A method for preparing indoleazine compound

Abstract

The present invention provides a method for preparing an indolizine compound, comprising the following steps: adding a compound 1 represented by formula (I) and a compound 2 represented by formula (II) into a solvent, then adding trifluoromethanesulfonic anhydride and a base in an ice-water bath, and then reacting at room temperature to obtain an indolizine compound represented by formula (III); the reaction equation is as follows: #imgabs0# wherein R 1 It is any one of C1-C10 alkyl, benzyl, phenyl, substituted phenyl, condensed ring aromatic group, and heteroaromatic group; X is S or Se. The reaction of the present invention has the advantages of simple operation, no need for transition metal catalyst and air as oxidant, wide substrate applicability, mild reaction conditions, etc., and functionalized indolizine compounds are efficiently constructed.

Description

Technical Field

[0001] The present invention relates to the technical field of compound preparation, and in particular to a method for preparing an indoleazine compound. Background Art

[0002] Indoleazine structure is a special type of nitrogen-containing skeleton, which is commonly found in natural products and drug molecules. For example, the compounds AF shown in the following structural formula, wherein the compounds AD having indoleazine structural units respectively have anti-tuberculosis, anti-acetylcholine, anti-diabetic and anti-inflammatory activities. In addition, compound E has antioxidant activity, and compound F (STA-5312) has cytotoxic activity against certain cancer cell lines.

[0003]

[0004] Due to the remarkable biological activity of indolizine derivatives, chemists have been committed to the synthesis of indolizine derivatives. For example, the synthesis of Chichibabin indolizine; cycloaddition reaction of pyridine or C2-substituted pyridine. In addition, other pyridine analogs can also be converted into indolizine through copper-catalyzed carbene transfer reaction; or formal [3+2] cycloaddition reaction with 1-cyanocyclopropane 1-ester under iodine catalysis; or tandem cyclization reaction with enaminones promoted by phenylboronic acid ester. However, most of these methods for synthesizing indolizine inevitably use transition metals, bases, oxidants or harsh reaction conditions, which limits the efficient and large-scale preparation of indolizine. Therefore, the development of environmentally friendly and efficient methods for preparing indolizine skeletons from simple substrates remains an important topic of current research. Summary of the invention

[0005] To solve the above problems, the present invention aims to provide a method for preparing an indoleazine compound.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows.

[0007] A method for preparing an indolizine compound comprises the following steps:

[0008] Compound 1 represented by formula (I) and compound 2 represented by formula (II) are added to a solvent, and then trifluoromethanesulfonic anhydride and a base are added in an ice-water bath (0-5° C.), followed by reaction at room temperature to obtain an indolizine compound represented by formula (III); the reaction equation is as follows:

[0009]

[0010] In the formula, R 1 It is any one of C1-C10 alkyl, benzyl, phenyl, substituted phenyl, condensed ring aryl, and heteroaryl; X is S or Se.

[0011] Further, R 1 It is any one of isobutyl, benzyl, phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, 2-methylphenyl, 3-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2-naphthyl and 2-thienyl.

[0012] Furthermore, the molar ratio of compound 1 represented by formula (I) to compound 2 represented by formula (II) is 1:1.5.

[0013] Furthermore, the molar ratio of the compound 1 represented by formula (I) to trifluoromethanesulfonic anhydride is 1:1.2-1.5.

[0014] Furthermore, the molar ratio of the compound 1 represented by formula (I) to the base is 1:3-4.

[0015] Furthermore, the solvent is any one of dichloromethane, acetonitrile and toluene.

[0016] Furthermore, the base is any one of DABCO, triethylamine, diisopropylethylamine and diisopropylamine.

[0017] Furthermore, the reaction time at room temperature is 8 to 24 hours.

[0018] Beneficial effects of the present invention:

[0019] 1. The reaction of the present invention is simple to operate, does not require transition metal catalysts and air as an oxidant, has the advantages of wide substrate applicability, mild reaction conditions, and efficiently constructs functionalized indolizine compounds.

[0020] 2. The present invention uses arylthiophenol as a template substrate and trifluoromethanesulfonic anhydride (Tf2O) as an activation reagent, and can generate indolizine compounds with a high yield (70%-94%) under the action of DABCO base. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Example 16 of the present invention is different substrate R 1 XH conducted a confirmatory exploration of the optimal conditions for the reaction process and the structural formulas of each product. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0023] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making any creative work shall fall within the scope of protection of the present invention.

[0024] Tf2O trifluoromethanesulfonic anhydride; p-tolyl p-tolyl.

[0025] Unless otherwise specified, the experimental methods described in the following examples are all conventional methods; the reagents and materials described are all commercially available unless otherwise specified.

