CN113912529B - Method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate with ruthenium - Google Patents

Method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate with ruthenium Download PDF

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CN113912529B
CN113912529B CN202111070628.5A CN202111070628A CN113912529B CN 113912529 B CN113912529 B CN 113912529B CN 202111070628 A CN202111070628 A CN 202111070628A CN 113912529 B CN113912529 B CN 113912529B
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vinylene carbonate
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CN113912529A (en
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李喆宇
赵欢
于瑶
谭玉强
王洋
程泽民
孙雅楠
辜玲慧
马文博
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Chengdu University
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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
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D209/56—Ring systems containing three or more rings
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    • C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
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Abstract

The invention discloses a method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate by ruthenium, which comprises the steps of firstly mixing an N-aryl amide substrate, vinylene carbonate, a ruthenium catalyst, a first additive and a second additive, then adding an organic solvent under the protection of inert gas, and uniformly stirring and reacting for a period of time to obtain a primary product; and then sequentially extracting and carrying out column chromatography treatment on the initial product to obtain the indole compound. The invention provides a novel method for synthesizing indole compounds, which is simple in operation, economical and environment-friendly, and mild in reaction condition, effectively solves the problems of harsh reaction condition, complex operation, limited substrate, complicated steps, intolerance of functional groups of the substrate and the like in the prior art, and opens up a new path for synthesizing indole compounds.

Description

Method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate with ruthenium
Technical Field
The invention belongs to the technical field of indole compound synthesis, and particularly relates to a method for synthesizing an indole compound by catalyzing N-aryl amide compound and vinylene carbonate through ruthenium.
Background
Indole is a common synthetic raw material for drug molecules or dyes, and its synthetic method has been the focus of attention of chemists. The traditional indole synthesis method adopts phenylhydrazine and ketone or aldehyde to carry out intermolecular cyclization reaction to prepare the indole. In recent years, most of indole synthesis methods adopt o-alkynylaniline with pre-functional groups as a substrate and synthesize indole through intramolecular cyclization, but the reaction route is longer, the reaction conditions are harsh, the functional group tolerance is poor, and the diversity of products is greatly limited. Therefore, it is necessary to explore a new synthesis method with mild reaction conditions, better substrate tolerance and shorter reaction steps.
In recent years, transition metal catalyzed selective C-H functionalization has become an important strategy for bioactive molecule synthesis or structural modification. However, studies on transition metal catalyzed synthesis of indole compounds have mostly employed transition metal catalyzed cyclization of aryl amides with acetylenic substrates. The reaction uses expensive alkyne as a coupling reagent, and the 2-position or 3-position of the synthesized indole compound contains substituent groups, so that the diversity of products is greatly limited. Based on this, the prior art publication reports rhodium catalyzed cyclization of N-aryl amides with vinylene carbonate. Although the reaction provides an economic and convenient synthetic route for indole compounds, the reaction involves a rhodium catalyst which is expensive, and the reaction temperature is as high as 140 ℃ to limit the diversity of products, so that the development of an inexpensive ruthenium metal catalyst has important significance in carrying out a reaction method for efficiently and conveniently synthesizing indole derivatives under mild conditions, and lays a foundation for the development of medicaments.
Disclosure of Invention
Aiming at the prior art, the invention provides a method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate by ruthenium, so as to provide a novel indole compound synthesis method.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: the method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate with ruthenium is provided, and the reaction equation is as follows:
the synthesis method comprises the following steps:
s1: mixing an N-aryl amide substrate, vinylene carbonate, a ruthenium catalyst, a first additive and a second additive, adding an organic solvent under the protection of inert gas, uniformly stirring, and reacting for 20-30 h at 75-85 ℃ to obtain a primary product;
s2: sequentially extracting and performing column chromatography treatment on the initial product to obtain indole compounds.
On the basis of the technical scheme, the invention can be improved as follows.
Further, the molar ratio of the N-aryl amide substrate to the vinylene carbonate is 1:3-5.
Further, the organic solvent is ethylene glycol dimethyl ether.
Further, the addition amounts of the ruthenium catalyst, the oxidant and the additive are 4 to 7%, 18 to 22% and 8 to 12% of the total molar amounts of the N-aryl amide substrate and the vinylene carbonate, respectively.
Further, the ruthenium catalyst is [ RuCl ] 2 (p-cymene)] 2 。
Further, the first additive is AgSbF 6 。
Further, the second additive is Zn (OAc) 2 。
Further, the reaction temperature in S1 was 80℃and the reaction time was 24 hours.
Further, the extraction method in S2 is as follows: adding a mixed solution of water and ethyl acetate into the initial product, uniformly stirring, standing until complete layering, and then separating an organic layer and a water layer; repeating the above operation twice, drying and concentrating the organic layer to complete the extraction of the primary product; the volume ratio of water to ethyl acetate in the mixed solution of water and ethyl acetate is 1-2:1.
Further, the column used in the column chromatography treatment in the S2 is a silica gel column, and the chromatographic solution is a mixed solution of petroleum ether and ethyl acetate according to the volume ratio of 50:1-10:1.
The beneficial effects of the invention are as follows: the invention provides an indole compound prepared by a selective cyclization reaction of an N-aryl amide compound, which is simple to operate and easy to obtain raw materials. The transition metal ruthenium is used as a catalyst and has low price. The reaction byproducts are only carbon dioxide and water, so that the method is environment-friendly. The reaction condition is mild, the derivative range is wide, and the structural diversity of indole compounds is enriched. The synthesis method solves the problems of harsh reaction conditions, complex operation, limited substrate, complex steps, intolerance of the functional groups of the substrate and the like in the traditional method, and opens up a new path for synthesizing indole compounds.
