA N- (CO) bond rotation hindered to produce a 4:1 inseparable mixture of rotamers (the other two isomers were produced due to anilide N- (CO) rotation hindered, with low availability, uncharacterized), white semi-solid.1H NMR(400MHz,CDCl3)δ＝1.66-1.75(m,1H major),1.81-1.92(m,1H minor),1.97-2.07(stack,1H major and 1H minor),2.08(s,3H minor),2.10(s,3H major),2.23(s,3H major and 3H minor),2.94(s,3H minor),3.02(s,3H major),3.19-3.44(stack,2H major and 3H minor),3.68-3.76(stack,1H major and 1H minor),3.83(dd,J＝6.0,10.6Hz,1H major),4.19-4.26(stack,1H major and 1H minor),7.27(s,1H major and 1H minor),7.30(dd,J＝1.5,8.6Hz,1H major),7.35(dd,J＝1.6,8.6Hz,1H minor),8.08(d,J＝8.6Hz,1H major),8.11(d,J＝8.6Hz,1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝170.82(major),170.01(minor),168.91(major),168.57(minor),141.86(major),141.71(minor),136.80(major),135.70(minor),131.26(minor),130.79(major),126.67(major and minor),118.53(minor),118.35(major),116.14(minor),115.89(major),54.95(major),54.76(minor),48.23(minor),44.76(major),37.65(minor),37.50(major),36.02(major),33.73(minor),33.37(minor),32.71(major),24.19(major and minor),21.85(major),21.20(minor)；HRMS(ESI-TOF)Calcd for C15H20BrN2O2 +([M+H]+)339.0703.Found 339.0702.
Figure BDA0001989255010000222
2l of N- (2- (3, 5-dimethyl-1-octanoylindolin-3-yl) ethyl) -N-methylformamide, hindered rotation of the DMA N- (CO) bond to give a 3:2 inseparable mixture of rotamers (the other two isomers were produced as a result of hindered rotation of the anilide N- (CO), were obtained in small amounts and were not characterized), a yellowish liquid.1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝6.8Hz,3H major and 3H minor),1.29-1.40(stack,11H major and 11H minor),1.69-1.77(stack,2H major and 2H minor),1.80-1.95(stack,2H major and 2H minor),2.326(s,3H major),2.334(s,3H minor),2.36-2.50(stack,2H major and 2H minor),2.80(s,3H minor),2.85(s,3H major),2.96-3.04(stack,1H major and 1H minor),3.14-3.22(m,1H minor),3.37-3.44(m,1H major),3.70-3.76(stack,1H major and 1H minor),3.86(d,J＝10.4Hz,1H minor),4.04(d,J＝10.5Hz,1H major),6.89(s,1H minor),6.92(s,1H major),7.01-7.06(stack,1H major and 1H minor),7.91(s,1H minor),7.96(s,1H major),8.09-8.12(stack,1H major and1H minor)；13C{1H}NMR(100MHz,CDCl3)δ＝171.27,171.05,162.34,162.30,140.07,140.02,137.86,136.98,133.63,133.34,129.01,128.70,122.62,122.57,116.96,116.83,60.55,60.35,45.81,42.48,42.33,40.79,40.09,37.86,36.03,36.01,34.58,31.74,31.73,29.66,29.38,29.18,29.16,27.18,26.93,24.62,24.60,22.64,21.14,14.10,14.09；HRMS(ESI-TOF)Calcd for C22H35N2O2 +([M+H]+)359.2693.Found 359.2691.
Figure BDA0001989255010000231
2m,5- ((3, 5-dimethyl-1-octanoylindolin-3-yl) methyl) -1-methylpyrrolidin-2-one, 1:1 diastereomer mixture and 5:1 rotamer mixture, yellowish liquid.1H NMR(400MHz,CDCl3)δ＝0.89(t,J＝6.9Hz,6H),1.18-1.44(stack,24H),1.54-1.75(stack,8H),2.02-2.30(stack,6H),2.33(s,6H),2.37-2.42(stack,4H),2.68(s,3H),2.73(s,3H),3.24-3.30(m,1H),3.41-3.47(m,1H),3.76(dd,J＝10.4,13.3Hz,2H),3.92(d,J＝9.5Hz,2H),6.92(d,J＝9.6Hz,2H),7.05(d,J＝8.3Hz,2H),8.11(dd,J＝1.7,8.2Hz,2H)；13C{1H}NMR(100MHz,CDCl3)δ＝174.82,174.48,171.04,170.91,140.13,140.09,137.54,137.38,133.60,133.39,129.01,128.93,123.15,122.65,117.00,116.95,61.14,60.78,57.47,45.45,44.59,42.57,42.28,36.07,35.99,31.71,29.95,29.73,29.38,29.15,27.78,27.71,27.52,27.25,26.97,26.11,24.63,24.59,22.62,21.13,14.09；HRMS(ESI-TOF)Calcd for C24H37N2O2 +([M+H]+)385.2850.Found385.2854.
Figure BDA0001989255010000232
2N, N- (2- (1-acetyl-3-methylindolin-3-yl) ethyl) acetamide, a mixture of rotamers 6:1, white solid mp 130-.1H NMR(400MHz,CDCl3)δ＝1.39(s,3H),1.80-1.93(m,5H),2.24(s,3H),2.95-3.04(m,1H),3.22-3.36(m,1H),3.74(d,J＝10.4Hz,1H),4.01(d,J＝10.4Hz,1H),5.30(brs,1H),7.06(dd,J＝7.4,7.4Hz,1H),7.12(d,J＝7.4Hz,1H),7.23(dd,J＝7.4,8.4Hz,1H),8.20(d,J＝8.1Hz,1H)；13C{1H}NMR(100MHz,CDCl3)δ＝170.09,168.80,142.04,138.09,128.20,123.92,122.31,117.08,61.03,42.64,41.06,35.99,27.07,24.32,23.21；HRMS(ESI-TOF)Calcd for C15H21N2O2 +([M+H]+)261.1598.Found 261.1591。

