CN117126119A - Preparation method of (benzo) thiazole amide-containing compound - Google Patents

Preparation method of (benzo) thiazole amide-containing compound Download PDF

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CN117126119A
CN117126119A CN202311086798.1A CN202311086798A CN117126119A CN 117126119 A CN117126119 A CN 117126119A CN 202311086798 A CN202311086798 A CN 202311086798A CN 117126119 A CN117126119 A CN 117126119A
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chloride
amino
compound
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ethyl acetate
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解增洋
唐敬杰
谢露影
杨琦堃
石尚玉
刘嘉昱
孙欣雨
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JINING MEDICAL UNIVERSITY
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D277/82—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/58—Nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention provides a preparation method of a (benzo) thiazole-containing amide compound, and belongs to the technical field of amide compound preparation. The invention mixes the substituted acyl chloride, the compound 1 or the compound 2, the samarium powder and the alkali in a solvent, and reacts under the ultrasonic condition to obtain the (benzo) thiazole amide compound. The samarium powder and alkali are added in the preparation of the (benzo) thiazole amide compound, and the target product is successfully synthesized by an ultrasonic-assisted method, so that the preparation method has the advantages of simplicity in operation, low cost, high product yield, wide substrate application range and the like.

Description

Preparation method of (benzo) thiazole amide-containing compound
Technical Field
The invention relates to the technical field of amide compound preparation, in particular to a preparation method of a (benzo) thiazole-containing amide compound.
Background
Amide compounds are widely used in a variety of products with practical applications, ranging from drugs, peptides (proteins) to synthetic polymers etc. [ see: hummphrey, j.m.; chamberlin, A.R. chem. Rev.1997,97,2243-2266.]. In the field of organic synthesis, amide bonds generally play a critical role in the preparation of other compounds such as nitriles, amines, heterocycles and amino acids.
An important class of amide compounds are compounds containing (benzo) thiazole building blocks in the molecule, which often exhibit different pharmacological and physiological activities, for example: the following compound I (SAR 125844) is a highly selective MET kinase inhibitor; benzothiazole-2, 6-diamine derivative II is an antibacterial agent; compound III showed good tumor growth inhibition against multiple tumors with different genetic backgrounds (U-87 MG, a549 and HCT116 cell lines); the picomolar inhibitors of Src and Bcr-Abl kinase dasatinib (compound IV) have been used clinically; amide V containing thiazole structural units of the formula is useful for treating hepatitis C virus infection; while another thiazole ring-containing amide VI is reported to have excellent moderate metabolic stability and plasma stability.
The prior art for preparing the (benzo) thiazole amide compound has complex process and low yield. Therefore, it is important to develop a process for producing (benzo) thiazole amide-containing compounds, which can improve the yield of the (benzo) thiazole amide-containing compounds.
Disclosure of Invention
The invention aims to provide a preparation method of a (benzo) thiazole-containing amide compound, which aims to solve the problem of low yield of the (benzo) thiazole-containing amide compound in the prior art.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of a (benzo) thiazole amide compound, which comprises the following steps: mixing substituted acyl chloride, a compound 1 or a compound 2, samarium powder and alkali in a solvent, and reacting under ultrasonic to obtain a (benzo) thiazole amide compound;
the structural formula of the substituted acyl chloride isWherein R is 1 Is benzyl, alkyl, aryl or heteroaryl;
the structural formula of the compound 1 isWherein R is 2 And R is 3 Independently chlorine, bromine, nitro, methoxy, methyl or hydrogen; the structural formula of the compound 2 is +.>Wherein R is 4 And R is 5 Independently methyl, bromo or nitro.
Preferably, the substituted acyl chloride is phenylacetyl chloride, 2, 5-dimethylbenzylacetyl chloride, 4-chlorobenzylacetyl chloride, 4-methoxyphenylacetyl chloride, thiopheneacetyl chloride, benzoyl chloride, 2-naphthoyl chloride, 4-tert-butylbenzoyl chloride, furoyl chloride, 2-thiophenecarboxyl chloride or propionyl chloride.
Preferably, the compound 1 is 2-aminothiazole, 2-amino-5-methylthiazole, 2-amino-4-methylthiazole, 2-amino-5-nitrothiazole or 2-amino-5-bromothiazole.
Preferably, the compound 2 is 2-amino-6-chlorobenzothiazole, 2-aminobenzothiazole, 2-amino-6-fluorobenzothiazole, 2-amino-6-bromobenzothiazole, 2-amino-6-nitrobenzothiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole or 2-amino-4-methylbenzothiazole.
Preferably, the base comprises one or more of triethylamine, pyridine, potassium hydroxide, sodium carbonate and potassium carbonate.