Drawings
FIG. 1 is a diagram showing the mechanism of synthesis of indole compounds according to the present invention.
Detailed Description
The following describes the present invention in detail with reference to examples.
Example 1
The reaction tube was charged with: 0.20mmol of N-arylamide substrate shown in Table 1, 0.8mmol of vinylene carbonate, 0.010mmol of RuCl 2 (p-cymene)] 2 ，0.02mmol Zn(OAc) 2 And 0.04mmol AgSbF 6 Dry ethylene glycol dimethyl ether (2 mL) was added under argon protection, and the reaction tube was filled with argon, and then reacted at 80 ℃ for 24 hours to obtain the initial product.
Adding water and ethyl acetate (volume ratio of 1:1) into the initial product after the reaction is finished, extracting for three times, combining organic layers, and anhydrous Na 2 SO 4 The organic layer was dried, filtered, concentrated, and purified by silica gel column chromatography (petroleum ether/ethyl acetate=50/1-25/1) to give the product.
TABLE 1N aryl amide substrates
The final product structure and corresponding spectrogram data are as follows:
N-tert-butyryl-1H indole (1- (1H-indol-1-yl) -2, 2-dimethylpropan-1-one) (3 a) was prepared starting from N-tert-butylacetanilide (1 a) (35.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). By column chromatography (Petroleum ether/ethyl acetate: 50/1 →25/1) to give 3a (The general procedure was followed by using N-phenylpivalamide (1 a) (35.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) as a white solid Purification by column chromatography (Petroleum ether/EtOAc: 50/1.fwdarw.25/1) yielded 3a as a white solid.) (35.7 mg, 89%) M.p =65-68 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.55(d,J＝8.5Hz,1H),7.74(d,J＝3.9Hz,1H),7.57(d,J＝7.7Hz,1H),7.36(dd,J＝7.3,7.8Hz,1H),7.28(d,J＝7.3,7.8Hz,1H),6.63(d,J＝3.9Hz,1H),1.53(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.3,137.0,129.6,125.9,125.3,123.8,120.7,117.6,108.5,41.4,28.9.HR-MS(ESI)m/z calcd for:C 13 H 16 NO + [M+H + ]202.1226,found 202.1227.
N-formyl-1H indole (3 b) (1- (1H-indol-1-yl) ethan-1-one) was prepared starting from N-methylacetanilide (1 b) (27.0 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 50/1. Fwdarw.20/1) afforded 3b (17.2 mg, 54%) as a yellow oil (The general procedure was followed by using N-phenacetamide (1 b) (27.0 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum ether/EtOAc: 50/1. Fwdarw.20/1) yielded 3b (17.2 mg, 54%) as a yellow oil. 1 H NMR(600MHz,CDCl 3 )δ＝8.44(d,J＝7.2Hz,1H),7.56(d,J＝7.8Hz,1H),7.41(d,J＝3.8Hz,1H),7.36–7.33(m,1H),7.28–7.26(m,1H),6.63(d,J＝3.8Hz,1H),2.63(s,3H). 13 C NMR(150MHz,CDCl 3 )δ＝168.7,135.6,130.5,125.3,125.1 123.8,120.9,116.6,109.3,24.1.HR-MS(ESI)m/z calcd for:C 10 H 10 NO + [M+H + ]160.0757,found 160.0758.
N-acetyl-1H indole (3 c) (1- (1H-indol-1-yl) pro-pan-1-one) was prepared starting from N-ethylacetanilide (1 c) (29.8 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/Ethyl acetate: 70/1. Fwdarw.30/1) afforded yellow solid 3c (24.9 mg, 72%) (The general procedure was followed by using N-phenylpropionamide (1 c) (29.8 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 70/1. Fwdarw.30/1) yielded 3c (24.9 mg, 72%) as a yellow solid) M.p =59-63 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.47(d,J＝8.2Hz,1H),7.56(d,J＝7.8Hz,1H),7.45(d,J＝3.7Hz,1H),7.36–7.33(m,1H),7.27(d,J＝7.8Hz,1H),6.63(d,J＝3.7Hz,1H),2.94(q,J＝7.4Hz,2H),1.34(t,J＝7.4Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ＝172.3,135.7,130.4,125.2,124.6,123.6,120.9,116.7,109.1,29.3,8.8.HR-MS(ESI)m/z calcd for:C 11 H 12 NO + [M+H + ]174.0913,found 174.0914.
N-phenyl-1H-indole-1-carboxamide (3 d) (N-phenyl-1H-indole-1-carboxamide) was prepared starting from 1,3-diphenylurea (1 d) (42.3 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/EtOAc: 50/1. Fwdarw.15/1) afforded 3d (16.5 mg, 35%) (The general procedure was followed by using 1, 3-diphenyourea (1 d) (42.3 mg,0.20 mmol) and 1, 3-dioxanol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 50/1. Fwdarw.15/1) yielded 3d (16.5 mg, 35%) as orange oil. 1 H NMR(600MHz,CDCl 3 )δ＝8.10(d,J＝8.3Hz,1H),7.62(d,J＝7.8Hz,1H),7.54(d,J＝3.6Hz,1H),7.52–7.51(m,2H),7.43(s,1H),7.39–7.36(m,2H),7.36–7.33(m,1H),7.27–7.24(m,1H),7.18–7.16(m,1H),6.66(d,J＝3.6Hz,1H). 13 C NMR(150MHz,CDCl 3 )δ＝149.7,137.1,135.2,130.5,129.4,124.9,124.6,124.2,122.8,121.5,120.6,114.1,107.8.HR-MS(ESI)m/z calcd for:C 15 H 13 N 2 O + [M+H + ]237.1022,found 237.1022.
