CN116162039A - Synthesis method of visible light mediated butanediamide compound - Google Patents
Synthesis method of visible light mediated butanediamide compound Download PDFInfo
- Publication number
- CN116162039A CN116162039A CN202310145190.5A CN202310145190A CN116162039A CN 116162039 A CN116162039 A CN 116162039A CN 202310145190 A CN202310145190 A CN 202310145190A CN 116162039 A CN116162039 A CN 116162039A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- butanediamide
- mmol
- target product
- 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.)
- Pending
Links
- -1 butanediamide compound Chemical class 0.000 title claims abstract description 38
- 230000001404 mediated effect Effects 0.000 title claims abstract description 12
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 144
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 66
- 239000012074 organic phase Substances 0.000 claims description 42
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical group C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims description 22
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- 238000004440 column chromatography Methods 0.000 claims description 22
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 claims description 22
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 claims description 22
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 claims description 22
- 238000010791 quenching Methods 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 238000000926 separation method Methods 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000007787 solid Substances 0.000 description 32
- BPCNEKWROYSOLT-UHFFFAOYSA-N n-phenylprop-2-enamide Chemical compound C=CC(=O)NC1=CC=CC=C1 BPCNEKWROYSOLT-UHFFFAOYSA-N 0.000 description 20
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 20
- 238000000605 extraction Methods 0.000 description 11
- 238000004949 mass spectrometry Methods 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 11
- 238000001035 drying Methods 0.000 description 10
- JUFNMMKBIRXISE-UHFFFAOYSA-N 2-(hexylamino)-2-oxoacetic acid Chemical compound CCCCCCNC(=O)C(O)=O JUFNMMKBIRXISE-UHFFFAOYSA-N 0.000 description 9
- RULNGIPWAOXQFQ-UHFFFAOYSA-N n-(2-methylphenyl)prop-2-enamide Chemical compound CC1=CC=CC=C1NC(=O)C=C RULNGIPWAOXQFQ-UHFFFAOYSA-N 0.000 description 4
- STSOUDHGAHKGPV-UHFFFAOYSA-N n-(3,5-dimethylphenyl)prop-2-enamide Chemical compound CC1=CC(C)=CC(NC(=O)C=C)=C1 STSOUDHGAHKGPV-UHFFFAOYSA-N 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical class NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- RTMHPLCGCWUMFG-UHFFFAOYSA-N n-(2-chlorophenyl)prop-2-enamide Chemical compound ClC1=CC=CC=C1NC(=O)C=C RTMHPLCGCWUMFG-UHFFFAOYSA-N 0.000 description 2
- WOPYVIUYYYYHTG-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)prop-2-enamide Chemical compound COC1=CC(NC(=O)C=C)=CC(OC)=C1 WOPYVIUYYYYHTG-UHFFFAOYSA-N 0.000 description 2
- PAJMSUNTWHMLKC-UHFFFAOYSA-N n-(3-bromophenyl)prop-2-enamide Chemical compound BrC1=CC=CC(NC(=O)C=C)=C1 PAJMSUNTWHMLKC-UHFFFAOYSA-N 0.000 description 2
- NZXQEWMZAUGCLB-UHFFFAOYSA-N n-(3-chlorophenyl)prop-2-enamide Chemical compound ClC1=CC=CC(NC(=O)C=C)=C1 NZXQEWMZAUGCLB-UHFFFAOYSA-N 0.000 description 2
- QJFFMEYVPAZRQF-UHFFFAOYSA-N n-(4-ethylphenyl)prop-2-enamide Chemical compound CCC1=CC=C(NC(=O)C=C)C=C1 QJFFMEYVPAZRQF-UHFFFAOYSA-N 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- GUZSZEGZZYGNJR-UHFFFAOYSA-N 2-(benzylamino)-2-oxoacetic acid Chemical compound OC(=O)C(=O)NCC1=CC=CC=C1 GUZSZEGZZYGNJR-UHFFFAOYSA-N 0.000 description 1
- OBIXFICISBRHCR-UHFFFAOYSA-N 2-(butylamino)-2-oxoacetic acid Chemical compound CCCCNC(=O)C(O)=O OBIXFICISBRHCR-UHFFFAOYSA-N 0.000 description 1
- BPCATNGVUSFCNY-UHFFFAOYSA-N 2-(tert-butylamino)-2-oxoacetic acid Chemical compound CC(C)(C)NC(=O)C(O)=O BPCATNGVUSFCNY-UHFFFAOYSA-N 0.000 description 1