[0026] Example 1

[0027] A method for preparing an indolizine compound comprises the following steps:

[0028] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of triethylamine were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0029] Example 2

[0030] A method for preparing an indolizine compound comprises the following steps:

[0031] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of diisopropylethylamine were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0032] Example 3

[0033] A method for preparing an indolizine compound comprises the following steps:

[0034] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of diisopropylamine were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0035] Example 4

[0036] A method for preparing an indolizine compound comprises the following steps:

[0037] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DBU were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0038] Example 5

[0039] A method for preparing an indolizine compound comprises the following steps:

[0040] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0041] Example 6

[0042] A method for preparing an indolizine compound comprises the following steps:

[0043] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of K2CO3 were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0044] Example 7

[0045] A method for preparing an indolizine compound comprises the following steps:

[0046] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of dichloromethane, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of 2-fluoro-pyridine were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0047] Example 8

[0048] A method for preparing an indolizine compound comprises the following steps:

[0049] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0050] Example 9

[0051] A method for preparing an indolizine compound comprises the following steps:

[0052] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of toluene, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0053] Example 10

[0054] A method for preparing an indolizine compound comprises the following steps:

[0055] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.4 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0056] Embodiment 11

[0057] A method for preparing an indolizine compound comprises the following steps:

[0058] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.24 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 12 h to obtain an indolizine compound (3ab).

[0059] Example 12

[0060] A method for preparing an indolizine compound comprises the following steps:

[0061] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) was added in an ice-water bath (0°C), followed by reaction at room temperature for 12 hours to obtain an indolizine compound (3ab).

[0062] Embodiment 13

[0063] A method for preparing an indolizine compound comprises the following steps:

[0064] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 24 hours to obtain an indolizine compound (3ab).

[0065] Embodiment 14

[0066] A method for preparing an indolizine compound comprises the following steps:

[0067] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.8 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 8 h to obtain an indolizine compound (3ab).

[0068] Embodiment 15

[0069] A method for preparing an indolizine compound comprises the following steps:

[0070] 0.2 mmol of (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) and 0.3 mmol of p-methylthiophenol (2b) were added to 2 mL of acetonitrile, and then 0.3 mmol of trifluoromethanesulfonic anhydride (Tf2O) and 0.6 mmol of DABCO were added in an ice-water bath (0°C), followed by reaction at room temperature for 8 h to obtain an indolizine compound (3ab).

[0071] The above embodiments of the present invention mainly use (E)-1-pyridyl-3-dimethylamino-2-propene-1-one 1a and p-methylthiophenol 2b as template substrates and trifluoromethanesulfonic anhydride Tf2O as an activating reagent to optimize the reaction conditions. The optimization of the above reaction conditions of Examples 1 to 15 is shown in Table 1. The chemical reaction equations of Examples 1 to 15 are shown below:

[0072]

[0073] Table 1 Reaction conditions a Optimization

[0074]

[0075]

[0076] Note: a Reaction conditions: 1a (0.2 mmol), 2b (0.3 mmol), Tf2O (0.3 mmol), solvent (2 mL), base (0.8 mmol). b Nitromethane was used as internal standard. 1 The yield was determined by HNMR. c DABCO (0.4 mmol). d Tf2O (0.24 mmol). “-” indicates not added or not calculated.

[0077] As can be seen from the results in Table 1, when dichloromethane is used as solvent and triethylamine is used as base, the yield of the target product indolizine 3ab is 53% (No. 1). By screening the base including diisopropylethylamine, diisopropylamine, 1,8-diazabicycloundec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), potassium carbonate (K2CO3) and 2-fluoropyridine (No. 2-7), we found that the reaction yield was the best when DABCO was used as the base (No. 5, yield 97%). By screening the solvent including acetonitrile and toluene (No. 8-9), we found that when acetonitrile was used as the solvent, the target product indolizine 3ab could be obtained nearly quantitatively (No. 8, 99%). When we reduce the amount of base DABCO or activation reagent Tf2O, the yield of the reaction will also decrease (No. 10-11). When there is no base, the reaction cannot proceed smoothly (No. 12). Finally, we determined the optimal reaction conditions: 1a (1 eq.), 2b (1.5 eq.), acetonitrile as solvent, adding trifluoromethanesulfonic anhydride (1.5 eq.) and DABOC (4 eq.) at 0°C, and reacting at room temperature for 12 hours (No. 8).

[0078] Example 16

[0079] A method for preparing an indolizine compound is substantially the same as the method of Example 8, except that a different substrate R is used. 1 XH, different indolizine compounds were obtained to explore the substrate applicability and to verify the above optimal conditions. See Table 2 and Figure 1 .