N, N-dimethyl-1H-indole-1-carboxamide (3 e) (N, N-dimethyl-1H-indole-1-carboxamide) was prepared starting from 1,1-dimethyl-3-phenylurea (1 e) (32.8 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 25/1. Fwdarw.5/1) afforded 3e (17.7 mg, 47%) as a yellow oil (The general procedure was followed by using 1,1-dimethyl-3-phenylurea (1 e) (32.8 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 25/1. Fwdarw.5/1) yielded 3e (17.7 mg, 47%) as an orange oil. 1 H NMR(600MHz,CDCl 3 )δ＝7.64(d,J＝8.3Hz,1H),7.59(d,J＝7.8Hz,1H),7.31(d,J＝3.5Hz,1H),7.30–7.27(m,1H),7.20–7.17(m,1H),6.59(d,J＝3.5Hz,1H),3.08(s,6H). 13 C NMR(150MHz,CDCl 3 )δ＝155.2,135.5,129.5,126.3,123.6,121.8,121.1,113.5,105.8,38.5.HR-MS(ESI)m/z calcd for:C 11 H 13 N 2 O + [M+H + ]189.1022,found 189.1023.
5-methyl-N-tert-butylacyl-1H-indole (3 f) (2, 2-dimethyl-1- (5-methyl-1H-indol-1-yl) pro an-1-one):
n- (p-methylphenyl) t-butyramide (1 f) (38.3 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared as starting materials. Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded 3f (36.8 mg, 85%) as a white solid (The general procedure was followed by using N- (p-tolyl) pivalamide (1 f) (38.3 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3f(36.8mg,85％)as a white solid).M.p＝61–64℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.40(d,J＝8.5Hz,1H),7.69(d,J＝3.7Hz,1H),7.35(s,1H),7.17(d,J＝8.5Hz,1H),6.55(d,J＝3.7Hz,1H),2.45(s,3H),1.51(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,135.1,133.2,129.7,126.5,125.8,120.5,117.1,108.2,41.3,28.8,21.4.HR-MS(ESI)m/z calcd for:C 14 H 18 NO + [M+H + ]216.1383,found 216.1382.
5-tert-butyl-N-tert-butyryl-1H-indole (3 g)
6- (1- (5- (tert-butyl) -1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4- (tert-butyl) phenyl) tert-butyramide (1 g) (46.7 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). 3g (36.8 mg, 84%) of (The general procedure was followed by using N- (4- (tert-butyl) phenyl) pivalamide (1 g) (46.7 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3g (36.8 mg, 84%) as a white solid was isolated and purified by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1). 1 H NMR(600MHz,,CDCl 3 )δ＝8.46(d,J＝8.8Hz,1H),7.71(d,J＝3.7Hz,1H),7.58(s,1H),7.44(d,J＝8.8Hz,1H),6.61(d,J＝3.7Hz,1H),1.52(s,9H),1.40(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,146.8,134.9,129.4,125.8,123.1,116.9,116.8,108.6,41.2,34.8,31.8,28.8.HR-MS(ESI)m/z calcd for:C 17 H 24 NO + [M+H + ]258.1852,found 258.1850.
5-hexyl-N-tert-butyryl-1H-indole (3H) (1- (5-hexyl-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) N- (4-hexanylphenyl) tert-butyramide (1H) (52).2mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared as starting materials. Purification by column chromatography (Petroleum/EtOAc: 50/1. Fwdarw.30/1) afforded a brown oil of 3h (33 mg, 59%) (The general procedure was followed by using N- (4-hexyphenyl) pivalamide (1 h) (52.2 mg,0.2 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum/EtOAc: 50/1. Fwdarw.30/1) yielded 3h (33 mg, 59%) as brown oil). 1 H NMR(600MHz,CDCl 3 ) 1 H NMR(600MHz)δ＝8.41(d,J＝8.6Hz,1H),7.69(d,J＝3.8Hz,1H),7.34(d,J＝1.5Hz,1H),7.18(dd,J＝8.6,1.5Hz,1H),6.56(d,J＝3.8Hz,1H),2.73–2.66(m,2H),1.68–1.60(2H),1.51(s,9H),1.37–1.32(m,2H),1.32–1.24(m,4H),0.87(q,J＝7.0Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,138.4,135.2,129.6,126.0,125.8,119.9,117.1,108.2,41.2,35.9,32.0,31.9,29.1,28.8,22.7,14.2.HR-MS(ESI)m/z calcd for:C 19 H 28 NO + [M+H + ]286.2165,found 286.2166.
5-dodecyl-N-t-butyryl-1H-indole (3 i) (1- (5-dodecyl-1H-indol-1-yl) -2,2-dimethylprop an-1-one) prepared starting from N- (4-dodecylphenyl) t-butyramide (1 i) (69.2 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum/EtOAc: 50/1. Fwdarw.30/1) afforded 3i (40 mg, 55%) (The general procedure was followed by using N- (4-dodecyphenyl) pivalamide (1 i) (69.2 mg,0.2 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum/EtOAc: 50/1. Fwdarw.30/1) yielded 3i (40 mg, 55%) as brown oil. 1 H NMR(600MHz,CDCl 3 )δ＝8.40(d,J＝8.6Hz,1H),7.69(d,J＝3.7Hz,1H),7.34(d,J＝1.6Hz,1H),7.17(dd,J＝8.6,1.6Hz,1H),6.55(d,J＝3.7Hz,1H),2.70–2.67(m,2H),1.67–1.60(m,2H),1.50(s,9H),1.36–1.30(m,4H),1.28–1.22(m,14H),0.87(t,J＝7.1Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,138.4,135.2,129.6,126.0,125.7,119.9,117.1,108.2,41.2,35.9,32.1,32.0,30.0,29.8,29.7,29.7,29.5,29.4,28.8,22.8,14.2.HR-MS(ESI)m/zcalcd for:C 25 H 40 NO + [M+H + ]370.3104,found 370.3105.