- MRBFRUTXRPPRJK-UHFFFAOYSA-N 2-oxo-2-(2-phenylpropan-2-ylamino)acetic acid Chemical compound OC(=O)C(=O)NC(C)(C)C1=CC=CC=C1 MRBFRUTXRPPRJK-UHFFFAOYSA-N 0.000 description 1
- 102000052052 Casein Kinase II Human genes 0.000 description 1
- 108010010919 Casein Kinase II Proteins 0.000 description 1
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of a visible light mediated butanediamide compound, which comprises the following specific processes: the N-substituted acrylamide compound and the oxamide acid compound are placed in a solvent, and react under the action of a catalyst and alkali under the condition of blue light irradiation and nitrogen environment, and the target product of the butanediamide compound is obtained through separation after the reaction is finished. The synthesis method disclosed by the invention uses more green and clean visible light as energy, and has the advantages of simple and easily obtained raw materials and higher product yield.
Description
Technical Field
The invention belongs to the technical field of synthesis of butanediamide compounds, and particularly relates to a synthesis method of a visible light mediated butanediamide compound.
Background
Butanediamide is widely used as a linking group in pharmaceutical research and development, for example, in bivalent protein kinase CK2 inhibitors KN2 (j.med.chem.2022, 65, 1302-1312.). There are studies showing that it can be applied as a linking group in the development of small molecule PD-1/PDL1 inhibitors (European Journal of Medicinal chemistry2020,199, 112377). Thus, the construction of succinamide compounds, in particular derivatives with different groups attached, is of great importance for pharmaceutical development and organic synthetic chemistry. The common method is to connect the single-protected succinic acid serving as a raw material with the first amine by adopting an amide condensation reaction, and then connect the single-protected succinic acid with the second amine by adopting the condensation reaction after removing the protecting group (J.Med. Chem.2022,65, 1302-1312.).
Disclosure of Invention
The invention solves the technical problem of providing a synthesis method of the butanediamide compound mediated by visible light, which has simple process and low cost, and the method uses more green and clean visible light as energy, so that the raw materials are simple and easy to obtain, and the product yield is higher.
The invention adopts the following technical proposal to solve the technical problems, and is characterized in that the method for synthesizing the butanediamide compound mediated by visible light is characterized by comprising the following specific processes: placing an N-substituted acrylamide compound and an oxamide acid compound in a solvent, reacting under the action of a catalyst and alkali and under the condition of blue light irradiation and nitrogen environment, and separating after the reaction is finished to obtain a target product of the butanediamide compound; the catalyst is 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile, the alkali is lithium hydroxide monohydrate, the structure of the N-substituted acrylamide compound is shown in a formula A, the structure of the oxamide compound is shown in a formula B, and the structure of the butanediamide compound is shown in a formula C:
r in formula A and formula C 1 H, cl, br, C of a shape of H, cl, br, C 1-5 Alkyl or C 1-5 Alkoxy, R 1 The substitution on the benzene ring being mono-or di-substituted, R in formulae B and C 2 Is C 1-5 Alkyl, adamantyl, phenyl C 1-5 Alkyl or ester-containing alkyl.
Further defined, the molar ratio of the N-substituted acrylamide compound to the oxamide compound to the catalyst to the alkali is 1:1-3:0.01-0.1:1-3.
Further defined, the solvent is anhydrous N, N-dimethylacetamide.
