CN110128413B - 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof - Google Patents

5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof Download PDF

Info

Publication number
CN110128413B
CN110128413B CN201910496535.5A CN201910496535A CN110128413B CN 110128413 B CN110128413 B CN 110128413B CN 201910496535 A CN201910496535 A CN 201910496535A CN 110128413 B CN110128413 B CN 110128413B
Authority
CN
China
Prior art keywords
reaction
acetyl
methyl
eutectic solvent
dihydropyrimidine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201910496535.5A
Other languages
Chinese (zh)
Other versions
CN110128413A (en
Inventor
刘玉婷
杨岚
尹大伟
党阳
邹倩
李洁
孙嘉希
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shaanxi University of Science and Technology
Original Assignee
Shaanxi University of Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shaanxi University of Science and Technology filed Critical Shaanxi University of Science and Technology
Priority to CN201910496535.5A priority Critical patent/CN110128413B/en
Publication of CN110128413A publication Critical patent/CN110128413A/en
Application granted granted Critical
Publication of CN110128413B publication Critical patent/CN110128413B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)

Abstract

Adding A mol of choline chloride and B mol of methanesulfonic acid into a dry three-neck flask, stirring at room temperature to prepare a eutectic solvent, then adding C mol of 3-formyl-9-alkyl carbazole, D mol of urea and E mol of acetylacetone, carrying out reaction in a water bath at 50 ℃, and monitoring by TLC until the reaction is complete. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The method has the advantages of simple operation, high yield, high product purity, short reaction time, recyclable eutectic solvent, environmental protection and low cost, and has important significance for the synthesis and development of the compounds.