5-methoxy-N-tert-butyryl-1H-indole (3 j) (1- (5-methoxy-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4-methoxyphenyl) tert-butyramide (1 j) (41.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). The white solid 3j (43 mg, 92%) (The general procedure was followed by using N- (4-methoxyphenyl) pivalamide (1 j) (41.5 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc:50/1→10/1) yielded 3j (43 mg, 92%) as a white solid M.p =92-95℃ was isolated and purified by column chromatography (Petroleum ether/ethyl acetate: 50/1→10/1:25→5/1). 1 H NMR(600MHz,CDCl 3 )δ＝8.41(d,J＝9.1Hz,1H),7.70(d,J＝3.8Hz,1H),7.01(d,J＝2.4Hz,1H),6.95(dd,J＝9.1,2.4Hz,1H),6.54(d,J＝3.8Hz,1H),3.84(s,3H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝176.8,156.5,131.6,130.4,126.4,118.2,113.5,108.2,103.4,55.7,41.2,28.9.HR-MS(ESI)m/z calcd for:C 14 H 18 NO 2 + [M+H + ]232.1332,found 232.1331.
5-benzyloxy-N-tert-butyryl-1H-indole (3 k)
(1- (5- (Benzyloxy) -1H-indol-1-yl) -2, 2-dimethylpropan-1-one) N- (4- (benzyloxy) phenyl) tert-butyramide (1 k) (57 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared as raw materials. Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 20/1) gave 3k (52 mg, 84%) as a yellow oil (The general procedure was followed by using)N-(4-(benzyloxy)phenyl)pivalamide(1k)(57mg,0.2mmol)and 1,3-dioxol-2-one(2)(68.8mg,0.8mmol).Purification by column chromatography(Petroleum/EtOAc:20/1)yielded 3k(52mg,84％)as a brown oil). 1 H NMR(600MHz) 1 H NMR(600MHz,CDCl 3 )δ＝8.41(d,J＝9.0Hz,1H),7.70(d,J＝3.9Hz,1H),7.46(d,J＝7.3Hz,2H),7.39–7.37(m,2H),7.33–7.30(m,1H),7.08(d,J＝2.7Hz,1H),7.03(dd,J＝9.0,2.7Hz,1H),6.53(d,J＝3.8Hz,1H),5.11(s,2H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝176.8,155.6,137.4,131.7,130.4,128.6,127.9,127.5,126.4,118.2,114.3,108.2,104.8,70.6,41.2,28.8.HR-MS(ESI)m/z calcd for:C 20 H 22 NO 2 + [M+H + ]308.1645,found 308.1650.
5-phenoxy-N-tert-butyryl-1H-indole (3 l) (2, 2-dimethyl-1- (5-phenoxy-1H-indol-1-yl) pro-pan-1-one) was prepared starting from N- (4-phenoxyphenyl) tert-butyramide (1 l) (53.8 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum/EtOAc: 40/1. Fwdarw.20/1) afforded 3l (33 mg, 57%) of (The general procedure was followed by using N- (4-phenolphenyl) pivalamide (1 l) (53.8 mg,0.2 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum/EtOAc: 40/1. Fwdarw.20/1) yielded 3l (33 mg, 57%) as brown oil. 1 H NMR(600MHz,CDCl 3 )δ＝8.49(d,J＝9.0Hz,1H),7.75(d,J＝3.9Hz,1H),7.34–7.27(m,2H),7.18(d,J＝2.5Hz,1H),7.09–7.04(m,2H),7.00–6.95(m,2H),6.55(d,J＝3.8Hz,1H),1.52(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,158.4,153.2,133.3,130.6,129.7,126.7,122.8,118.5,118.2,117.6,110.7,108.2,41.3,28.8.HR-MS(ESI)m/z calcd for:C 19 H 20 NO 2 + [M+H + ]294.1489,found 294.1491.
5-tert-butyryloxy-N-tert-butyryl-1H-indole (3 m) (1-pivaloyl-1H-indol-5-yl pivalate) 4-pentanoic acid tert-butyrylaminophenyl ester (1 m) (55.4 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared as raw materials. The white solid was isolated and purified by column chromatography (Petroleum ether/ethyl acetate: 20/1. Fwdarw.10/1) to give 3m (30 mg, 72%) (The general procedure was followed by using 4-pivalamidophenyl pivalate (1 m) (55.4 mg,0.2 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum/EtOAc: 20/1. Fwdarw.10/1) yielded 3m (30 mg, 72%) as a white solid). M.p =76-78 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.49(d,J＝9.0Hz,1H),7.75(d,J＝3.7Hz,1H),7.23(d,J＝2.4Hz,1H),7.01(dd,J＝9.0,2.4Hz,1H),6.57(d,J＝3.7Hz,1H),1.51(s,9H),1.37(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.6,177.0,147.3,134.5,130.1,126.8,118.7,118.0,112.9,108.2,41.3,39.2,28.8,27.3.HR-MS(ESI)m/z calcd for:C 18 H 24 NO 3 + [M+H + ]302.1751,found 302.1749.