Further limited, the blue light source is a blue LED lamp, the wavelength of which is 450-460 nm, and the power of which is 5-10W.
Further limited, the reaction temperature in the reaction process is 25-40 ℃ and the reaction time is 6-24 h.
Further limiting, adding saturated NaCl solution into the reaction solution after the reaction is finished to quench the reaction, extracting the reaction solution with ethyl acetate for three times, combining organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain the target compound succinamide compounds.
Compared with the prior art, the invention has the following advantages and beneficial effects: the method has the advantages of simple and safe operation, mild reaction conditions, cheap and easily obtained raw materials, light source of the method is visible light, green and pollution-free, the catalyst is relatively friendly to the environment, and the method has higher yield of the synthesized target product, better functional group tolerance and substrate application range, can be used for later modification of medicines, and is expected to be applied to medicine research and development.
Detailed Description
The above-described matters of the present invention will be described in further detail by way of examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and all techniques realized based on the above-described matters of the present invention are within the scope of the present invention.
Example 1
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 88 percent based on the molar quantity of N-phenyl acrylamide being 100 percent. The structural formula of the target product is as follows:
nuclear magnetic spectrum analysis was performed on the above white solid, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.90(br,1H),7.53(d,J=8.0Hz,2H),7.29-7.25(m,2H),7.06(t,J=7.2Hz,1H),6.22(br,1H),3.22(dd,J=13.2,6.8Hz,2H),2.76-2.59(m,4H),1.47-1.42(m,2H),1.28-1.24(m,6H),0.85(t,J=6.4Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.6,171.0,138.4,128.9,124.1,120.1,39.9,33.0,31.8,31.6,29.6,26.7,22.6,14.1。
example 2
To a 10mL reaction tube equipped with a magneton, N- (2-chlorophenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 83% based on the molar quantity of N- (2-chlorophenyl) acrylamide being 100%. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.35-8.20(m,2H),7.34(dd,J=7.9,0.8Hz,1H),7.21(t,J=7.5Hz,1H),7.06-6.96(m,1H),6.05(br,1H),3.24-3.19(m,2H),2.78(t,J=6.0Hz,2H),2.58(t,J=7.0Hz,2H),1.53-1.37(m,2H),1.30-1.16(m,6H),0.84(t,J=6.3Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ171.8,171.0,134.7,129.2,127.6,124.9,122.3,39.9,33.1,31.6,31.5,29.6,26.7,22.6,14.1。HRMS Calcd for C 16 H 23 ClN 2 O 2 [M+Na] + :m/z:333.1341,Found:333.1339。
example 3
To a 10mL reaction tube equipped with a magneton, N- (3-chlorophenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 86 percent based on the molar quantity of N- (3-chlorophenyl) acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ9.47(br,1H),7.67(s,1H),7.37(d,J=8.0Hz,1H),7.15(t,J=8.0Hz,1H),7.01(d,J=7.7Hz,1H),6.43(br,1H),3.22(dd,J=13.1,6.7Hz,2H),2.85-2.61(m,4H),1.51-1.38(m,2H),1.31-1.16(m,6H),0.84(t,J=6.7Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.6,171.2,139.7,134.5,129.9,124.0,120.1,117.9,40.0,32.9,31.6,31.6,29.6,26.7,22.6,14.1。HRMS Calcd for C 16 H 23 ClN 2 O 2 [M+Na] + :m/z:333.1341,Found:333.1343。
example 4
To a 10mL reaction tube equipped with a magneton, N- (3-bromophenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, is white solid, and has the yield of 56 percent based on the molar quantity of N- (3-bromophenyl) acrylamide of 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ9.38(br,1H),7.81(s,1H),7.43(d,J=8.0Hz,1H),7.18-7.08(m,2H),6.29(br,1H),3.23(dd,J=13.1,6.8Hz,2H),2.78-2.61(m,4H),1.48-1.45(m,2H),1.28-1.16(m,6H),0.86(t,J=6.0Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.6,171.1,139.9,130.2,127.0,122.9,122.6,118.4,40.1,32.9,31.7,31.6,29.6,26.7,22.7,14.1。HRMS Calcd for C 16 H 23 BrN 2 O 2 [M+Na] + :m/z:377.0835Found:377.0816。
example 5
To a 10mL reaction tube equipped with a magneton, N- (2-bromo-4-methylphenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 54 percent based on the molar quantity of N- (2-bromo-4-methylphenyl) acrylamide being 100 percent.