Description

5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a preparation method of 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone.
Background
Dihydropyrimidinones are a very important class of nitrogen-containing heterocyclic compounds, and research shows that the dihydropyrimidinones have the exploration potential in biology, pharmacology and materials science. Of which the most important is as a pharmaceutical intermediate. Dihydropyrimidinones can be used as a lead for developing anticancer drugs, urease inhibitors, antimalarials, calcium channel antagonists and the like, and have antiviral, antifungal, antitumor, anti-inflammatory and other effects. Because of its wide application prospect, the synthesis of dihydropyrimidinones has attracted great attention from researchers.
The synthesis of dihydropyrimidinones by the Biginelli reaction is currently the predominant method. The traditional synthesis method has low yield and long reaction time, and a plurality of new technologies are also applied to the synthesis, such as microwave and ultrasonic assisted reaction, and the yield can be improved by using novel catalysts such as heteropoly acid, ionic liquid, high molecular nano material and the like, but the problems of harsh reaction conditions, expensive catalyst, high toxicity and the like exist. Therefore, the method for preparing the 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone with simple operation, high yield, environmental protection, high product purity and short reaction time has certain significance.
Disclosure of Invention
The invention aims to provide a preparation method for preparing 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone, which has the advantages of simple operation, high yield, high product purity, short reaction time, recyclable eutectic solvent, environmental protection and low cost.
In order to achieve the purpose, the invention adopts the technical scheme that:
the structural general formula of the 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone is as follows:
Figure BDA0002088793470000021
wherein R is CH3，C2H5，C3H7-n，C4H9-n,C12H25-n，C14H29-n，C16H33-n,
Figure BDA0002088793470000022
The preparation method of 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone comprises the following steps:
adding A mol of choline chloride and B mol of methanesulfonic acid into a dry three-neck flask, stirring at room temperature to obtain a eutectic solvent, then adding C mol of 3-formyl-9-alkyl carbazole, D mol of urea and E mol of acetylacetone, wherein A: B is 1:2, C: D: E is 1:0.7:1.1, carrying out reaction in a water bath at 50 ℃, and monitoring by TLC until the reaction is complete. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone.
The general structural formula of the 3-formyl-9-alkyl carbazole is as follows:
Figure BDA0002088793470000031
wherein R is CH3，C2H5，C3H7-n，C4H9-n,C12H25-n，C14H29-n，C16H33-n,
Figure BDA0002088793470000032
The TLC is used for monitoring, and the developing solvent is a mixed solution of dichloromethane and methanol in a volume ratio of 30: 1.
Compared with the prior art, the invention has the beneficial effects that:
the preparation method of 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone provided by the invention takes 3-formyl-9-alkyl carbazole, urea and acetylacetone as raw materials, and takes a eutectic solvent choline chloride-methanesulfonic acid as a solvent and a catalyst, so that the 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone can be prepared with high yield. The method has the advantages of simple operation, high yield, high product purity, short reaction time, recyclable eutectic solvent, environmental protection, low cost and great application prospect.
The eutectic solvent is used as a novel catalyst and solvent in the synthesis process of the target compound, the catalytic effect is superior to that of the traditional catalyst, the use of the solvent is reduced, the eutectic solvent can be recycled after use, and the eutectic solvent has the advantages of high efficiency and environmental protection.
The synthesized target compound 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone has wide application prospect in the aspect of being used as an intermediate of anticancer, antiviral, antifungal drugs and the like.
Drawings
FIG. 1 is an IR spectrum of 5-acetyl-4- (N-methylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 1;
FIG. 2 is an IR spectrum of 5-acetyl-4- (N-ethylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 2;
FIG. 3 is an IR spectrum of 5-acetyl-4- (N-propylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 3;
FIG. 4 is an IR spectrum of 5-acetyl-4- (N-butylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 4;
FIG. 5 is an IR spectrum of 5-acetyl-4- (N-benzylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 5;
FIG. 6 is an IR spectrum of 5-acetyl-4- (N-dodecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 6;
FIG. 7 is an IR spectrum of 5-acetyl-4- (N-tetradecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 7;
FIG. 8 is an IR spectrum of 5-acetyl-4- (N-hexadecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 8;
FIG. 9 is a drawing of 5-acetyl-4- (N-methylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 11H NMR spectrum;