5-methylsulfanyl-N-tert-butyryl-1H-indole (3N) (2, 2-dimethyl-1- (5- (methylsulfio) -1H-indol-1-yl) pro-pan-1-one) was prepared starting from N- (4- (methylsulfanyl) phenyl) tert-butyramide (1N) (44.7 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum/Ethyl acetate: 70/1. Fwdarw.30/1) afforded 3n (24.9 mg, 50%) as a yellow oil (The general procedure was followed by using N- (4- (methylhio) phenyl) pivalamide (1 n) (44.7 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 70/1. Fwdarw.30/1) yielded 3n (24.9 mg, 50%) as a yellow oil. 1 H NMR(600MHz,CDCl 3 )δ＝8.43(d,J＝8.8Hz,1H),7.72(d,J＝3.8Hz,1H),7.48(d,J＝1.8Hz,1H),7.30(dd,J＝8.8,1.8Hz,1H),6.55(d,J＝3.8Hz,1H),2.52(s,3H),1.51(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,135.1,132.9,130.3,126.4,125.4,119.5,117.8,107.8,41.3,28.8,17.4.HR-MS(ESI)m/z calcd for:C 14 H 16 NOS — [M-H + ]246.0958,found 246.0957.
5-fluoro-N-tert-butyryl-1H-indole (3 o) (1- (5-fluoro-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4-fluorophenyl) tert-butyramide (1 o) (39.1 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded 3o (28.9 mg, 66%) as a white solid (The general procedure was followed by using N- (4-fluorophenyl) pivalamide (1 o) (39.1 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3o (28.9 mg, 66%) as a white solid). M.p =62-65 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.46(dd,J＝9.1,4.8Hz,1H),7.77(d,J＝3.8Hz,1H),7.19(dd,J＝8.6,2.6Hz,1H),7.07–7.03(m,1H),6.57(d,J＝3.8Hz,1H),1.51(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝176.9,159.6(d,J＝239.9Hz),133.2,130.4(d,J＝10.1Hz),127.2,118.4(d,J＝9.2Hz),112.8(d,J＝24.4Hz),108.0(d,J＝3.3Hz),106.1(d,J＝24.0Hz),41.3,28.8. 19 F NMR(565MHz)δ＝-119.69–-119.65(m).HR-MS(ESI)m/z calcd for:C 13 H 15 FNO + [M+H + ]220.1132,found 220.1131.
5-chloro-N-tert-butyryl-1H-indole (3 p) (1- (5-chloro-1H-indo-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4-chlorophenyl) tert-butyramide (1 p) (39.4 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Separating and purifying by column chromatography (petroleum ether/ethyl acetate: 80/1- > 40/1)Yellow solid 3p (33.5 mg, 71%) (The general procedure was followed by using N- (4-chlorophenyl) pivalamide (1 p) (39.4 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1.fwdarw.40/1) yielded 3p (.5 mg, 71%) as a yellow solid). M.p =101-104 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.43(d,J＝8.9Hz,1H),7.75(d,J＝3.8Hz,1H),7.51(d,J＝2.2Hz,1H),7.28(dd,J＝8.9,2.2Hz,1H),6.55(d,J＝3.8Hz,1H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.1,135.2,130.7,129.1,127.0,125.3,120.2,118.4,107.6,41.4,28.7.HR-MS(ESI)m/z calcd for:C 13 H 15 ClNO + [M+H + ]236.0837,found 236.0835.
5-bromo-N-tert-butyryl-1H-indole (3 q) (1- (5-bromoo-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4-bromophenyl) tert-butyramide (1 q) (51.2 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/Ethyl acetate: 80/1. Fwdarw.40/1) afforded 3q (39.5 mg, 71%) as a yellow solid (The general procedure was followed by using N- (4-bromobenzyl) pivalamide (1 q) (51.2 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3q (39.5 mg, 71%) as a yellow solid) M.p =116-119 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.38(d,J＝8.9Hz,1H),7.73(d,J＝3.9Hz,1H),7.67(d,J＝2.0Hz,1H),7.42(dd,J＝8.9,2.0Hz,1H),6.54(d,J＝3.9Hz,1H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.1,135.5,131.2,128.0,126.8,123.2,118.8,116.8,107.5,41.4,28.7.HR-MS(ESI)m/z calcd for:C 13 H 15 BrNO + [M+H + ]278.0186,found 278.0187.
5-iodo-N-tert-butyryl-1H-indole (3 r) (1- (5-iodoo-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (4-iodophenyl) tert-butyramide (1 r) (60.6 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/Ethyl acetate: 60/1. Fwdarw.25/1) afforded a red solid 3r (47.2 mg, 72%) (The general procedure was followed by using N- (4-iodophenyl) pivalamide (1 r) (60.6 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum ether/EtOAc: 60/1. Fwdarw.25/1) yielded 3r (47.2 mg, 72%) as a red solid). M.p =103-106 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.26(d,J＝8.8Hz,1H),7.88(d,J＝1.8Hz,1H),7.69(d,J＝3.8Hz,1H),7.60(dd,J＝8.8,1.8Hz,1H),6.53(d,J＝3.8Hz,1H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.1,136.1,133.6,131.8,129.4,126.5,119.2,107.2,87.7,41.4,28.7.HR-MS(ESI)m/z calcd for:C 13 H 15 INO + [M+H + ]328.0193,found 328.0194.
5-trifluoromethyl-N-tert-butyryl-1H-indole (3 s) (2, 2-dimethyl-1- (5- (trifluoromethyl) -1H-indol-1-yl) pro-pan-1-one) starting from N- (4- (trifluoromethyl) phenyl) tert-butyramide (1 s) (49.1 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 70/1. Fwdarw.30/1) afforded 3s (24.3 mg, 45%) of a yellow solid (The general procedure was followed by using N- (4- (trifluoromethyl) phenyl) pivalamide (1 s) (49.1 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 70/1. Fwdarw.30/1) yielded 3s (24.3 mg, 45%) as a yellow solid) M.p =55-58 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.59(d,J＝8.8Hz,1H),7.83(d,J＝3.8Hz,1H),7.80(s,1H),7.58(d,J＝8.8Hz,1H),6.68(d,J＝3.8Hz,1H),1.52(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.3,138.4,129.1,127.3,125.9(q,J＝33.4Hz),124.8(q,J＝272.4Hz),121.9(d,J＝2.9Hz),118.0(d,J＝3.6Hz),117.6,108.3,41.5,28.7. 19 F NMR(565MHz)δ＝-61.06(s).HR-MS(ESI)m/z calcd for:C 14 H 15 F 3 NO + [M+H + ]270.1100,found 270.1096.