Claims (2)

1. A synthetic method of a2, 3-dihydrotryptamine compound, wherein the 2, 3-dihydrotryptamine compound has a compound structure shown in a formula II, and is characterized in that the reaction route is as follows:
Figure FDA0003555238650000011
the catalyst is DCP, the dosage of DCP is 2-3 equivalent; the solvent used in the reaction is a mixed water phase solvent formed by DMA and water, wherein the volume ratio of DMA to water is 3-5: 1; the reaction temperature is 115-125 ℃.
2. A synthetic method of a2, 3-dihydrotryptamine compound is characterized in that the reaction route is as follows:
Figure FDA0003555238650000012
wherein:
R1is methyl, R2Is 4-methyl, R3Is COR7，R6Is methyl, R7Is n-C7H15；
The catalyst is DCP, the dosage of the DCP is 3 equivalents; the solvent used in the reaction is a mixed water phase solvent formed by 1-methylpyrrolidine-2-ketone and water, wherein the volume ratio of the 1-methylpyrrolidine-2-ketone to the water is 5: 1; the reaction temperature was 120 ℃.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1118451C (en) * 1995-08-08 2003-08-20 西玛夫公司 Acylated derivatives of melatonin and its analogues, useful as medicaments
WO2005084664A1 (en) * 2004-03-08 2005-09-15 Kanazawa University Technology Licensing Organization Ltd. Indole derivatives and uses thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10112882A1 (en) * 2001-03-15 2002-09-19 Max Delbrueck Centrum Selective cytostatic treatment of serotonin-producing tumors, using non-toxic tryptophan derivatives, e.g. 7-hydroxytryptophan, which are enzymatically converted into specific toxins in the tumor cells
CN108264474B (en) * 2018-02-09 2019-10-25 浙江师范大学 A kind of synthetic method of tryptamines and its derivative
CN109232316B (en) * 2018-11-13 2021-03-26 昆明学院 Synthetic method of alpha-tertiary nitrile structure beta-dicarbonyl compound

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1118451C (en) * 1995-08-08 2003-08-20 西玛夫公司 Acylated derivatives of melatonin and its analogues, useful as medicaments
WO2005084664A1 (en) * 2004-03-08 2005-09-15 Kanazawa University Technology Licensing Organization Ltd. Indole derivatives and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Transition-Metal-Free Amidoalkylation of Benzothiazoles and Amidoalkylarylation of Activated Alkenes with N,N-Dialkylamides;Jian Wang et,al.;《The Journal of Organic Chemistry》;20160314;第1-14页 *

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