Preferably, the solvent comprises one or more of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, ethyl acetate, dichloromethane, N-dimethylformamide and dimethyl sulfoxide.
Preferably, the molar volume ratio of the substituted acyl chloride, the compound 1 or the compound 2, the samarium powder, the alkali and the solvent is 0.4-0.8 mmol:0.4 to 0.8mmol:0.04 to 0.48mmol:0.4 to 0.8mmol: 1-8 mL.
Preferably, the frequency of the ultrasonic wave is 40-50 kHz.
Preferably, the reaction temperature is 0 to 40 ℃ and the reaction time is 15 to 600s.
The invention has the beneficial effects that:
(1) The invention adds samarium powder and alkali when preparing (benzo) thiazole amide compound, and then successfully synthesizes the target product by an ultrasonic auxiliary method.
(2) The invention has the advantages of simple operation, low cost, high product yield, wide substrate application range and the like.
Detailed Description
The invention provides a preparation method of a (benzo) thiazole amide compound, which comprises the following steps: mixing substituted acyl chloride, a compound 1 or a compound 2, samarium powder and alkali in a solvent, and reacting under ultrasonic to obtain a (benzo) thiazole amide compound;
the structural formula of the substituted acyl chloride isWherein R is 1 Is benzyl, alkyl, aryl or heteroaryl;
the structural formula of the compound 1 isWherein R is 2 And R is 3 Independently chlorine, bromine, nitro, methoxy, methyl or hydrogen; the structural formula of the compound 2 is +.>Wherein R is 4 And R is 5 Independently methyl, bromo or nitro.
In the present invention, the substituted acyl chloride is phenylacetyl chloride, 2, 5-dimethylbenzene acetyl chloride, 4-chlorobenzoyl chloride, 4-methoxyphenylacetyl chloride, thiopheneacetyl chloride, benzoyl chloride, 2-naphthoyl chloride, 4-t-butylbenzoyl chloride, furoyl chloride, 2-thiophenoyl chloride or propionyl chloride, preferably phenylacetyl chloride, 2, 5-dimethylbenzene acetyl chloride, 4-chlorobenzoyl acetyl chloride, 4-methoxyphenylacetyl chloride, thiopheneacetyl chloride, furoyl chloride or propionyl chloride, further preferably phenylacetyl chloride, 4-chlorobenzoyl chloride, 4-methoxyphenylacetyl chloride, thiopheneacetyl chloride or propionyl chloride.
In the present invention, the compound 1 is 2-aminothiazole, 2-amino-5-methylthiazole, 2-amino-4-methylthiazole, 2-amino-5-nitrothiazole or 2-amino-5-bromothiazole, preferably 2-aminothiazole, 2-amino-5-methylthiazole or 2-amino-4-methylthiazole, more preferably 2-aminothiazole or 2-amino-5-methylthiazole.
In the present invention, the compound 2 is 2-amino-6-chlorobenzothiazole, 2-aminobenzothiazole, 2-amino-6-fluorobenzothiazole, 2-amino-6-bromobenzothiazole, 2-amino-6-nitrobenzothiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole or 2-amino-4-methylbenzothiazole, preferably 2-amino-6-chlorobenzothiazole, 2-aminobenzothiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole or 2-amino-4-methylbenzothiazole, more preferably 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole or 2-amino-4-methylbenzothiazole.
In the present invention, the base contains one or more of triethylamine, pyridine, potassium hydroxide, sodium carbonate and potassium carbonate, preferably one or more of pyridine, potassium hydroxide and sodium carbonate, and more preferably pyridine and/or potassium hydroxide.
In the present invention, the solvent contains one or more of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, ethyl acetate, dichloromethane, N-dimethylformamide and dimethylsulfoxide, preferably one or more of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, ethyl acetate and dichloromethane, more preferably one or more of tetrahydrofuran, ethanol, acetonitrile and 1, 4-dioxane.
In the invention, the molar volume ratio of the substituted acyl chloride, the compound 1 or the compound 2, the samarium powder, the alkali and the solvent is 0.4-0.8 mmol:0.4 to 0.8mmol: :0.04 to 0.48mmol:0.4 to 0.8mmol:1 to 8mL, preferably 0.5 to 0.7mmol:0.5 to 0.7mmol:0.10 to 0.45mmol:0.5 to 0.7mmol:2 to 7mL, more preferably 0.55 to 0.65mmol:0.55 to 0.65mmol:0.15 to 0.40mmol:0.55 to 0.65mmol: 3-6 mL.
In the present invention, the ultrasonic frequency is 40 to 50kHz, preferably 42 to 48kHz, and more preferably 45kHz.