5-phenyl-N-tert-butyryl-1H-indole (3 t) (2, 2-dimethyl-1- (5-phenyl-1H-indol-1-yl) pro-pan-1-one) in the form of N- ([ 1,1' -biphenyl)]4-yl) t-butyramide (1 t) (50.7 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared starting materials. Separation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded 3t (47.0 mg, 85%) as a pink solid (The general procedure was followed by using N- ([ 1,1' -biphenyl)]-4-yl)pivalamide(1t)(50.7mg,0.20mmol)and 1,3-dioxol-2-one(2)(68.8mg,0.8mmol).Purification by column chromatography(Petroleum ether/EtOAc:80/1→40/1)yielded 3t(47.0mg,85％)as a pink solid).M.p＝126-129℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.60(d,J＝8.5Hz,1H),7.79(d,J＝1.8Hz,1H),7.77(d,J＝3.8Hz,1H),7.69–7.65(m，2H),7.62(dd,J＝8.5,1.8Hz,1H),7.48–7.45(m,2H),7.36(m,1H),6.68(d,J＝3.8Hz,1H),1.55(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.2,141.6,137.0,136.3,130.1,128.9,127.5,127.0,126.4,124.7,119.0,117.6,108.6,41.4,28.8.HR-MS(ESI)m/z calcd for:C 19 H 20 NO + [M+H + ]278.1539,found 278.1537.
5-ethoxycarbonyl-N-tert-butyryl-1H-indole (3 u) (Ethyl 1-pivaloyl-1H-endole-5-carboxylate) was prepared starting from 4-tert-butyramide benzoate (1 u) (49.9 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). The yellow oily matter 3u (32) is obtained by separation and purification through column chromatography (petroleum ether/ethyl acetate: 70/1- & gt 30/1).3mg,59％)(The general procedure was followed by using ethyl 4-pivalamidobenzoate(1u)(49.9mg,0.20mmol)and 1,3-dioxol-2-one(2)(68.8mg,0.8mmol).Purification by column chromatography(Petroleum ether/EtOAc:70/1→30/1)yielded 3u(32.3mg,59％)as a yellow oil.) 1 H NMR(600MHz,CDCl 3 )δ＝8.52(d,J＝8.7Hz,1H),8.27(s,1H),8.02(d,J＝8.7Hz,1H),7.77(d,J＝3.8Hz,1H),6.66(d,J＝3.8Hz,1H),4.38(q,J＝7.1Hz,2H),1.50(s,9H),1.40(t,J＝7.1Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ＝177.2,167.0,139.5,129.2,126.9,126.4,125.8,122.73,117.0,108.7,61.0,41.4,28.7,14.5.HR-MS(ESI)m/z calcd for:C 16 H 20 NO 3 + [M+H + ]274.1438,found 274.1436.
7-phenyl-N-tert-butyryl-1H-indole (3 v) (2, 2-dimethyl-1- (7-phenyl-1H-indol-1-yl) pro-pan-1-one) in the form of N- ([ 1,1' -biphenyl)]-2-yl) t-butyramide (1 v) (50.7 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) were prepared starting materials. Separation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) gives 3v (36.0 mg, 65%) as an orange solid (The general procedure was followed by using N- ([ 1,1' -biphenyl)]-2-yl)pivalamide(1v)(50.7mg,0.20mmol)and 1,3-dioxol-2-one(2)(68.8mg,0.8mmol).Purification by column chromatography(Petroleum ether/EtOAc:80/1→40/1)yielded 3v(36.0mg,65％)as an orange solid).M.p＝111-114℃. 1 H NMR(600MHz,CDCl 3 )δ＝7.60–7.9(m,1H),6.58(d,J＝3.6Hz,1H),7.46–7.38(m,4H),7.37–7.30(m,2H),7.28–7.26(m,1H),6.56(d,J＝3.6Hz,1H),1.35(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.4,142.0,134.5,131.6,130.7,128.6,127.4,126.8,126.7,126.3,123.6,119.9,107.4,41.5,28.8.HR-MS(ESI)m/z calcd for:C 19 H 20 NO + [M+H + ]278.1539,found 278.1538.
6-methyl-N-t-butyryl-1H-indole (3 w) (2, 2-dimethyl-1- (6-methyl-1H-indol-1-yl) pro-pan-1-one) prepared from N- (3-methylphenyl) t-butyramide (1 w) (38.3 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) as raw materials. Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded yellow solid 3w (35.4 mg, 82%) (The general procedure was followed by using N- (m-tolyl) pivalamide (1 w) (38.3 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3w (35.4 mg, 82%) as a yellow solid) M.p =52-54 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.38(s,1H),7.66(d,J＝3.8Hz,1H),7.43(d,J＝8.1Hz,1H),7.10(d,J＝8.1Hz,1H),6.56(d,J＝3.8Hz,1H),2.48(s,3H),1.51(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.3,137.2,135.3,127.2,125.1,125.0,120.1,117.7,108.3,41.3,28.8,22.1.HR-MS(ESI)m/z calcd for:C 14 H 18 NO + [M+H + ]216.1383,found 216.1383.