The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.03(t,J=8.2Hz,2H),7.34(s,1H),7.07(d,J=7.7Hz,1H),5.96(br,1H),3.22(dd,J=12.6,6.7Hz,2H),2.85-2.68(m,2H),2.63-2.54(m,2H),2.28(s,3H),1.53-1.40(m,2H),1.32-1.16(m,6H),0.85(t,J=6.6Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ171.8,170.7,135.6,133.2,132.7,128.9,122.6,114.1,39.9,33.1,31.7,31.6,29.7,26.7,22.6,20.6,14.1。HRMS Calcd for C 17 H 25 BrN 2 O 2 [M+Na] + :m/z:391.0992Found:391.0976。
example 6
To a 10mL reaction tube equipped with a magneton, N- (4-ethylphenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is a white solid, and the yield of the target product is 76 percent based on the molar quantity of N- (4-ethylphenyl) acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.79(br,1H),7.42(d,J=8.2Hz,2H),7.09(d,J=8.2Hz,2H),6.29(br,1H),3.21(dd,J=13.0,6.7Hz,2H),2.82-2.51(m,6H),1.52-1.41(m,2H),1.32-1.15(m,9H),0.85(t,J=6.0Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.5,170.8,140.2,136.0,128.3,120.2,39.9,33.0,32.0,31.6,29.6,28.4,26.7,22.6,15.8,14.1。HRMS Calcd for C 18 H 28 N 2 O 2 [M+Na] + :m/z:327.2043Found:327.2027。
example 7
To a 10ml reaction tube containing a magneton, N- (3, 5-dimethylphenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were successively introduced; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 83 percent based on the molar quantity of N- (3, 5-dimethylphenyl) acrylamide being 100 percent.
The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.69(br,1H),7.16(s,2H),6.71(s,1H),6.21(br,1H),3.22(dd,J=13.0,6.9Hz,2H),2.75-2.55(m,4H),2.24(s,6H),1.50-1.41(m,2H),1.29-1.19(m,6H),0.85(t,J=6.5Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.6,170.9,138.5,138.2,125.8,117.8,39.9,33.1,31.9,31.6,29.6,26.7,22.6,21.4,14.1。HRMS Calcd for C 18 H 28 N 2 O 2 [M+Na] + :m/z:327.2043Found:327.2026。
example 8
N- (o-tolyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added to a 10mL reaction tube equipped with a magneton; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product which is a white solid, wherein the yield of the target product is 60 percent based on the molar quantity of N- (o-tolyl) acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.22(br,1H),7.70(d,J=8.0Hz,1H),7.18-7.10(m,2H),7.08-7.01(m,1H),6.16(br,1H),3.21-3.16(m,2H),2.75-5.58(m,4H),2.23(s,3H),1.49-1.39(m,2H),1.32-1.20(m,6H),0.86(t,J=6.0Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.3,171.1,136.0,130.6,129.9,126.6,125.2,123.4,39.9,32.9,32.1,31.6,29.6,26.7,22.6,18.0,14.1。HRMS Calcd for C 17 H 26 N 2 O 2 [M+Na] + :m/z:313.1886Found:313.1881。
example 9
To a 10mL reaction tube equipped with a magneton, N- (3, 5-dimethoxyphenyl) acrylamide (0.2 mmol), 2- (hexylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 71 percent based on the molar quantity of N- (3, 5-dimethoxy phenyl) acrylamide being 100 percent.