In the present invention, the temperature of the reaction is 0 to 40 ℃, preferably 5 to 35 ℃, and more preferably 10 to 20 ℃; the time is 15 to 600 seconds, preferably 30 to 550 seconds, and more preferably 50 to 500 seconds.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Mixing 0.5mmol of phenylacetyl chloride, 0.5mmol of 2-amino-6-chlorobenzothiazole, 0.25mmol of samarium powder and 0.5mmol of pyridine in 4mL of tetrahydrofuran, reacting for 60s at 0 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and purifying by flash column chromatography with petroleum ether as a mobile phase to obtain a pure product 3a, wherein the structural formula isThe yield was 94%.
1 H NMR(400MHz,d 6 -DMSO)δ3.85(s,2H),7.27–7.30(m,1H),7.35(d,J＝4.4Hz,4H),7.46(dd,J＝8.6,2.2Hz,1H),7.75(d,J＝8.7Hz,1H),8.12(d,J＝2.1Hz,1H),12.70(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.3,121.9,122.2,126.9,127.4,128.1,128.9,129.8,133.6,135.0,147.8,159.2,170.9.
Example 2
0.4mmol of phenylacetyl chloride, 0.4mmol of 2-aminobenzothiazole, 0.2mmol of samarium powder and 0.4mmol of pyridine are mixed in 5mL of dichloromethane, reacted for 100s at 25 ℃ under the ultrasonic wave with the frequency of 40kHz, and then cisFiltering with diatomite, washing with ethyl acetate, distilling under reduced pressure to remove solvent, and purifying with flash column chromatography with ethyl acetate and petroleum ether as mobile phase to obtain pure product 3b with structural formula ofThe yield was 95%.
1 H NMR(400MHz,d 6 -DMSO)δ3.86(s,2H),7.25–7.31(m,2H),7.32–7.38(m,4H),7.41–7.46(m,1H),7.75(d,J＝7.9Hz,1H),7.96(d,J＝7.9Hz,1H),12.63(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.3,120.9,122.2,124.0,126.6,127.4,128.9,129.8,131.9,135.2,148.9,158.4,170.2.
Example 3
Mixing 0.6mmol of phenylacetyl chloride, 0.6mmol of 2-amino-6-fluorobenzothiazole, 0.3mmol of samarium powder and 0.6mmol of triethylamine in 8mL of ethanol, reacting for 200s at 40 ℃ under the ultrasonic wave with the frequency of 50kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, purifying by flash column chromatography by taking ethyl acetate and petroleum ether as mobile phases to obtain a pure product, namely 3c, with the structural formula ofThe yield was 88%.
1 H NMR(400MHz,d 6 -DMSO)δ3.84(s,2H),7.27–7.32(m,3H),7.35(d,J＝4.5Hz,3H),7.76(dd,J＝8.9,4.8Hz,1H),7.89(dd,J＝8.7,2.6Hz,1H),12.64(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.3,108.6(d,J CF ＝26.9Hz),114.7(d,J CF ＝24.4Hz),122.1(d,J CF ＝9.1Hz),127.0,127.4,128.9,129.8,133.2(d,J CF ＝11.1Hz),135.1,145.7,159.1(d,J CF ＝239.9Hz),170.8.
Example 4
Mixing 0.8mmol of phenylacetyl chloride, 0.8mmol of 2-amino-6-bromobenzothiazole, 0.48mmol of samarium powder and 0.8mmol of sodium carbonate in 7mL of ethyl acetate, reacting for 400s at 0 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, and steaming under reduced pressureDistilling to remove solvent, ethyl acetate and petroleum ether as mobile phase, and performing rapid column chromatography purification to obtain pure product 3d with structural formula ofThe yield was 92%.
1 H NMR(400MHz,d 6 -DMSO)δ3.85(s,2H),7.26–7.30(m,1H),7.35(d,J＝4.5Hz,4H),7.58(dd,J＝8.6,2.1Hz,1H),7.69(d,J＝8.6Hz,1H),8.25(d,J＝1.9Hz,1H),12.71(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.3,115.9,122.6,124.8,127.4,128.9,129.6,129.8,134.1,135.0,148.2,159.2,170.9.HRMS(ESI)m/z:calcd for C 15 H 11 BrN 2 OS(M+H) + 346.9848,found 346.9845.
Example 5
Mixing 0.8mmol of phenylacetyl chloride, 0.8mmol of 2-amino-6-nitrobenzothiazole, 0.15mmol of samarium powder and 0.8mmol of potassium carbonate into 6mL of dimethyl sulfoxide, reacting for 100s at 25 ℃ under 50kHz ultrasonic, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, purifying by flash column chromatography by taking petroleum ether as a mobile phase to obtain a pure product, namely 3e, with the structural formula ofThe yield thereof was found to be 82%.