FIG. 10 is a drawing of 5-acetyl-4- (N-ethylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 21H NMR spectrum;
FIG. 11 is a drawing of 5-acetyl-4- (N-propylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 31H NMR spectrum;
FIG. 12 is a drawing of 5-acetyl-4- (N-butylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 41H NMR spectrum;
FIG. 13 is a drawing of 5-acetyl-4- (N-benzylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 51H NMR spectrum;
FIG. 14 is a drawing of 5-acetyl-4- (N-dodecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 61H NMR spectrum;
FIG. 15 is 5-ethane prepared in example 7Process for preparing acyl-4- (N-tetradecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one1H NMR spectrum;
FIG. 16 is a drawing of 5-acetyl-4- (N-hexadecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 81H NMR spectrum;
FIG. 17 is a drawing of 5-acetyl-4- (N-methylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 113C NMR spectrum;
FIG. 18 is a drawing of 5-acetyl-4- (N-ethylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 213C NMR spectrum;
FIG. 19 is a drawing of 5-acetyl-4- (N-propylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 313C NMR spectrum;
FIG. 20 is a drawing of 5-acetyl-4- (N-butylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 413C NMR spectrum;
FIG. 21 is a drawing of 5-acetyl-4- (N-benzylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 513C NMR spectrum;
FIG. 22 is a drawing of 5-acetyl-4- (N-dodecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 613C NMR spectrum;
FIG. 23 is a drawing of 5-acetyl-4- (N-tetradecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 713C NMR spectrum;
FIG. 24 is a drawing of 5-acetyl-4- (N-hexadecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one prepared in example 813C NMR spectrum.
Detailed Description
The following is a further detailed description of the invention with reference to examples:
the invention takes 3-formyl-9-alkyl carbazole, urea and acetylacetone as raw materials, and takes a eutectic solvent choline chloride-methanesulfonic acid as a solvent and a catalyst to prepare a series of 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The reaction equation is as follows:
Figure BDA0002088793470000061
wherein R is CH3，C2H5，C3H7-n，C4H9-n,C12H25-n，C14H29-n，C16H33-n,
Figure BDA0002088793470000062
Example 15 preparation of acetyl-4- (N-methylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one:
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.04g (5mmol) of 3-formyl-9-methylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with absolute ethyl alcohol to obtain pure yellow solid 5-acetyl-4- (N-methylcarbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 89.1%, and the melting point is 120.0-123.0 ℃.
IR(KBr,ν/cm-1):3395(νN-H),3043,3013(νC＝C-H),2923(νasC-H,-CH3),2852(ν-CH),1656(νC＝O),1588,1473(ν-C＝C,Ar),1370(δs-CH3),1319(νAr-N),1248(νC-N),803,746(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.50(s,1H,N-H),8.20(d,1H,N-H),7.97(d,1H,Ar-H),7.81(d,1H,Ar-H),7.63(m,2H,Ar-H),7.53-7.48(m,1H,Ar-H),7.26(t,1H,Ar-H),7.02(d,1H,Ar-H),6.51(s,1H,C-H),3.90(s,3H,-CH3),2.24(s,3H,-CH3),1.22(s,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):157.46,141.59,141.20,139.86,126.31,125.88,122.51,122.02,120.56,120.48,119.48,109.74,109.59 101.27,29.20,13.96.
EXAMPLE 25 preparation of acetyl-4- (N-ethylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.11g (5mmol) of 3-formyl-9-ethylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with absolute ethyl alcohol to obtain pure yellow solid 5-acetyl-4- (N-ethyl carbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 89.0%, and the melting point is 109.0-112.0 ℃.
IR(KBr,ν/cm-1):3431(νN-H),3044,3014(νC＝C-H),2920(νasC-H,-CH3),2850(ν-CH),1646(νC＝O),1587,1468,1438(ν-C＝C,Ar),1332(νAr-N),861,804,747(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):δppm 8.50(s,1H,N-H),8.20(d,1H,N-H),7.97(d,1H,Ar-H),7.80(d,1H,Ar-H),7.63(m,2H,Ar-H),7.48(m,1H,Ar-H),7.24(m,1H,Ar-H),7.01(d,1H,Ar-H),6.52(s,1H,C-H),4.48-4.40(m,3H,-CH3),2.26(d,3H,-CH3),2.06(s,2H,-CH2),1.32(t,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):δppm 157.53,140.59,140.15,126.37,126.16,125.92,122.74 122.25,120.74,120.67,109.73,109.59,109.47,69.86,37.25,31.34,22.15,13.80.
EXAMPLE 35 preparation of acetyl-4- (N-propylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.19g (5mmol) of 3-formyl-9-propylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure red yellow solid 5-acetyl-4- (N-propylcarbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 88.2%, and the melting point is 133.0-135.0 ℃.
IR(KBr,ν/cm-1):3471(νN-H),3121,3051(νC＝C-H),2958(νasC-H,-CH3),2924(νasC-H,-CH2),2853(νsC-H,-CH2),1659(νC＝O),1591,1542,1465(ν-C＝C,Ar),1384(δs-CH3),1348(νAr-N),1224(νC-N),872,804,747(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.50(s,1H,N-H),8.20(d,1H,N-H),7.97(d,1H,Ar-H),7.79(d,1H,Ar-H),7.68-7.60(m,2H,Ar-H),7.49(d,1H,Ar-H),7.24(t,1H,Ar-H),7.02(d,1H,Ar-H),6.52(s,1H,-CH),4.44-4.34(m,2H,-CH2),2.24(s,2H,-CH2),1.80(m,3H,-CH3),1.20(s,3H,-CH3),0.86(t,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):174.46,157.50,141.14,140.67,126.28,125.84,122.55,122.09,121.93,120.65,120.56,119.42,109.95,109.80,101.29,69.82,43.91,22.13,21.93,13.98,11.37.