The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ9.05(br,1H),6.79(d,J=4.0Hz,2H),6.34(br,1H),6.17(t,J=4.0Hz,1H),3.71(s,6H),3.20(dd,J=13.2,7.2Hz,2H),2.76-2.70(m,2H),2.63-2.57(m,2H),1.50-1.34(m,2H),1.30-1.14(m,6H),0.83(t,J=6.6Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.5,171.1,161.0,140.2,98.2,96.5,55.4,40.0,33.1,31.7,31.6,29.6,26.7,22.6,14.1。HRMS Calcd for C 18 H 28 N 2 O 4 [M+Na] + :m/z:359.1941Found:359.1926。
example 10
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- (butylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, is white solid, and the yield of the target product is 58 percent based on the molar quantity of N-phenyl acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ9.02(br,1H),7.53(d,J=7.9Hz,2H),7.26(t,J=7.2Hz,2H),7.06(t,J=7.4Hz,1H),6.36(br,1H),3.22(dd,J=13.1,6.8Hz,2H),2.8-2.6(m,4H),1.49-1.39(m,2H),1.32-1.26(m,2H),0.86(t,J=7.3Hz,3H)。 13 C NMR(100MHz,CDCl 3 )δ172.6,171.0,138.4,128.9,124.1,120.1,39.6,33.0,31.8,31.7,20.1,13.8。HRMS Calcd for C 14 H 20 N 2 O 2 [M+Na] + :m/z:271.1417Found:271.1420。
example 11
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- (t-butylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 83 percent based on the molar quantity of N-phenyl acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.97(br,1H),7.53-7.51(d,J=7.9Hz,2H),7.26(t,J=8.1Hz,2H),7.05(t,J=7.3Hz,1H),5.92(br,1H),2.68(t,J=5.9Hz,2H),2.52(t,J=7.1Hz,2H),1.31(s,9H)。 13 C NMR(100MHz,CDCl 3 )δ171.9,171.1,138.4,128.9,124.0,120.0,51.5,33.2,32.9,28.8。HRMS Calcd for C 14 H 20 N 2 O 2 [M+Na] + :m/z:271.1417Found:271.1425。
example 12
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- ((6-methoxy-6-oxohexyl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 62 percent based on the molar quantity of N-phenyl acrylamide being 100 percent. The structural formula of the target product is as follows:
the white solid was subjected to nuclear magnetic spectrum and mass spectrometry, and the data were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.84(br,1H),7.51(d,J=7.9Hz,2H),7.31-7.22(m,2H),7.06(t,J=7.3Hz,1H),6.30(br,1H),3.64(s,3H),3.22(dd,J=13.0,6.6Hz,2H),2.77-2.54(m,4H),2.25(t,J=7.4Hz,2H),1.62-1.43(m,4H),1.31-1.27(m,2H)。 13 C NMR(100MHz,CDCl 3 )δ174.2,172.6,170.9,138.4,129.0,124.2,120.0,51.6,39.6,33.9,33.1,31.9,29.2,26.4,24.5。HRMS Calcd for C 17 H 24 N 2 O 4 [M+Na] + :m/z:343.1628Found:343.1620。
example 13
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- ((8-methoxy-8-oxooctyl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 59 percent based on the molar quantity of N-phenyl acrylamide of 100 percent. The structural formula of the target product is as follows:
example 14
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- (benzylamino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 77 percent based on the molar quantity of N-phenyl acrylamide of 100 percent. The structural formula of the target product is as follows:
example 15
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2-oxo-2- ((2-phenylpropan-2-yl) amino) acetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 86 percent based on the molar quantity of N-phenyl acrylamide being 100 percent. The structural formula of the target product is as follows:
example 16
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- ((1- (benzyloxy) -1-oxo-3-phenylpropan-2-yl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is a white solid, and the yield of the target product is 67 percent based on the molar quantity of N-phenyl acrylamide being 100 percent.