1 H NMR(400MHz,d 6 -DMSO)δ3.90(s,2H),7.27–7.38(m,5H),7.91(d,J＝9.0Hz,1H),8.29(dd,J＝8.9,2.4Hz,1H),9.06(d,J＝2.4Hz,1H),13.03(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.3,119.5,121.1,122.2,127.5,128.9,129.9,132.7,134.8,143.5,153.9,163.9,171.4.
Example 6
Mixing 0.5mmol of phenylacetyl chloride, 0.5mmol of 2-amino-6-methoxybenzothiazole, 0.30mmol of samarium powder and 0.5mmol of pyridine in 3mL of N, N-dimethylformamide, reacting for 80s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing the solvent by reduced pressure distillation, ethyl acetate and petroleum ether as the componentsPurifying the mobile phase by rapid column chromatography to obtain pure product 3f with structural formula ofThe yield thereof was found to be 97%.
1 H NMR(400MHz,d 6 -DMSO)δ3.56(s,3H),3.81(s,2H),7.02(dd,J＝8.8,2.5Hz,1H),7.24–7.35(m,5H),7.55(d,J＝2.4Hz,1H),7.64(d,J＝8.8Hz,1H),12.45(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42173.2.3,56.1,105.2,115.4,121.6,127.3,128.7,129.8,133.2,135.5,143.1,156.2,170.4.
Example 7
Mixing 0.7mmol of phenylacetyl chloride, 0.7mmol of 2-amino-6-methylbenzothiazole, 0.25mmol of samarium powder and 0.7mmol of potassium hydroxide in 5mL of 1, 4-dioxane, reacting for 360s at 0 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, distilling under reduced pressure to remove solvent, ethyl acetate and petroleum ether as mobile phase, and performing rapid column chromatography purification to obtain a pure product, 3g, with the structural formula ofThe yield was 94%.
1 H NMR(400MHz,d 6 -DMSO)δ2.41(s,3H),3.82(s,2H),7.24–7.36(m,6H),7.63(d,J＝8.2Hz,1H),7.75(s,1H),12.53(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ21.4,42.3,120.6,121.8,127.3,127.9,128.9,129.8,132.0,133.5,135.2,146.9,157.5,170.5.HRMS(ESI)m/z:calcd for C 16 H 14 N 2 OS(M+H) + 283.0900,found 283.0906.
Example 8
Mixing 0.7mmol of phenylacetyl chloride, 0.7mmol of 2-amino-4-methylbenzothiazole, 0.45mmol of samarium powder and 0.7mmol of triethylamine in 8mL of tetrahydrofuran, reacting for 500s at 25 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing the solvent by reduced pressure distillation, purifying by flash column chromatography by taking ethyl acetate and petroleum ether as mobile phases to obtain a pure product, wherein the pure product is 3h in structureIs of the typeThe yield was 90%.
1 H NMR(400MHz,d 6 -DMSO)δ2.58(s,3H),3.83(s,2H),7.20(t,J＝7.6Hz,1H),7.25–7.30(m,2H),7.35–7.38(m,4H),7.78(d,J＝7.8Hz,1H),12.69(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ18.4,42.3,119.6,123.9,127.1,127.4,128.9,129.8,130.3,131.6,135.2,148.1,157.5,170.6.HRMS(ESI)m/z:calcd for C 16 H 14 N 2 OS(M+H) + 283.0900,found 283.0896.
Example 9
Mixing 0.5mmol of phenylacetyl chloride, 0.5mmol of 2-aminothiazole, 0.15mmol of samarium powder and 0.5mmol of triethylamine in 6mL of ethanol, reacting for 600s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and performing rapid column chromatography purification by taking ethyl acetate and petroleum ether as mobile phases to obtain a pure product 3i with the structural formula ofThe yield was 95%.
1 H NMR(400MHz,d 6 -DMSO)δ3.77(s,2H),7.20(d,J＝3.6Hz,1H),7.25–7.34(m,5H),7.47(d,J＝3.6Hz,1H),12.35(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ42.1,113.9,127.3,128.9,129.7,135.5,138.1,158.4,169.6.
Example 10
Mixing 0.6mmol of phenylacetyl chloride, 0.6mmol of 2-amino-5-methylthiazole, 0.15mmol of samarium powder and 0.6mmol of pyridine in 8mL of tetrahydrofuran, reacting for 300s at 25 ℃ under the ultrasonic with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and purifying by flash column chromatography with petroleum ether as a mobile phase to obtain a pure product 3j with the structural formula ofThe yield was 96%.