[0080] Table 2 Investigation of substrate suitability

[0081] serial number <![CDATA[Substrate R 1 XH]]> Product No. Yield / % 1 Thiophenol 3aa 93 2 4-Methylthiophenol 3ab 92 3 4-tert-Butylthiophenol 3ac 90 4 4-Methoxythiophenol 3ad 93 5 4-Fluorothiophenol 3ae 86 6 4-Chlorothiophenol 3af 88 7 4-Bromothiophenol 3ag 87 8 4-Nitrothiophenol 3ah 94 9 2-Methylthiophenol 3ai 87 10 3-Methylthiophenol 3aj 81 11 2,6-Dimethylthiophenol 3ak 86 12 3,5-Dimethylthiophenol 3al 87 13 2-Naphthylthiol 3am 84 14 2-Thiophenethiol 3an 70 15 Benzyl mercaptan 3ao 56 16 Isobutylmercaptan 3ap 44 17 Phenylselenol 3aq 84

[0082] As can be seen from the results in Table 2, (E)-1-pyridyl-3-dimethylamino-2-propene-1-one (1a) can react with aromatic thiophenols (2) (including thiophenol, 4-methylthiophenol, 4-tert-butylthiophenol, 4-methoxythiophenol, 4-fluorothiophenol, 4-chlorothiophenol, 4-bromothiophenol, 4-nitrothiophenol, 2-methylthiophenol, 3-methylthiophenol, 2,6-dimethylthiophenol, 3,5-dimethylthiophenol, 2-naphthol and 2-thiophenethiol) under the standard conditions of Example 8 to produce indolizine compounds (3) (3aa-3an, yields of 70%-94%) in high yields.

[0083] (E)-1-Pyridyl-3-dimethylamino-2-propene-1-one (1a) can also react with alkyl mercaptans (including benzyl mercaptan, isobutyl mercaptan) or phenylselenol under the standard conditions of Example 8 to obtain the corresponding products 3ao-3aq in yields of 44-84%.

[0084] The above results show that the reaction method of the embodiment of the present invention is simple to operate, does not require a transition metal catalyst and air as an oxidant, has a wide substrate applicability, and has mild reaction conditions. It can efficiently construct functionalized indolizine compounds with a high separation yield.

[0085] Below we list the NMR data of some compounds.

[0086] N,N-dimethyl-1-(phenylthio)indolizin-3-amine(3aa)

[0087]

[0088] Yellow liquid (49.9 mg, 93%, R f =0.55, PE:EA=20:1): 1 HNMR(400MHz, CDCl3)δ7.94(d,J=7.1Hz,1H),7.51(d,J=9.0Hz,1H),7.18–7.12(m,2H),7.05–7 .00(m,3H),6.73(dd,J=8.5,6.8Hz,1H),6.60(dd,J=9.9,3.5Hz,1H),6.52(s,1H),2.77(s,6H). 13CNMR(100MHz, CDCl3)δ141.0,136.7,132.3,128.6,125.3,124.4,121.8,118.0,117.6,110.8,107.4,94.2,44.0; HRMS(ESI)m / z[M] + :Calcdfor[C 16 H 16 N2S] + :268.1034.Found:268.1036.

[0089] N,N-dimethyl-1-(p-tolylthio)indolizin-3-amine(3ab)

[0090]

[0091] Yellow solid (51.9 mg, 92%, Rf = 0.55, PE:EA = 20:1, mp = 60-61 ° C): 1 H NMR(400MHz, CDCl3)δ7.92(d,J=7.1Hz,1H),7.52(dt,J=9.0,1.1Hz,1H),7.09–6.89(m,4H), 6.72(ddd,J=9.0,6.5,1.0Hz,1H),6.63–6.56(m,1H),6.51(s,1H),2.76(s,6H),2.24(s,3H). 13 C NMR (100MHz, CDCl3) δ137.3,136.6,134.3,132.2,129.4,125.7,121.7,117.8,117.7,110.7,107.4,95.0,44.0,20.9; HRMS (ESI) m / z[M] + :Calcd for[C 17 H 18 N2S] + :282.1191.Found:282.1192.

[0092] 1-((4-fluorophenyl)thio)-N,N-dimethylindolizin-3-amine(1-((4-fluorophenyl)thio)-N,N-dimethylindolizin-3-amine, 3ae)

[0093]

[0094] Yellow liquid (49.2mg, 86%, R f =0.50, PE:EA=20:1): 1 H NMR(400MHz, CDCl3)δ7.94(d,J=7.0Hz,1H),7.51(d,J=9.0Hz,1H),7.03–6.96(m,2H),6.91 –6.82(m,2H),6.74(dd,J=8.9,6.5Hz,1H),6.61(t,J=6.7Hz,1H),6.50(s,1H),2.76(s,6H). 13 C NMR(100MHz,CDCl3)δ160.7(d,J C-F =243.3Hz),136.7,135.9(d,J C-F =3.0Hz),132.2,127.2(d,J C-F =7.7Hz),121.8,118.1,117.5,115.6(d,J C-F =22.0Hz),110.8,107.3,94.8,44.0; 19 FNMR(376MHz, CDCl3)δ-118.87; HRMS(ESI)m / z[M] + :Calcd for[C 16 H 15 N2FS + :286.0940.Found:286.0942.