The structural formula of the target product is as follows:
example 17
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- (((3 s,5s,7 s) -adamantan-1-yl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product which is a white solid, wherein the yield of the target product is 65 percent based on the molar quantity of N-phenyl acrylamide of 100 percent. This example is the post-modification of the antiviral drug amantadine. The structural formula of the target product is as follows:
example 18
To a 10mL reaction tube equipped with a magneton, N-phenylacrylamide (0.2 mmol), 2- ((3-methoxy-3-oxopropyl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product, wherein the target product is a white solid, and the yield of the target product is 72 percent based on the molar quantity of N-phenyl acrylamide of 100 percent. The structural formula of the target product is as follows:
example 19
To a 10mL reaction tube equipped with a magneton, N- (o-tolyl) acrylamide (0.2 mmol), 2- ((3-methoxy-3-oxopropyl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, adding saturated NaCl solution to quench the reaction, extracting the reaction with ethyl acetate for three times, combining the organic phases, drying the organic phases with anhydrous sodium sulfate, and separating the organic phases by column chromatography to obtain a target product which is a white solid, wherein the yield of the target product is 51 percent based on the molar quantity of N- (o-tolyl) acrylamide being 100 percent. The structural formula of the target product is as follows:
example 20
To a 10mL reaction tube equipped with a magneton, N- (3, 5-dimethylphenyl) acrylamide (0.2 mmol), 2- ((3-methoxy-3-oxopropyl) amino) -2-oxoacetic acid (0.4 mmol), lithium hydroxide monohydrate (0.4 mmol) and 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (0.01 mmol) were sequentially added; the reaction tube was evacuated, replaced with nitrogen three times, and then solvent anhydrous N, N-dimethylacetamide (2 mL) was added thereto, and the reaction tube was stirred at a reaction temperature of 35℃under irradiation of a blue LED lamp having a wavelength of 455nm for 12 hours. After the reaction, saturated NaCl solution is added to quench the reaction, the ethyl acetate is used for extraction for three times, the organic phases are combined and dried with anhydrous sodium sulfate, and the target product is obtained through column chromatography separation, and is white solid, and the yield of the target product is 54 percent based on the molar quantity of N- (3, 5-dimethylphenyl) acrylamide being 100 percent. The structural formula of the target product is as follows:
while the basic principles, principal features and advantages of the present invention have been described in the foregoing examples, it will be appreciated by those skilled in the art that the present invention is not limited by the foregoing examples, but is merely illustrative of the principles of the invention, and various changes and modifications can be made without departing from the scope of the invention, which is defined by the appended claims.
Claims (6)
1. A synthesis method of a visible light mediated butanediamide compound is characterized by comprising the following specific steps: placing an N-substituted acrylamide compound and an oxamide acid compound in a solvent, reacting under the action of a catalyst and alkali and under the condition of blue light irradiation and nitrogen environment, and separating after the reaction is finished to obtain a target product of the butanediamide compound; the catalyst is 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile, the alkali is lithium hydroxide monohydrate, the structure of the N-substituted acrylamide compound is shown in a formula A, the structure of the oxamide compound is shown in a formula B, and the structure of the butanediamide compound is shown in a formula C:
r in formula A and formula C 1 H, cl, br, C of a shape of H, cl, br, C 1-5 Alkyl or C 1-5 Alkoxy, R 1 The substitution being a unitary member on the benzene ringSubstituted or dibasic, R in formula B and formula C 2 Is C 1-5 Alkyl, adamantyl, phenyl C 1-5 Alkyl or ester-containing alkyl.
2. The method for synthesizing the visible light mediated butanediamide compound according to claim 1, wherein the method comprises the following steps: the molar ratio of the N-substituted acrylamide compound to the oxamide compound to the catalyst to the alkali is 1:1-3:0.01-0.1:1-3.
3. The method for synthesizing the visible light mediated butanediamide compound according to claim 1, wherein the method comprises the following steps: the solvent is anhydrous N, N-dimethylacetamide.