1 H NMR(400MHz,d 6 -DMSO)δ2.32(s,3H),3.73(s,2H),7.13(s,1H),7.24–7.35(m,5H),12.14(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ11.5,42.1,126.6,127.2,128.9,129.7,135.2,135.6,156.6,169.3.
Example 11
Mixing 0.6mmol of phenylacetyl chloride, 0.6mmol of 2-amino-4-methylthiazole, 0.25mmol of samarium powder and 0.6mmol of triethylamine in 5mL of ethanol, reacting for 500s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and purifying by flash column chromatography with petroleum ether as a mobile phase to obtain a pure product 3k with the structural formula ofThe yield was 92%.
1 H NMR(400MHz,d 6 -DMSO)δ2.26(s,3H),3.73(s,2H),6.74(s,1H),7.24–7.33(m,5H),12.27(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ17.3,42.2,108.1,127.3,128.9,129.7,135.5,147.1,157.7,169.5.
Example 12
Mixing 0.5mmol of phenylacetyl chloride, 0.5mmol of 2-amino-5-nitrothiazole, 0.15mmol of samarium powder and 0.5mmol of potassium carbonate in 7mL of acetonitrile, reacting for 200s at 0 ℃ under the ultrasonic wave with the frequency of 40kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and purifying by flash column chromatography with petroleum ether as a mobile phase to obtain a pure product 3l, wherein the structural formula isThe yield was 69%.
1 H NMR(400MHz,d 6 -DMSO)δ3.88(s,2H),7.22–7.35(m,5H),8.63(s,1H),12.29(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ41.9,127.5,128.7,129.8,134.5,135.5,143.1,162.2,171.6.
Example 13
0.8mmol of phenylacetyl chloride,Mixing 0.8mmol of 2-amino-5-bromothiazole, 0.45mmol of samarium powder and 0.8mmol of potassium hydroxide in 7mL of ethyl acetate, reacting for 450s at 25 ℃ under the ultrasonic with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing the solvent by reduced pressure distillation, purifying by flash column chromatography with ethyl acetate and petroleum ether as mobile phases to obtain a pure product 3m, wherein the structural formula isThe yield was 91%.
1 H NMR(400MHz,d 6 -DMSO)δ3.78(s,2H),7.25–7.35(m,5H),7.56(s,1H),12.62(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ41.8,102.1,127.4,128.9,129.7,135.1,139.2,158.8,170.2.
Example 14
Mixing 0.4mmol of 2, 5-dimethylbenzene acetyl chloride, 0.4mmol of 2-aminothiazole, 0.35mmol of samarium powder and 0.4mmol of potassium hydroxide in 3mL of ethanol, reacting for 500s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, removing ethyl acetate and petroleum ether as mobile phases in sequence, and performing rapid column chromatography purification to obtain a pure product, namely a product 4a, with the structural formula ofThe yield was 89%.
1 H NMR(400MHz,d 6 -DMSO)δ2.22(s,3H),2.24(s,3H),3.76(s,2H),6.97(d,J＝7.7Hz,1H),7.05(d,J＝3.9Hz,2H),7.19(d,J＝3.5Hz,1H),7.47(d,J＝3.5Hz,1H),12.31(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ19.3,20.9,39.8,113.9,127.9,130.4,131.2,133.9,134.0,135.1,138.1,158.5,169.6.HRMS(ESI)m/z:calcd for C 13 H 14 N 2 OS(M+H) + 247.0900,found 247.0892.
Example 15
Mixing 0.6mmol of 4-chlorobenzoyl acetyl chloride, 0.6mmol of 2-aminothiazole, 0.35mmol of samarium powder and 0.6mmol of potassium hydroxide in 5mL of tetrahydrofuran, and reacting for 550s at 0 ℃ under the ultrasonic wave with the frequency of 45kHzThen sequentially filtering with diatomite, washing with ethyl acetate, distilling under reduced pressure to remove solvent, and performing rapid column chromatography purification with ethyl acetate and petroleum ether as mobile phases to obtain pure product 4b with structural formula ofThe yield was 96%.
1 H NMR(400MHz,d 6 -DMSO)δ3.78(s,2H),7.20(d,J＝3.5Hz,1H),7.35(d,J＝8.4Hz,2H),7.40(d,J＝8.4Hz,2H),7.47(d,J＝3.5Hz,1H),12.35(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ41.3,114.0,128.8,131.6,132.0,134.4,138.1,158.4,169.3.