[0095] N,N-dimethyl-1-(thiophen-2-ylthio)indolizin-3-amine

[0096]

[0097] Yellow liquid (38.4mg, 70%, R f =0.51, PE:EA=20:1): 1 HNMR (400MHz, CDCl3) δ7.87(d,J=7.0Hz,1H),7.66(d,J=9.0Hz,1H),7.12(dd,J=5.3,1.2Hz,1H),7.00(dd,J=3.5, 1.2Hz, 1H), 6.85 (dd, J=5.3, 3.6Hz, 1H), 6.76 (dd, J=8.5, 6.9Hz, 1H), 6.60–6.54 (m, 1H), 6.53 (s, 1H), 2.72 (s, 6H).13 CNMR(100MHz, CDCl3)δ140.2,136.2,131.2,128.5,127.2,126.6,121.7,117.9,117.6,110.7,106.5,98.3,44.0; HRMS(ESI)m / z[M] + :Calcdfor[C 14 H 14 N2S2] + :274.0598.Found:274.0596.

[0098] 1-(benzylthio)-N,N-dimethylindolizin-3-amine(1-(benzylthio)-N,N-dimethylindolizin-3-amine, 3ao)

[0099]

[0100] Yellow liquid (31.6 mg, 56%, R f =0.54, PE:EA=20:1): 1 HNMR (400MHz, CDCl3) δ7.84(d,J=7.0Hz,1H),7.33(d,J=9.0Hz,1H),7.18(dd,J=5.0,1.8Hz,3H),7.06(dd,J= 6.7, 2.8Hz, 2H), 6.61 (ddd, J=8.9, 6.4, 1.0Hz, 1H), 6.55–6.48 (m, 1H), 6.22 (s, 1H), 3.79 (s, 2H), 2.69 (s, 6H). 13 CNMR(100MHz, CDCl3)δ139.2,135.8,131.6,129.0,128.1,126.6,121.4,117.7,116.9,110.3,107.3,97.7,44.0,42.8; HRMS(ESI)m / z[M] + :Calcdfor[C 17 H 18 N2S] + :282.1191.Found:282.1192.

[0101] N,N-dimethyl-1-(phenylselanyl)indolizin-3-amine

[0102]

[0103] Yellow liquid (53.1 mg, 84%, R f =0.51, PE:EA=20:1): 1 HNMR(400MHz, CDCl3) δ7.93(d,J=7.1Hz,1H),7.51(d,J=9.0Hz,1H),7.19–7. 04(m,5H),6.72(ddd,J=9.0,6.4,0.9Hz,1H),6.62–6.53(m,2H),2.77(s,6H). 13 CNMR(100MHz, CDCl3)δ136.9,135.4,132.4,128.9,128.2,125.3,121.7,118.6,117.7,110.6,108.5,90.2,44.0; HRMS(ESI)m / z[M] + :Calcdfor[C 16 H 16 N2Se] + :316.0479.Found:316.0479.

[0104] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an indolizine compound, characterized in that: The following steps are involved: Compound 1 represented by formula (I) and compound 2 represented by formula (II) are added to a solvent, and then trifluoromethanesulfonic anhydride and a base are added under an ice-water bath, and then reacted at room temperature to obtain an indolizine compound represented by formula (III); the reaction equation is as follows: In the formula, R 1 It is any one of C1-C10 alkyl, benzyl, phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, 2-methylphenyl, 3-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, condensed ring aromatic group and heteroaromatic group; X is S or Se; and the base is any one of DABCO, triethylamine, diisopropylethylamine and diisopropylamine.

2. The method for preparing the indoleazine compound according to claim 1, characterized in that: The molar ratio of compound 1 represented by formula (I) to compound 2 represented by formula (II) is 1:1.

5.

3. The method for preparing the indolizine compound according to claim 1, characterized in that: The molar ratio of the compound 1 represented by formula (I) to trifluoromethanesulfonic anhydride is 1:1.2-1.

5.

4. The method for preparing the indolizine compound according to claim 1, characterized in that: The molar ratio of the compound 1 represented by formula (I) to the base is 1:3-4.

5. The method for preparing the indolizine compound according to claim 1, characterized in that: The solvent is any one of dichloromethane, acetonitrile and toluene.

6. The method for preparing the indolizine compound according to claim 1, characterized in that: The reaction time at room temperature is 8 to 24 hours.

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