6-bromo-N-tert-butyryl-1H-indole (3 x) (1- (6-bromoo-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (3-bromophenyl) tert-butyramide (1 x) (51.2 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded 3x (35.7 mg, 47%) as a yellow solid (The general procedure was followed by using N- (3-bromobenzyl) pivalamide (1 x) (51.2 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol). Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3x (35.7 mg, 47%) as a yellow solid). M.p =86-89 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.74(s,1H),7.70(d,J＝3.8Hz,1H),7.40–7.36(m,2H),6.57(d,J＝3.8Hz,1H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.1,137.5,128.3,126.9,126.2,121.6,120.5,119.0,108.1,41.4,28.7.HR-MS(ESI)m/z calcd for:C 13 H 13 BrNO — [M-H + ]278.0186,found 278.0188.
6-tert-butyl-N-tert-butyryl-1H-indole (3 y) (1- (6- (tert-butyl) -1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared starting from N- (3- (tert-butyl) phenyl) tert-butyramide (1 y) (46.6 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). The white solid 3y (31 mg, 60%) (The general procedure was followed by using N- (3- (tert-butyl) phenyl) pivalamide (1 y) (46.6 mg,0.2 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum/EtOAc: 50/1→30/1) yielded 3y (31 mg, 60%) as a white solid (M.p =95-96 ℃). 1 H NMR(600MHz,CDCl 3 )δ＝8.64(s,1H),7.69(d,J＝3.6Hz,1H),7.48(d,J＝8.2Hz,1H),7.36(dd,J＝8.2,1.8Hz,1H),6.57(d,J＝3.6Hz,1H),1.52(s,9H),1.40(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.4,148.8,137.2,127.2,125.6,121.6,119.9,114.2,108.1,41.4,35.3,31.9,28.8.HR-MS(ESI)m/z calcd for:C 17 H 24 NO + [M+H + ]258.1852,found 258.1854.
Prepared starting from N- (3-methoxyphenyl) t-butyramide (1 z) (41.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 80/1. Fwdarw.40/1) afforded yellow solid 3z and 3z '(2.7:1) (36.1 mg, 78%) (The general procedure was followed by using N- (3-methoxyphenyl) pivalamide (1 z) (41.5 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3zand 3z' (2.7:1) (36).1mg,78％)as a yellow solid).HR-MS(ESI)m/z calcd for:C 14 H 18 NO 2 + [M+H + ]232.1332,found 232.1330.
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4-methoxy-N-tert-butyryl-1H-indole (3 z) (1- (6-methoxy-1H-indol-1-yl) -2, 2-dimethylpropan-1-one): 1 H NMR(600MHz)δ＝8.17(d,J＝2.1Hz,1H),7.63(d,J＝3.8Hz,1H),7.42(d,J＝8.4Hz,1H),6.92(dd,J＝8.4,2.1Hz,1H),6.55(d,J＝3.8Hz,1H),3.89(s,3H),1.52(s,9H). 13 C NMR(150MHz)δ＝177.5,158.5,137.8,126.1,124.5,120.9,113.3,108.3,101.3,55.7,41.4,28.7.HR-MS(ESI)m/z calcd for:C 14 H 18 NO 2 + [M+H + ]232.1332,found 232.1330.
4-methoxy-N-tert-butyryl-1H-indole (3 z') (1- (4-methoxy-1H-indol-1-yl) -2, 2-dimethylpropan-1-one): 1 H NMR(600MHz)δ＝8.12(d,J＝8.3Hz,1H),7.64(d,J＝3.9Hz,1H),7.28(dd,J＝8.3,7.9Hz,1H),6.76(d,J＝3.9Hz,1H),6.72(d,J＝7.9Hz,1H),3.94(s,3H),1.52(s,9H). 13 H NMR(150MHz)δ＝177.3,152.7,138.1,124.2,123.2,119.7,110.5,105.3,104.1,55.5,41.4,28.7.HR-MS(ESI)m/z calcd for:C 14 H 18 NO 2 + [M+H + ]232.1332,found 232.1330.
6-methyl-5-methoxy-N-t-butyryl-1H-indole (3 za)
(1- (5-methoxy-4-methyl-1H-1-yl) -2, 2-dimethylpropan-1-one) prepared from N- (4-methoxy-3-methylphenyl) t-butyramide (1 za) (44.2 mg,0.2 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol)Is prepared. The white solid 3za (31 mg, 64%) (The general procedure was followed by using N- (4-methoxy-3-methylphenyl) pivalamide (1 za) (44.2 mg,0.2 mmol) and 1, 3-dioxal-2-one (2) (68.8, 0.8 mmol). Purification by column chromatography (Petroleum/EtOAc: 20/1. Fwdarw.10/1) yielded 3za (31 mg, 64%) as a white solid was isolated and purified by column chromatography (Petroleum ether/ethyl acetate: 20/1. Fwdarw.10/1). 1 H NMR(600MHz,CDCl 3 )δ＝8.32(s,1H),7.62(d,J＝3.7Hz,1H),6.93(s,1H),6.52(d,J＝3.7Hz,1H),3.86(s,3H),2.33(s,3H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.0,155.0,131.1,128.1,125.1,125.0,119.1,108.2,100.7,55.6,41.2,28.9,17.2.HR-MS(ESI)m/z calcd for:C 15 H 20 NO 2 + [M+H + ]246.1489,found 246.1493.
5, 6-dimethoxy-N-t-butyryl-1H-indole (3 zb)
(1- (5, 6-Dimethoxy-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared from N- (3, 4-dimethoxyphenyl) t-butyramide (1 zb) (47.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) as raw materials. Isolation and purification by column chromatography (Petroleum ether/ethyl acetate: 50/1- > 15/1) afforded a black solid 3zb (31.4 mg, 60%) (The general procedure was followed by using N- (3, 4-dimethoxyphenyl) pivalamide (1 zb) (47.5 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 50/1- > 15/1) yielded 3zb (31.4 mg, 60%) as a black solid). M.p =113-116 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝8.16(s,1H),7.60(d,J＝3.7Hz,1H),6.98(s,1H),6.50(d,J＝3.7Hz,1H),3.95(s,3H),3.91(s,3H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.3,148.2,146.9,131.1,124.3,122.2,108.3,102.0,101.1,56.2,56.2,41.3,28.9.HR-MS(ESI)m/z calcd for:C 15 H 20 NO 3 + [M+H + ]262.1438,found 262.1436.