Example 16
Mixing 0.8mmol of 4-methoxy phenylacetyl chloride, 0.8mmol of 2-aminothiazole, 0.45mmol of samarium powder and 0.8mmol of pyridine in 8mL of dichloromethane, reacting for 300s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, removing ethyl acetate and petroleum ether as mobile phase, and performing rapid column chromatography purification to obtain a pure product, namely 4c, with the structural formula ofThe yield was 95%.
1 H NMR(400MHz,d 6 -DMSO)δ3.68(s,2H),3.73(s,3H),6.89(d,J＝8.5Hz,2H),7.19(d,J＝3.5Hz,1H),7.24(d,J＝8.5Hz,2H),7.46(d,J＝3.5Hz,1H),12.27(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ41.2,55.5,113.9,114.3,127.4,130.7,138.1,158.5,158.7,169.9.
Example 17
Mixing 0.4mmol of thiophene acetyl chloride, 0.4mmol of 2-aminothiazole, 0.15mmol of samarium powder and 0.4mmol of sodium carbonate into 5mL of N, N-dimethylformamide, reacting for 150s at 25 ℃ under the ultrasonic with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing the solvent by reduced pressure distillation, purifying by using ethyl acetate and petroleum ether as a mobile phase, and performing rapid column chromatography to obtain a pure product, namely a product 4d, with the structural formula ofThe yield was 92%.
1 H NMR(400MHz,d 6 -DMSO)δ4.00(s,2H),6.97–6.99(m,2H),7.22(d,J＝3.5Hz,1H),7.41(dd,J＝4.8,1.1Hz,1H),7.48(d,J＝3.5Hz,1H),12.35(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ36.4,114.1,125.9,127.2,127.3,136.4,138.2,158.4,168.6.HRMS(ESI)m/z:calcd for C 9 H 8 N 2 OS 2 (M+H) + 225.0151,found 225.0150.
Example 18
Mixing 0.7mmol of benzoyl chloride, 0.7mmol of 2-aminothiazole, 0.45mmol of samarium powder and 0.7mmol of triethylamine in 5mL of dimethyl sulfoxide, reacting for 350s at 0 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and performing rapid column chromatography purification by taking ethyl acetate and petroleum ether as mobile phases to obtain a pure product 4e with the structural formula ofThe yield was 88%.
1 H NMR(400MHz,d 6 -DMSO)δ7.29(d,J＝3.5Hz,1H),7.48–7.57(m,3H),7.64(t,J＝7.3Hz,1H),8.10(d,J＝7.9Hz,2H),12.65(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ114.3,128.6,129.0,132.7,132.9,138.1,159.2,165.6.
Example 19
Mixing 0.6mmol of 2-naphthoyl chloride, 0.6mmol of 2-aminothiazole, 0.25mmol of samarium powder and 0.6mmol of potassium hydroxide in 6mL of ethanol, reacting for 180s at 25 ℃ under the ultrasonic with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, removing ethyl acetate and petroleum ether as mobile phases in sequence, and performing rapid column chromatography purification to obtain a pure product, namely 4f, with the structural formula ofThe yield was 79%.
1 H NMR(400MHz,d 6 -DMSO)δ7.31(d,J＝3.5Hz,1H),7.59(d,J＝3.5Hz,1H),7.62–7.70(m,2H),8.01–8.09(m,3H),8.13(d,J＝8.6Hz,1H),8.79(s,1H),12.77(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ114.3,124.8,127.5,128.2,128.7,128.8,129.6,129.7,129.9,132.5,135.1,138.1,159.3,165.7.HRMS(ESI)m/z:calcd for C 14 H 10 N 2 OS(M+H) + 255.0587,found 255.0591.
Example 20
Mixing 0.7mmol of 4-tert-butylbenzoyl chloride, 0.7mmol of 2-aminothiazole, 0.35mmol of samarium powder and 0.7mmol of potassium hydroxide in 7mL of 1, 4-dioxane, reacting for 260s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, distilling under reduced pressure to remove the solvent, removing the ethyl acetate and petroleum ether as a mobile phase, and purifying by rapid column chromatography to obtain a pure product, 4g, with the structural formula ofThe yield was 86%.
1 H NMR(400MHz,d 6 -DMSO)δ1.32(s,9H),7.28(d,J＝3.6Hz,1H),7.56(dd,J＝6.0,2.3Hz,3H),8.05(d,J＝8.3Hz,2H),12.56(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ31.3,35.2,114.2,125.9,128.5,129.8,138.1,155.9,159.2,165.3.
Example 21
Mixing 0.8mmol of furoyl chloride, 0.8mmol of 2-aminothiazole, 0.35mmol of samarium powder and 0.8mmol of potassium hydroxide in 8mL of dichloromethane, reacting for 430s at 25 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, removing ethyl acetate and petroleum ether as mobile phases, and performing rapid column chromatography purification to obtain a pure product, wherein the pure product is obtained for 4h and has the structural formula ofThe yield was 89%.
1 H NMR(400MHz,d 6 -DMSO)δ6.73–6.75(m,1H),7.27(d,J＝3.5Hz,1H),7.55(d,J＝3.6Hz,1H),7.65(d,J＝3.5Hz,1H),8.01(s,1H),12.59(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ112.7,114.3,116.8,137.9,146.2,147.6,156.4,158.6.
Example 22
Mixing 0.8mmol of 2-thiophenecarboxchloride, 0.8mmol of 2-aminothiazole, 0.48mmol of samarium powder and 0.8mmol of potassium hydroxide in 8mL of tetrahydrofuran, reacting for 600s at 40 ℃ under the ultrasonic wave with the frequency of 45kHz, then sequentially filtering with diatomite, washing with ethyl acetate, distilling under reduced pressure to remove the solvent, ethyl acetate and petroleum ether as mobile phases, and carrying out rapid column chromatography purification to obtain a pure product, namely 4i, with the structural formula ofThe yield was 87%.
1 H NMR(400MHz,d 6 -DMSO)δ7.24–7.28(m,2H),7.56(d,J＝3.6Hz,1H),7.96(d,J＝4.9Hz,1H),8.24(d,J＝3.0Hz,1H),12.74(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ114.3,129.0,131.2,133.9,137.7,137.9,159.2,160.3.
Example 23
Mixing 0.6mmol of propionyl chloride, 0.6mmol of 2-aminothiazole, 0.24mmol of samarium powder and 0.6mmol of pyridine in 5mL of tetrahydrofuran, reacting for 340s at 28 ℃ under the ultrasonic wave with the frequency of 45kHz, filtering by diatomite, washing by ethyl acetate, removing solvent by reduced pressure distillation, and performing rapid column chromatography purification by taking ethyl acetate and petroleum ether as mobile phases to obtain a pure product 4j, wherein the structural formula isThe yield thereof was found to be 97%.
1 H NMR(400MHz,d 6 -DMSO)δ1.09(t,J＝7.5Hz,3H),2.44(q,J＝7.5Hz,2H),7.16–7.18(m,1H),7.45(d,J＝3.5Hz,1H),12.03(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ9.6,28.6,113.6,137.9,158.6,172.4.
Example 24
20mmol of 4-chlorobenzoyl acetyl chloride, 20mmol of 2-aminothiazole, 10mmol of samarium powder and 20mmol of pyridine are mixed in 60mL of dichloromethane, reacted for 180s at 25 ℃ under the ultrasonic wave with the frequency of 40kHz, and then the pure product is obtained by rapid column chromatography purification by taking diatomite for filtration, ethyl acetate for washing, reduced pressure distillation to remove the solvent, ethyl acetate and petroleum ether as mobile phases, wherein the yield is 92%.
1 H NMR(400MHz,d 6 -DMSO)δ3.78(s,2H),7.20(d,J＝3.5Hz,1H),7.35(d,J＝8.4Hz,2H),7.40(d,J＝8.4Hz,2H),7.47(d,J＝3.5Hz,1H),12.35(s,1H)； 13 C NMR(100MHz,d 6 -DMSO)δ41.3,114.0,128.8,131.6,132.0,134.4,138.1,158.4,169.3.
Comparative example 1
The difference from example 1 is that no base was added and the reaction was carried out at 25℃for 1.5h under stirring, all other conditions being identical, the product obtained was 3a in 45% yield.
Comparative example 2
The difference from example 1 is that the base added is triethylamine and the reaction is carried out for 1.5h at 25℃with stirring, all other conditions being identical, the product obtained being 3a in 73% yield.
Comparative example 3
The difference from example 1 is that the reaction is carried out for 1.5h at 25℃with stirring, the other conditions being identical, the product obtained being 3a in 86% yield.
Comparative example 4
The difference from example 1 is that the base added is potassium hydroxide and reacted at 25℃for 1.5h with stirring, all other conditions being identical, the product obtained is 3a in 65% yield.
Comparative example 5
The difference from example 1 is that the base added is sodium carbonate and the reaction is carried out for 1.5h at 25℃with stirring, the other conditions being the same, the product obtained being 3a with a yield of 82%.
Comparative example 6
The difference from example 1 is that the base added is potassium carbonate and the reaction is carried out for 1.5h at 25℃with stirring, all other conditions being identical, the product obtained is 3a with a yield of 62%.
Comparative example 7
The difference from example 1 is that the added base is sodium hydroxide and the reaction is carried out for 1.5h at 25℃with stirring, the other conditions being the same, the product obtained being 3a with a yield of 67%.