EXAMPLE 45 preparation of acetyl-4- (N-butylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.26g (5mmol) of 3-formyl-9-butylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure red yellow solid 5-acetyl-4- (N-butylcarbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 88.3 percent, and the melting point is 117.0-120.0 ℃.
IR(KBr,ν/cm-1):3471,3368(νN-H),3111,3081(νC＝C-H),2961(νasC-H,-CH3),2926(νasC-H,N-CH2),2874(νsC-H,-CH2),1693(νC＝O),1598,1543,1452(νC＝C,Ar),1386(δS-CH3),1354(νAr-N),1252(νC-N),873,805,755(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.50(s,1H,N-H),8.20(d,1H,N-H),7.97(d,1H,Ar-H),7.79(d,1H,Ar-H),7.68-7.60(m,2H,Ar-H),7.48(t,1H,Ar-H),7.25(t,1H,Ar-H),7.01(d,1H,Ar-H),6.52(s,1H,-CH),4.41(t,2H,-CH2),2.24(s,2H,-CH2),1.82-1.64(m,3H,-CH3),1.29(m,3H,-CH3),1.21(s,2H,-CH2),0.87(t,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):157.49,141.04,140.59,126.29,125.85,122.58,122.10,120.65,120.58,119.42,109.90,109.76,101.29,69.82,42.25,30.76,22.13,19.81,13.99,13.76.
EXAMPLE 55 preparation of acetyl-4- (N-benzylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.43g (5mmol) of 3-formyl-9-benzylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with absolute ethyl alcohol to obtain pure yellow solid 5-acetyl-4- (N-benzyl carbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 85.0 percent, and the melting point is 103.0-106.0 ℃.
IR(KBr,ν/cm-1):3394(νN-H),3057,3026(νC＝C-H),2923(νasC-H,-CH3),2852(ν-CH),1662(νC＝O),1613(νC＝C),1593,1493,1466(ν-C＝C,Ar),1330(νAr-N),890,818,748(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.53(s,1H,N-H),8.23(d,1H,N-H),7.96(d,1H,Ar-H),7.78(d,1H,Ar-H),7.73-7.60(m,3H,Ar-H),7.47(t,1H,Ar-H),7.29-7.24(m,3H,Ar-H),7.18(d,3H,Ar-H),6.52(s,1H,C-H),5.69(s,2H,-CH2),2.24(s,3H,-CH3),1.15(s,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):140.76,137.57,129.72,128.70,127.43,126.81,126.50,122.83,120.68,110.19,69.84,33.75,22.14,14.00.
EXAMPLE 65 preparation of acetyl-4- (N-dodecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.82g (5mmol) of 3-formyl-9-dodecyl carbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with absolute ethyl alcohol to obtain pure yellow solid 5-acetyl-4- (N-dodecyl carbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 87.0 percent, and the melting point is 100.0-103.0 ℃.
IR(KBr,ν/cm-1):3466,3366(νN-H),3122,3050(νC＝C-H),2923(νasC-H,-CH2),2851(νsC-H,-CH2),1651(νC＝O),1590,1464(ν-C＝C,Ar),1384(δs-CH3),1350(νAr-N),1234(νC-N),871,803,745(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.47(s,1H,N-H),8.17(d,1H,N-H),7.96(d,1H,Ar-H),7.76(d,1H,Ar-H),7.60-7.54(m,2H,Ar-H),7.44(t,1H,Ar-H),7.22(t,1H,Ar-H),7.00(d,1H,Ar-H),6.50(s,1H,C-H),4.34(t,2H,-CH2),2.23(s,2H,-CH2),1.70(d,3H,-CH3),1.15(d,20H,-C10H20),1.09(s,3H,-CH3),0.79(s,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):157.51,141.02,140.56,139.84,126.27,126.20,125.75,122.58,122.12,120.65,120.52,119.36,109.80,109.66,101.27,69.82,42.42,31.31,28.99,28.90,28.76,28.71,28.50,26.42,22.11,13.93.
EXAMPLE 75 preparation of acetyl-4- (N-tetradecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 1.96g (5mmol) of 3-formyl-9-tetradecylcarbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure yellow solid 5-acetyl-4- (N-tetradecylcarbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 85.5 percent, and the melting point is 73.0-75.0 ℃.
IR(KBr,ν/cm-1):3463,3396(νN-H),3047,3016(νC＝C-H),2921(νasC-H,-CH3),2849(ν-CH),1659(νC＝O),1616(νC＝C),1591,1465(ν-C＝C,Ar),1328(νAr-N),862,799,739(γC-H,Ar-R)；
1H NMR(400MHz,DMSO-d6,δ,ppm):8.48(s,1H,N-H),8.19(d,1H,N-H),7.96(d,1H,Ar-H),7.78(d,1H,Ar-H),7.68-7.54(m,2H,Ar-H),7.47(s,1H,Ar-H),7.24(s,1H,Ar-H),7.00(d,1H,Ar-H),6.51(s,1H,C-H),4.38(s,2H,-CH2),2.24(s,3H,-CH3),1.75(s,3H,-CH3),1.25-1.11(m,24H,-C12H24),0.82(s,3H,-CH3)；
13C NMR(101MHz,DMSO-d6,δ,ppm):157.46,141.02,140.57,139.80,126.27,126.21,125.76,122.56,122.09,120.59,119.36,109.83,109.69,101.21,69.80,42.42,31.28,28.99,28.92,28.84,28.69,28.57,28.45,26.37,22.08,13.92.
EXAMPLE 85 preparation of acetyl-4- (N-hexadecylcarbazole) -6-methyl-3, 4-dihydropyrimidin-2 (1H) -one
1.4g (10mmol) of choline chloride and 1.92(20mmol) of methanesulfonic acid are added into a dry three-neck flask, the mixture is stirred at room temperature to prepare a eutectic solvent, then 2.10g (5mmol) of 3-formyl-9-hexadecyl carbazole, 0.35g (5.5mol) of urea and 0.55g (5.5mmol) of acetylacetone are added, the reaction is carried out in a water bath at 50 ℃, and TLC monitoring is carried out until the reaction is completed. After the reaction is finished, pouring the reaction liquid into water to separate out solid, carrying out suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain the eutectic solvent again. Recrystallizing the crude product with anhydrous ethanol to obtain pure yellow solid 5-acetyl-4- (N-hexadecyl carbazole) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone. The yield is 85.1 percent, and the melting point is 67.0-69.0 ℃.
IR(KBr,ν/cm-1):3396,3301(νN-H),3045,3015(νC＝C-H),2920(νasC-H,-CH3),2849(ν-CH),1663(νC＝O),1616(νC＝C),1592,1465(νC＝C,Ar),1328(νAr-N),861,799,737(γC-H,Ar-R).
1H NMR(400MHz,DMSO-d6,δ,ppm):8.49(s,1H,N-H),8.20(d,1H,N-H),7.96(m,1H,Ar-H),7.78(s,1H,Ar-H),7.62(d,2H,Ar-H),7.54-7.43(m,2H,Ar-H),7.24(d,1H,Ar-H),7.01(d,1H,Ar-H),6.51(d,1H,C-H),4.40(d,2H,-CH2),2.24(d,3H,-CH3),1.75(s,3H,-CH3),1.17(d,28H,-C14H28),0.83(d,3H,-CH3).
13C NMR(101 MHz,DMSO-d6,δ,ppm):157.47,141.02,140.58,129.65,126.23,125.81,122.55,122.11,120.56,119.38,109.87,101.20,42.43,31.29,29.03,28.84,28.70,28.46,26.39,22.10,13.95.