4, 6-dimethoxy-N-t-butyryl-1H-indole (3 zc)
(1- (4, 6-Dimethoxy-1H-indol-1-yl) -2, 2-dimethylpropan-1-one) prepared from N- (3, 5-dimethoxyphenyl) t-butyramide (1 zc) (47.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol) as raw materials. Isolation and purification by column chromatography (Petroleum/Ethyl acetate: 50/1. Fwdarw.20/1) afforded 3zc (40.3 mg, 77%) as a brown oil (The general procedure was followed by using N- (3, 5-dimethoxyphenyl) pivalamide (1 zc) (47.5 mg,0.20 mmol) and 1, 3-dioxal-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 50/1. Fwdarw.20/1) yielded 3zc (40.3 mg, 77%) as a black oil. 1 H NMR(600MHz,CDCl 3 )δ＝7.73(s,1H),7.52(d,J＝3.8Hz,1H),6.65(d,J＝3.8Hz,1H),6.38(s,1H),3.88(s,3H),3.87(s,3H),1.50(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝177.7,159.7,152.9,138.4,122.8,113.8,105.3,95.4,93.5,55.8,55.5,41.4,28.7.HR-MS(ESI)m/z calcd for:C 15 H 20 NO 3 + [M+H + ]262.1438,found 262.1438.
N-tert-butyryl-1H-benzo [ f ]]Indole (3 zd) (1- (1H-benzol [ f)]Indol-1-yl) -2,2-dimethylpropan-1-one prepared from N- (naphthalen-2-yl) t-butyramide (1 zd) (45.5 mg,0.20 mmol) and vinylene carbonate (2) (68.8 mg,0.8 mmol). Isolation and purification by column chromatography (Petroleum/Ethyl acetate: 80/1. Fwdarw.40/1) afforded 3zd (32.7 mg, 65%) as a yellow solid (The general procedure was followed by using N- (naphthalen-2-yl) pivalamide (1 zd) (45.5 mg,0.20 mmol) and 1,3-dioxol-2-one (2) (68.8 mg,0.8 mmol) Purification by column chromatography (Petroleum ether/EtOAc: 80/1. Fwdarw.40/1) yielded 3zd (32.7 mg, 65%) as a yellow solid) M.p =186-189 ℃. 1 H NMR(600MHz,CDCl 3 )δ＝9.07(s,1H),8.00(s,1H),7.99–7.97(m,1H),7.93-7.90(m,1H),7.88(d,J＝3.9Hz,1H),7.47–7.41(m,2H),6.73(d,J＝3.9Hz,1H),1.55(s,9H). 13 C NMR(150MHz,CDCl 3 )δ＝176.8,136.2,132.2,130.8,129.9,129.0,128.7,127.9,124.9,124.7,118.3,115.1,108.6,41.2,28.7.HR-MS(ESI)m/z calcd for:C 17 H 18 NO + [M+H + ]252.1383,found 252.1383.
While specific embodiments of the invention have been described in detail in connection with the examples, it should not be construed as limiting the scope of protection of the patent. Various modifications and variations which may be made by those skilled in the art without the creative effort are within the scope of the patent described in the claims.

Claims (4)

1. Ruthenium catalysisN-The method for synthesizing indole compounds by aryl amide compounds and vinylene carbonate is characterized by comprising the following steps:
s1: will beN-Mixing an aryl amide substrate, vinylene carbonate, a ruthenium catalyst, a first additive and a second additive, adding an organic solvent under the protection of inert gas, uniformly stirring, and reacting at 75-85 ℃ for 20-30 hours to obtain a primary product; the saidN-The molar ratio of the aryl amide substrate to the vinylene carbonate is 1:3-5; the addition amounts of the ruthenium catalyst, the first additive and the second additive are respectivelyN-4-7%, 18-22% and 8-12% of the total molar weight of the aryl amide substrate and the vinylene carbonate; the first additive is AgSbF 6 The method comprises the steps of carrying out a first treatment on the surface of the The second additive is Zn (OAc) 2 The method comprises the steps of carrying out a first treatment on the surface of the The organic solvent is ethylene glycol dimethyl ether; the ruthenium catalyst is [ RuCl ] 2 (p-cymene)] 2 ；
S2: sequentially extracting and performing column chromatography treatment on the initial product to obtain indole compounds.
2. Ruthenium catalyst according to claim 1N-The method for synthesizing indole compounds by aryl amide compounds and vinylene carbonate is characterized by comprising the following steps of: the reaction temperature in S1 was 80℃and the reaction time was 24h.
3. Ruthenium catalyst according to claim 1N-The method for synthesizing indole compounds by aryl amide compounds and vinylene carbonate is characterized in that the extraction method in S2 is as follows: adding a mixed solution of water and ethyl acetate into the initial product, uniformly stirring, standing until complete layering, and then separating an organic layer and a water layer; repeating the above operation twice, drying and concentrating the organic layer to complete the extraction of the primary product; the volume ratio of the water to the ethyl acetate in the mixed solution of the water and the ethyl acetate is 1-2:1.
4. Ruthenium catalyst according to claim 1N-The method for synthesizing indole compounds from aryl amide compounds and vinylene carbonate is characterized in that a column used for column chromatography in S2 is a silica gel column, and a chromatographic solution is a mixed solution of petroleum ether and ethyl acetate according to a volume ratio of 50:1-10:1.
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