Comparative example 8
The difference from example 1 is that the samarium powder was used in an amount of 0.15mmol, and reacted at 25℃for 1.5 hours under stirring under the same conditions, to give a product of 3a in 79% yield.
Comparative example 9
The difference from example 1 is that the samarium powder was used in an amount of 0.05mmol, and reacted at 25℃for 1.5 hours under stirring under the same conditions, to give a product of 3a in a yield of 68%.
Comparative example 10
The difference from example 1 was that samarium powder was not added, and the reaction was carried out at 25℃for 1.5 hours under stirring under the same conditions, to obtain 3a as a product in 52% yield.
Comparative example 11
The difference from example 1 was that the samarium powder was used in an amount of 0.3mmol, and reacted at 25℃for 1.5 hours under stirring under the same conditions, to give a product of 3a in a yield of 87%.
By comparing example 1 with the comparative example, it can be found that the addition amount of samarium powder and different kinds of alkali affect the yield of the product, and the highest yield of the product can be ensured under the combined action of ultrasonic conditions and samarium powder.
Comparative example 12
The difference from example 14 is that 4-nitrobenzoyl chloride is reacted with 2-aminothiazole under the same conditions, and the corresponding amide compound is not obtained.
Comparative example 13
The difference from example 14 is that 2,4, 6-trimethylbenzoyl chloride is reacted with 2-aminothiazole under the same conditions, and only a trace amount of the amide compound is obtained.
From the above examples, the present invention provides a process for producing (benzo) thiazole amide compounds, which comprises mixing a substituted acyl chloride, compound 1 or compound 2, samarium powder and a base in a solvent, and reacting under ultrasound to obtain (benzo) thiazole amide compounds. The method has the advantages of simple operation, low cost, high product yield, wide substrate application range and the like in the preparation of the (benzo) thiazole amide compound.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims (9)

1. A process for the preparation of a (benzo) thiazole amide containing compound comprising the steps of: mixing substituted acyl chloride, a compound 1 or a compound 2, samarium powder and alkali in a solvent, and reacting under ultrasonic to obtain a (benzo) thiazole amide compound;
the structural formula of the substituted acyl chloride isWherein R is 1 Is benzyl, alkyl, aryl or heteroaryl;
the structural formula of the compound 1 isWherein R is 2 And R is 3 Independently chlorine, bromine, nitro, methoxy, methyl or hydrogen; the structural formula of the compound 2 is +.>Wherein R is 4 And R is 5 Independently methyl, bromo or nitro.
2. The method according to claim 1, wherein the substituted acyl chloride is phenylacetyl chloride, 2, 5-dimethylbenzene acetyl chloride, 4-chlorobenzoyl chloride, 4-methoxyphenylacetyl chloride, thiophenyl acetyl chloride, benzoyl chloride, 2-naphthoyl chloride, 4-t-butylbenzoyl chloride, furoyl chloride, 2-thiophenyl formyl chloride or propionyl chloride.
3. The preparation method according to claim 1 or 2, wherein the compound 1 is 2-aminothiazole, 2-amino-5-methylthiazole, 2-amino-4-methylthiazole, 2-amino-5-nitrothiazole or 2-amino-5-bromothiazole.
4. The preparation method according to claim 1 or 2, wherein the compound 2 is 2-amino-6-chlorobenzothiazole, 2-aminobenzothiazole, 2-amino-6-fluorobenzothiazole, 2-amino-6-bromobenzothiazole, 2-amino-6-nitrobenzothiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole or 2-amino-4-methylbenzothiazole.
5. The method according to claim 2, wherein the base comprises one or more of triethylamine, pyridine, potassium hydroxide, sodium carbonate and potassium carbonate.
6. The method according to claim 1, 2 or 5, wherein the solvent comprises one or more of tetrahydrofuran, ethanol, acetonitrile, 1, 4-dioxane, ethyl acetate, dichloromethane, N-dimethylformamide and dimethylsulfoxide.
7. The preparation method according to claim 6, wherein the molar volume ratio of the substituted acyl chloride, the compound 1 or the compound 2, the samarium powder, the base and the solvent is 0.4 to 0.8mmol:0.4 to 0.8mmol:0.04 to 0.48mmol:0.4 to 0.8mmol: 1-8 mL.
8. The method according to claim 5 or 7, wherein the frequency of the ultrasound is 40 to 50kHz.
9. The method according to claim 8, wherein the reaction is carried out at a temperature of 0 to 40 ℃ for a time of 15 to 600 seconds.
CN202311086798.1A 2023-08-28 2023-08-28 Preparation method of (benzo) thiazole amide-containing compound Pending CN117126119A (en)

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