4. The method for synthesizing the visible light mediated butanediamide compound according to claim 1, wherein the method comprises the following steps: the blue light source is a blue LED lamp, the wavelength of the blue light source is 450-460 nm, and the power of the blue light source is 5-10W.
5. The method for synthesizing the visible light mediated butanediamide compound according to claim 1, wherein the method comprises the following steps: the reaction temperature in the reaction process is 25-40 ℃ and the reaction time is 6-24 h.
6. The method for synthesizing the visible light mediated butanediamide compound according to claim 1, characterized in that
In the following steps: after the reaction is finished, adding saturated NaCl solution into the reaction solution to quench the reaction, extracting with ethyl acetate for three times,
the organic phases are combined, dried by anhydrous sodium sulfate and separated by column chromatography to obtain the target compound succinamide compounds.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310145190.5A CN116162039A (en) | 2023-02-21 | 2023-02-21 | Synthesis method of visible light mediated butanediamide compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310145190.5A CN116162039A (en) | 2023-02-21 | 2023-02-21 | Synthesis method of visible light mediated butanediamide compound |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116162039A true CN116162039A (en) | 2023-05-26 |
Family
ID=86411079
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310145190.5A Pending CN116162039A (en) | 2023-02-21 | 2023-02-21 | Synthesis method of visible light mediated butanediamide compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116162039A (en) |
-
2023
- 2023-02-21 CN CN202310145190.5A patent/CN116162039A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2743261B1 (en) | Preparation method of crystal form i of the racemate of 4-hydroxy-2-oxo-1-pyrrolidine-acetamide | |
CA2894112A1 (en) | Novel antagonists of the glucagon receptor | |
KR20200086385A (en) | Cap-dependent endonuclease inhibitors | |
JPS5943459B2 (en) | N-alkylpiperidine derivative | |
HU177576B (en) | Process for preparing 2-amino-cyclohexane carboxylic acid,its amides and similar compounds | |
CN1216868C (en) | Pyridine-1-oxide derivative, and process for its transformation into pharmaceutically effective compunds | |
CN116751136A (en) | Novel preparation method of oxo-pyridine compound and key intermediate | |
ZA200601262B (en) | Cycloakylaminoacid compounds, processes for making and uses thereof | |
Hao et al. | Pd-catalysed β-selective C (sp 3)–H arylation of simple amides | |
CN109574906A (en) | A kind of preparation method of 3,3 '-two Indoleacetic esters | |
CN116162039A (en) | Synthesis method of visible light mediated butanediamide compound | |
JPH02306947A (en) | Preparation of chiral bata-amino acid | |
TW201912626A (en) | Method for preparing new toxin and intermediate thereof | |
KR20000064500A (en) | Optical separation method of 3- (para-chlorophenyl) -glutaramide | |
CA2717537A1 (en) | 2-trifluoromethylnicotinamide derivatives as hdl-cholesterol raising agents | |
CN114773176A (en) | Chlorpheniramine maleate impurity, and preparation method and application thereof | |
TWI628181B (en) | Intermediates of dpp-iv inhibitor and their preparation methods as well as the preparation method of dpp-iv inhibitor | |
CN113121417A (en) | Novel piperidine derivative and pharmaceutical application thereof | |
KR20000070057A (en) | Method for synthesis of rhizoferrin | |
JPS62155268A (en) | Synthesis of nizatidine | |
CN111892527B (en) | Indole derivatives and synthesis method thereof | |
Shemyakina et al. | Peculiarities of the tandem reaction between cyanoacetylenic alcohols and aminobenzoic acids: Synthesis of 5, 5-dialkyl-2-(3-aminophenyl)-4-oxo-4, 5-dihydrofuran-3-carbonitriles | |
CN109265391B (en) | Biphenyl polysubstituted 1,2,5, 6-tetrahydropyridine compound and synthetic method and application thereof | |
JPS59514B2 (en) | N-(1-adamantylmethyl)-piperazine | |
CN105111125B (en) | A kind of synthetic method of pharmaceutical intermediate condensed hetero ring ketone compounds |
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 |