Claims (3)

1. A preparation method of 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone is characterized by comprising the following steps:
reacting 3-formyl-9-alkyl carbazole, urea and acetylacetone in a choline chloride-methanesulfonic acid-containing eutectic solvent at 50 ℃ to obtain 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -one; the mol ratio of the choline chloride, the methanesulfonic acid, the 3-formyl-9-alkyl carbazole to the urea to the acetylacetone is 10 mmol: 20 mmol: 5 mmol: 5.5 mol: 5.5 mmol;
the structural general formula of the 3-formyl-9-alkyl carbazole is shown as follows:
Figure 799099DEST_PATH_IMAGE002
（Ⅰ）；
wherein R is: -CH3，-C2H5，-C3H7-n，-C4H9-n, -C12H25-n，-C14H29-n，-C16H33-n,
Figure 919502DEST_PATH_IMAGE004
。
2. The method according to claim 1, characterized in that the specific steps comprise:
adding choline chloride and methanesulfonic acid into a dry three-neck flask, stirring at room temperature to prepare a eutectic solvent, and then adding 3-formyl-9-alkyl carbazole, urea and acetylacetone; carrying out reaction in a water bath at 50 ℃, and monitoring by TLC until the reaction is complete; after the reaction is finished, pouring the reaction solution into water to separate out solid, performing suction filtration, washing and drying to obtain a crude product, and recovering the filtrate to obtain a eutectic solvent again; recrystallizing the crude product with anhydrous ethanol to obtain pure 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone.
3. The method of claim 2, wherein the TLC is used for monitoring the reaction, the reaction is completed when the starting material point disappears, and the developing agent of the TLC is a mixed solution of dichloromethane and methanol in a volume ratio of 30: 1.
CN201910496535.5A 2019-06-10 2019-06-10 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof Active CN110128413B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910496535.5A CN110128413B (en) 2019-06-10 2019-06-10 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910496535.5A CN110128413B (en) 2019-06-10 2019-06-10 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof

Publications (2)

Publication Number Publication Date
CN110128413A CN110128413A (en) 2019-08-16
CN110128413B true CN110128413B (en) 2022-03-25

Family

ID=67580836

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910496535.5A Active CN110128413B (en) 2019-06-10 2019-06-10 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof

Country Status (1)

Country Link
CN (1) CN110128413B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111217862B (en) * 2020-02-26 2023-01-31 陕西科技大学 Preparation method of 4-aryl-6-ferrocenyl-3, 4-dihydropyrimidine-2 (1H) -ketone

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005037799A1 (en) * 2003-10-16 2005-04-28 Cytokinetics, Inc. Compounds, compositions, and methods
CN107935996B (en) * 2017-11-30 2020-04-07 陕西科技大学 3, 4-dihydropyrimidine-2 (1H) - (sulfur) ketone compounds and preparation method thereof
CN108059616B (en) * 2018-02-13 2020-01-17 大连大学 Synthesis method of 3, 4-dihydropyrimidine-2 (1H) -thioketone
CN108129399B (en) * 2018-02-13 2020-01-17 大连大学 Synthesis method of 4-aryl-5-methoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone
CN108129398B (en) * 2018-02-13 2020-01-17 大连大学 Synthesis method of 4-halogenated phenyl-5-ethoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -ketone

Also Published As

Publication number Publication date
CN110128413A (en) 2019-08-16

Similar Documents

Publication Publication Date Title
CN110128413B (en) 5-acetyl-4- (N-substituted carbazolyl) -6-methyl-3, 4-dihydropyrimidine-2-ketone and preparation method thereof
CN111333543B (en) Synthesis method of rilpivirine intermediate
CN105330560A (en) Enzalutamide intermediate preparation method
CN111349045A (en) Synthetic method of lenvatinib and novel intermediate
CN110551123A (en) Preparation method of 5- (tert-butyloxycarbonyl) -2-methyl-4, 5,6, 7-tetrahydro-2H-pyrazolo [4,3-C ] pyridine-7-carboxylic acid
CN111233745B (en) (E)1- (9-alkyl-carbazole-3-) -acrylic acid and preparation method thereof
CN107935996A (en) A kind of 3,4 dihydro-pyrimidin 2 (1H) (sulphur) ketone compounds and preparation method thereof
CN111217862B (en) Preparation method of 4-aryl-6-ferrocenyl-3, 4-dihydropyrimidine-2 (1H) -ketone
CN110003089B (en) 3-hydroxymethyl-9-substituted carbazole and preparation method thereof
RO121211B1 (en) Process for preparing 4-(heteroaryl-methyl)-1(2h)phthalazinones
CN103360339A (en) Green method for catalytically synthesizing 2'-aminobenzothiazolyl-arylmethyl-2-naphthol
WO2022011948A1 (en) Preparation method for vortioxetine
CN112125889A (en) Preparation method of 7-bromo-2- (1-methyl-1H-pyrazol-4-yl) quinoxaline
CN109776435B (en) Method for preparing 1,2, 3-triazole by dibromovinylbenzene one-pot method
CN112574106B (en) Synthesis method of 7-amino-5-bromoquinoline
CN110590641B (en) Green preparation method of 3-hydroxyisoindole-1-ketone series compounds
CN107759483B (en) Preparation method of methylamino-substituted alkyl cyclopentanecarboxylate
CN111484458B (en) Preparation method of 2-hydroxy-5-sulfonic pyrimidine
CN109053513B (en) Substituted naphthol compound and application thereof in antitumor drugs
CN113698407B (en) Method for preparing indazole [3,2-b ] quinazolin-7 (5H) -one derivative based on Ullmann coupling reaction
CN115108980B (en) Preparation method of No. 4 acylated derivative of 2-methylquinoline compound
CN113956209B (en) Preparation method of NH-1,2, 3-triazole compound
CN113717100B (en) Preparation method of pefloxacin aldehyde 4-aryl thiosemicarbazide derivative
CN109867633B (en) Method for synthesizing 1,2, 3-triazole from beta-bromostyrene
CN110452133A (en) A kind of preparation method of diazanyl phthalic acid methyl ester derivative

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant