CN104262236A - Method for preparing corresponding pyridine compound from 1,4-dihydropyridine compound - Google Patents
Method for preparing corresponding pyridine compound from 1,4-dihydropyridine compound Download PDFInfo
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- CN104262236A CN104262236A CN201410489164.5A CN201410489164A CN104262236A CN 104262236 A CN104262236 A CN 104262236A CN 201410489164 A CN201410489164 A CN 201410489164A CN 104262236 A CN104262236 A CN 104262236A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses a method for preparing a corresponding pyridine compound from a 1,4-dihydropyridine compound. The method comprises the following steps: adding a 1,4-dihydropyridine compound, tetra-n-butyl ammonium salt of eosin Y and potassium carbonate into an organic solvent-water mixed solvent, evenly mixing, and introducing air to react under the irradiation of visible light; and after the reaction finishes, adding ethyl acetate, washing respectively with water and saturated ammonium chloride, removing the inorganic alkali, regulating the system to a slightly acidic state, adding a small amount of activated carbon into the organic phase to remove the pigment, drying with anhydrous sodium sulfate, carrying out centrifugal drying, and recrystallizing to obtain the corresponding pyridine compound. Compared with the prior art, the method disclosed by the method uses oxygen in air, which is cheap, convenient and accessible, as the oxidizer. By using sunlight as the energy, the method is more beneficial to industrial production. By using the catalytic amount of non-metal photocatalyst, the method lowers the synthesis cost and prevents the noble metals from accumulation in drug synthesis.
Description
Technical field
The present invention relates to a kind of preparation method of pyridine compounds, the present invention relates to the method preparing corresponding pyridine compounds with Isosorbide-5-Nitrae-dihydropyridine compound exactly.
Background technology
1,4-dihydropyridine is that a class calcium channel blocker (Calcium Antagonists) is commonly called as " Horizon " class medicine, it is the very important compound of a class in hypertension therapeutic, mechanism of action is the calcium channel by blocking on cardiac muscle and vascular smooth muscle cell film, the outer flow of calcium ions of T suppression cell, makes intracellular calcium level reduce and cause tissue organ function's changes such as cardiovascular.Grind in 20th century sixties head, the seventies develops into a kind of newtype drug, and therapeutic domain comprises hypertension, cardiovascular disorder, cerebro-vascular diseases, peripheral vascular disease.Endocrinopathy etc.In organism, by cytopigment enzyme P-450 catalyzed oxidation, it is pathways metabolism main in NADH redox processes that Isosorbide-5-Nitrae-dihydropyridine aromatization is turned to corresponding pyridine derivate; In addition, this is also a kind of method that easy acquisition has anti-hypoxia, ischemia resisting active pyridine derivative, and therefore its raw material dihydropyridine is easier to preparation.This kind of dihydropyridine oxidation aromizing derivative also has the pharmaceutical activitys such as Cardiovarscular, cancer, AIDS.In addition, the dihydropyridine of oxidation d-mark, to corresponding pyridine derivate, can measure Isosorbide-5-Nitrae-dihydropyridine " Horizon " class medicine consumption in the body with going exploration and quantification as internal standard.Obtain corresponding pyridine compounds with this kind of Isosorbide-5-Nitrae-dihydropyridine compounds such as nifedipines and can be effectively applied to metabolic activities research and pharmacokinetics field and Drugs.
The method of synthesis polysubstituted pyridine compound the most frequently used in prior art is by based on Hantzsch reaction mechanism, by three components coupling one pot of cyclization Cheng Hansi ester Isosorbide-5-Nitrae-dihydropyridine, then obtains pyridine compounds through peroxidation aromizing.Traditional oxidation system uses high toxicity and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the iodic anhydride (I of Air–pollution From Combustion environment usually
2o
5) or Periodic acid (HIO
3), potassium periodate, molecular iodine, potassium permanganate or manganese oxide MnO
2, antimony pentachloride (SbCl
5), trichlorine oxygen tungsten (VOCl
3), the oxidation system such as sodium perborate.These methods compare poor efficiency generally speaking, and substantially all need heating.The oxygenant residue after the reaction of the equivalent used in addition not only causes constant to separation, also cause load to environment.Because the scheme treatment process reported is comparatively loaded down with trivial details, atom utilization is not high, and the pollutent of generation is large, no longer adapts to the economic model requirement based on less energy-consumption, low stain, low emission, therefore develop more efficient, the photosensitized oxidation aromatization method of more environmental protection in the urgent need to.
Summary of the invention
The present invention is a kind of method preparing corresponding pyridine compounds with Isosorbide-5-Nitrae-dihydropyridine overcoming prior art deficiency.
Technical conceive of the present invention is: the acidity utilizing the reactive hydrogen on dihydropyridine compound N, react with the additive basic salt of wormwood in system and generate exposed N negatively charged ion, reduce the oxidizing potential of dihydropyridine compound, make more efficiently to carry out photosensitized oxidation aromizing, obtain the pyridine compounds needed.Use 1 of the present invention, 4-dihydropyridine compound prepares corresponding pyridine compounds method: by 1, 4-dihydropyridine compound, the tetra-n-butyl ammonium salt of eosin W or W S, salt of wormwood joins in the mixed solvent of organic solvent and water and is uniformly mixed, described organic solvent is methyl alcohol, methylene dichloride, ethyl acetate, ether, acetone, toluene, normal hexane or sherwood oil, pass into air to react under radiation of visible light condition, after question response terminates, add ethyl acetate, use water respectively, saturated ammonium chloride washs, removing mineral alkali control agent pH value is 5.2 ~ 6.8, a small amount of activated carbon removing pigment is added in organic phase, again through anhydrous sodium sulfate drying, be spin-dried for, recrystallization obtains corresponding pyridine compounds and their, see formula 1.Isosorbide-5-Nitrae-dihydropyridine compound of the present invention refers to that, such as formula the compound shown in 2 to formula 16, the tetra-n-butyl ammonium salt of eosin W or W S used is see formula 17.
Use 1 of the present invention, it is by 1 that 4-dihydropyridine compound prepares the preferred method of corresponding pyridine compounds, the tetra-n-butyl ammonium salt of 4-dihydropyridine compound, eosin W or W S, salt of wormwood with amount of substance than 1:(0.01 ~ 0.03): the volume ratio that (0 ~ 4) joins organic solvent and water is 10:(0 ~ 1) in mixed solvent, organic solvent used is methyl alcohol or methylene dichloride, and pH value is 6.2.
Oxygenant described in the inventive method be adopt the Nature air in oxygen as unique oxygenant.Light source experimental room described in the inventive method is that the LED of 3 W 450 nm is irradiated, and the outdoor sunlight of the Nature that directly uses is as excited by visible light light source.Photosensitized oxidation reaction aromizing pyridine compounds described in the inventive method has outstanding in gentle productive rate, and can prepare on a large scale.Photosensitized oxidation temperature of reaction described in the inventive method is room temperature.
The inventive method has following advantage compared to synthetic technology before: using the oxygen in air as oxygenant, cheaply and be conveniently easy to get; The use of the non-metal optical catalyzer of catalytic amount, reduces synthesis cost, avoids precious metal accumulation in the product; Cheap salt of wormwood can meet the requirement of green synthetic chemistry as additive; The methanol-water mixed system selected is solvent, environmental protection, and the environmental pollution produced greatly reduces; In addition, the sunlight in the available external world replaces light source, makes industrial production advantageously; Further marketization application for this kind of medicine is also provided convenient by the pyridine derivate can producing important drugs utility value on a large scale.Secondly, the photosensitized oxidation operation that the inventive method provides is easy, uncovered room temperature is not afraid of air and moisture, only need the shorter time just can react, the higher product of purity just can be obtained through simple aftertreatment after reaction terminates, reaction terminates all right recycling further of rear solvent in addition, and plurality of advantages all embodies higher actual production meaning and the industrial application value of the inventive method, has possessed the possibility commercially producing pyridine compounds and their preferably.
Embodiment
Further describe the present invention below by specific embodiment, feature of the present invention will along with description explicitly clearly, but these examples of implementation are all exemplary, protection scope of the present invention is not limited to this.It should be appreciated by those skilled in the art, as long as do not departing under spirit of the present invention and example ranges, the amendment carry out ins and outs of the present invention and replacement are all falling within technical scope of the present invention.
Embodiment 1 shows the preparation of compound 1 such as formula 18
Get a reaction tube, 34.6 mg nifedipines (Nifedipine) 2 are added under uncovered, 6-dimethyl-4-O-Nitrophenylfluorone-1,4-dihydropyridine-3,5-bis-methyl carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, cross post with sherwood oil and acetone, obtain brown yellow oil liquid yield 73.3%.
1 H NMR:(400MHz, CDCl
3 ）δ = 7.74-7.70 (m, 1H), 7.54-7.51 (m, 1H), 7.47-7.43 (m, 1H), 6.56 (d, J=8.0Hz, 1H), 3.39 (s, 6H), 2.68 (s, 6H) ppm.
13 C NMR:(400 MHz, CDCl
3 )：δ =167.3, 161.5, 156.2, 135.1, 130.9, 130.5, 129.0, 128.8, 127.6, 65.6, 52.1, 29.7, 23.1, 19.2, 14.0 ppm. MS(70eV): m/z(%) : 344.1(008) [M
+], HRMS m/z (ESI) calcd for C
17 H
17 N
2 O
6 [M+H ]
+345.1079, found 345.1081。
Embodiment 2 shows the preparation of compound 2 such as formula 19
Get a reaction tube, 38.3 mg felodipine (Felodipine) 4-(2 are added under uncovered, 3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-ethyl-carbonate-5-methyl carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, post is crossed with sherwood oil and acetone, obtain pale yellowish oil liquid, productive rate 83.1%.
1 H NMR:(400MHz， CDCl
3) δ =7.48 (dd,
J = 6.8, 1.2Hz, 1H), 7.24-7.20 (t,
J = 8.0Hz, 1H), 7.07 (dd,
J = 6.0, 1.6Hz, 1H), 4.06-4.00 (m, 2H), 3.56 (s, 3H), 2.66 (d, J = 5.6Hz, 6H), 0.97-0.93 (t,
J = 7.2Hz, 3H) ppm.
13 C NMR:(400MHz, CDCl
3 ): δ =167.3, 166.7, 156.9, 156.7, 144.2, 137.7, 133.1, 131.5, 130.3, 128.3, 126.8, 126.2, 126.0, 61.4, 52.2, 23.5, 23.4, 13.5 ppm. MS(70eV) :m/z(%) :381.0(530) [M
+], HRMS m/z(ESI) calcd for C
18 H
18 Cl
2 O
4 (M+H)
+382.0603, found 382.0607。
Show the preparation of compound 3 such as formula 20 in embodiment 3
Get a reaction tube, 8 mg nimodipines (Nimodipine) 2 are added under uncovered, 6-dimethyl-4-m-nitro base-Isosorbide-5-Nitrae-dihydropyridine-3-propylene carbonate-5-carbonic acid-2 methoxy ethyl ester, the tetra-n-butyl ammonium salt TBA-eosinY of 0.2 mg organic photosensitive agent eosin W or W S, 1, the 8-diazabicylo 11 carbon-7-alkene of 15.7 μ L, 2 mL phenylfluoroforms, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless liquid, productive rate 78.4%.
1 H NMR:( 400MHz， CDCl
3 ）δ = 8.28-8.25 (m, 1H), 8.20-8.19(t,
J = 1.6Hz, 1H), 7.64-7.56 (m, 2H), 5.00-4.90 (m, 1H), 4.13 (s, 2H), 3.35 (s, 2H), 3.24 (s, 3H), 2.65(d,
J = 6.4Hz, 6H), 1.02(d,
J = 6.4Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl
3 ): δ=167.0, 166.5, 156.0, 155.9, 147.9, 137.9, 134.4, 129.2, 127.1, 123.5, 123.4, 69.8, 69.7, 64.4, 58.7, 22.9, 22.8, 21.3 ppm. MS(70eV) :m/z(%) : 416.1(584) [M
+], HRMS m/z(ESI) calcd for C
21 H
25 N
2 O
7 (M+H)
+417.1656, found 417.1661。
Embodiment 4 shows the preparation of compound 4 such as formula 21
Get a reaction tube, 25.3 mg 2 are added under uncovered, 6-dimethyl-Isosorbide-5-Nitrae-dihydropyridine-3,5-Ue-5908, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless oil liquid, productive rate 80.2%.
1 H NMR:(400 MHz， CDCl
3 ) δ = 8.70 (s, 1H), 4.43-4.37 (q,
J = 7.2Hz, 4H), 2.87 (s, 6H), 1.44-1.40 (t,
J = 7.2Hz, 6H) ppm.
13 C NMR:(400 MHz, CDCl
3) δ =165.6, 162.0, 123.4, 61.6, 24.5, 14.3 ppm. MS(70 eV) :m/z (%) : 251.1(158) [M
+], HRMS m/z(ESI) calcd for C
13 H
18 NO
4 (M+H)
+252.1230, found 252.1232。
Embodiment 5 shows the preparation of compound 5 such as formula 22
Get a reaction tube, 26.7 mg2 are added, 6-dimethyl-4-sec.-propyl-Isosorbide-5-Nitrae-dihydropyridine-3 under uncovered, 5-bis-methyl carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, post is crossed with sherwood oil and acetone, obtain corresponding pyridine compounds, as colourless oil liquid, productive rate 82.8%.
1 H NMR:(400MHz， CDCl
3 ) δ = 8.72 (s, 1H), 3.94 (s, 6H), 3.10-3.03 (m,1H), 2.87 (s, 6H), 1.27 (s, 3H), 1.25 (s, 3H) ppm;
13 C NMR: (400MHz, CDCl
3 ): δ = 165.7, 162.3, 123.2, 52.5, 33.4, 29.3, 24.2, 22.6, 21.6 ppm. MS(70eV) :m/z(%) : 265.1(314) [M+], HRMS m/z(ESI) calcd for C
14 H
20 NO
4 (M+H)
+ 266.1392, found m/z(ESI): 266.1393.。
Embodiment 6 shows the preparation of compound 6 such as formula 23
Get a reaction tube, 2 of 32.9 mg are added under uncovered, 6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-bis-ethyl-carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post obtain sterling, productive rate 92.1% with sherwood oil and acetone.
1 H NMR:(400MHz， CDCl
3 ) δ = 7.37-7.36(m, 3H), 7.26-7.24 (m, 2H), 4.03-3.98 (q,
J = 7.2Hz, 4H), 2.61(s, 6H), 0.92-0.88 (t,
J = 7.2Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl3): δ = 167.7, 155.3, 146.2, 136.5, 128.4, 128.0, 127.8, 126.9, 61.3, 58.2, 22.7, 18.3, 13.4 ppm. MS(70eV) :m/z(%) :327.1(471) [M
+], HRMS m/z(ESI)calcd for C
19 H
22 NO
4 (M+H)
+328.1539, found 328.1543。
Embodiment 7 shows the preparation of compound 7 such as formula 24
Get a reaction tube, 2 of 36.3 mg are added under uncovered, 6-dimethyl-4-rubigan-Isosorbide-5-Nitrae-dihydropyridine-3,5-bis-ethyl-carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain pale yellowish oil liquid, productive rate 85.1%.
1 H NMR:（400MHz, CDCl
3 ）δ = 7.35 (d,
J = 8.4Hz, 2H), 7.21-7.19 (m, 2H), 4.06-4.01 (q,
J = 7.2Hz, 4H), 2.60 (s, 6H), 0.99-0.96 (t,
J =7.2Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl
3 ): δ = 167.4, 155.5, 145.0, 134.8, 134.7, 129.5, 129.4, 128.4, 128.3, 126.9, 61.5, 22.7, 13.6 ppm. MS(70eV):m/z(%): 3611(081) [M
+], HRMS m/z(ESI)calcd for C
19 H
21 ClNO
4 (M+H)
+362.1151, found 362.1154.。
Embodiment 8 shows the preparation of compound 8 such as formula 25
Get a reaction tube, the mg2 of 34.7 is added under uncovered, 6-dimethyl-4-is to fluorophenyl-Isosorbide-5-Nitrae-dihydropyridine-3,5-bis-ethyl-carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless oil liquid, productive rate 79.8%.
1 H NMR:(400MHz， CDCl
3 ) δ =7.59-7.55 (m, 2H), 7.14-7.10 (m, 2H), 4.49-4.43 (q,
J = 7.2Hz, 2H), 4.17-4.12 (q,
J = 7.2Hz, 2H), 2.61 (s, 3H), 2.36 (s, 3H), 1.44-1.41(t,
J = 7.2Hz, 3H), 1.08-1.04 (t,
J = 7.2Hz, 3H) ppm.
13 C NMR: (400MHz, CDCl
3 ): δ=168.3, 168.2, 164.5, 162.1, 155.3, 155.2, 143.0, 135.7, 130.3, 130.2, 130.0, 128.6, 127.3, 115.5, 115.2, 61.7, 61.6, 23.0, 16.9, 14.2, 13.7. MS(70eV) :m/z(%) :345.1(367) [M+], HRMS m/z(ESI)calcd for C
19 H
21 FNO
4 (M)+346.1443, found 346.1449.。
Embodiment 9 shows the preparation of compound 9 such as formula 26
Get a reaction tube, 2 of 39.7mg are added under uncovered, the salt of wormwood of tetra-n-butyl ammonium salt TBA-eosinY, 27.6mg of 6-dimethyl-4-p-trifluoromethyl phenyl-Isosorbide-5-Nitrae-dihydropyridine-3,5-bis-ethyl-carbonate, 1.13mg organic photosensitive agent eosin W or W S, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless oil liquid, productive rate 84.6%.
1 H NMR:(400MHz， CDCl
3 ) δ=7.64 (d,
J = 8.0 Hz, 2H), 7.39 (d,
J = 8.0Hz, 2H), 4.04-3.98 (q,
J = 7.2Hz, 4H), 2.62 (s, 6H), (t,
J = 7.2Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl
3 ): δ =167.3, 155.9, 144.7, 140.3, 131.2, 130.9, 130.6, 128.7, 127.9, 126.5, 125.2, 125.0, 125.0, 124.9, 122.5, 61.5, 23.0, 13.5 ppm; MS(70eV) :m/z(%) :395.1(344) [M+], HRMS m/z(ESI)calcd for C
20 H
21 F
3 NO
4 (M+H)
+396.1410, found 396.1417.。
Embodiment 10 shows the preparation of compound 10 such as formula 27
Get a reaction tube, the 4-of 35.4mg is added to cyano-phenyl-2 under uncovered, the salt of wormwood of tetra-n-butyl ammonium salt TBA-eosinY, 27.6mg of 6-dimethyl-Isosorbide-5-Nitrae-dihydropyridine-3,5-bis-ethyl-carbonate, 1.13mg organic photosensitive agent eosin W or W S, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless oil liquid, productive rate 89.3%.
1 H NMR:(400MHz, CDCl
3 ) δ = 7.70 (d,
J = 8.4 Hz, 2H), 7.39 (d,
J = 8.4 Hz, 2H), 4.07-4.01(q,
J =7.2Hz, 4H), 2.70 (s, 6H), 0.98-0.95 (t,
J = 7.2Hz, 6H) ppm.
13 C NMR: (400MHz, CDCl
3 ): δ =166.6, 155.8, 131.8, 129.1, 118.1, 112.8, 61.8, 22.4, 13.6 ppm. MS(70 eV): m/z(%): 352.1(423) [M
+], HRMS m/z(ESI)calcd for C
20 H
21 N
2 O
4 (M+H)
+353.1496, found 353.1496.。
Embodiment 11 shows the preparation of compound 11 such as formula 28
Get a reaction tube, 2 of 35.9 mg are added under uncovered, 6-dimethyl-4-p-methoxyphenyl-Isosorbide-5-Nitrae-dihydropyridine-3,5-bis-ethyl-carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature react 12 hours, vacuum is spin-dried for, and crosses post with sherwood oil and acetone, obtain colourless oil liquid sterling, productive rate 90.1%.
1 H NMR: (400MHz， CDCl
3 ) δ = 7.18 (d,
J = 8.8Hz, 2H), 6.88 (d,
J = 8.4Hz, 2H), 4.07-4.01(q,
J = 7.2Hz, 4H), 3.81 (s, 3H), 2.58 (s, 6H), 0.99-0.96 (t,
J = 7.2Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl
3): δ=167.7, 159.9, 154.9, 146.3, 129.4, 129.2, 128.4, 127.5, 113.6, 61.4, 55.2, 31.8, 29.6, 29.3, 22.6, 22.4, 14.0, 13.6 ppm. MS (70eV): m/z(%) :357.1(576)[M
+], HRMS m/z(ESI) calcd for C
20 H
24 NO
5 (M)
+358.1644, found 358.1649。
Embodiment 12 shows the preparation of compound 12 such as formula 29
Get a reaction tube, 2,6-dimethyl-3, the 4-Dimethoxyphenyls-1 of 38.9 mg are added under uncovered, 4-dihydropyridine-3,5-bis-ethyl-carbonate, the tetra-n-butyl ammonium salt TBA-eosinY of 1.13 mg organic photosensitive agent eosin W or W Ss, the salt of wormwood of 27.6 mg, the mixed solvent (second alcohol and water presses the volume ratio composition of 10:1) of 5.5 mL water and ethanol, at room temperature reacts 12 hours, vacuum is spin-dried for, cross post with sherwood oil and acetone, obtain white solid, productive rate 92.3%.
1 H NMR: (400MHz， CDCl
3 ) δ = 7.03-7.00 (t,
J = 8.0Hz, 1H), 6.92 (d,
J = 8.4Hz, 1H), 6.69 (d,
J = 7.6Hz, 1H), 4.10-3.98 (m, 4H), 3.87 (d,
J = 7.6Hz, 3H), 3.64 (s, 3H), 2.64 (s, 6H), 0.97-0.93 (t,
J = 7.2Hz, 6H) ppm.
13 C NMR:(400MHz, CDCl
3 ): δ =167.3, 155.8, 152.4, 146.2, 130.9, 127.2, 123.4, 121.7, 113.0, 61.2, 60.5, 55.9, 23.1, 13.5 ppm.MS (70eV) :m/z(%) : 387.1 (682) [M
+], HRMS m/z (ESI) calcd for C
21 H
26 NO
6 [M+Na]
+410.1567, found 410.1574.。
Claims (2)
1. with 1, 4-dihydropyridine compound prepares corresponding pyridine compounds method, it is characterized in that 1, 4-dihydropyridine compound, the tetra-n-butyl ammonium salt of eosin W or W S, salt of wormwood joins in the mixed solvent of organic solvent and water and is uniformly mixed, described organic solvent is methyl alcohol, methylene dichloride, ethyl acetate, ether, acetone, toluene, normal hexane or sherwood oil, pass into air to react under radiation of visible light condition, after question response terminates, add ethyl acetate, use water respectively, saturated ammonium chloride washs, removing mineral alkali regulation system pH value is 5.2 ~ 6.8, a small amount of activated carbon removing pigment is added in organic phase, again through anhydrous sodium sulfate drying, be spin-dried for, recrystallization obtains corresponding pyridine compounds and their.
2. with 1,4-dihydropyridine compound prepares corresponding pyridine compounds method, it is characterized in that 1, the tetra-n-butyl ammonium salt of 4-dihydropyridine compound, eosin W or W S, salt of wormwood with amount of substance than 1:(0.01 ~ 0.03): the volume ratio that (0 ~ 4) joins organic solvent and water is 10:(0 ~ 1) in mixed solvent, organic solvent used is methyl alcohol or methylene dichloride, and regulation system pH value is 6.2.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018196681A1 (en) * | 2017-04-26 | 2018-11-01 | 中国科学院上海药物研究所 | Eutectic of nifedipine with isonicotinamide |
| CN109020875A (en) * | 2018-08-27 | 2018-12-18 | 北京市药品检验所 | Dihydropyridine compounds dehydroaromatizationof method and the purposes in drug detection |
| CN110511180A (en) * | 2019-06-12 | 2019-11-29 | 北京鑫开元医药科技有限公司 | A kind of Preparation method and use of pyridine derivate |
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| JPH0429972A (en) * | 1990-05-23 | 1992-01-31 | Tokawa Tetsuo | New production of 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine compound |
| CN103242221A (en) * | 2012-02-08 | 2013-08-14 | 上海医药工业研究院 | Preparation method of dihydropyridine compound |
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| JPH0429972A (en) * | 1990-05-23 | 1992-01-31 | Tokawa Tetsuo | New production of 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine compound |
| CN103242221A (en) * | 2012-02-08 | 2013-08-14 | 上海医药工业研究院 | Preparation method of dihydropyridine compound |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018196681A1 (en) * | 2017-04-26 | 2018-11-01 | 中国科学院上海药物研究所 | Eutectic of nifedipine with isonicotinamide |
| CN109020875A (en) * | 2018-08-27 | 2018-12-18 | 北京市药品检验所 | Dihydropyridine compounds dehydroaromatizationof method and the purposes in drug detection |
| CN110511180A (en) * | 2019-06-12 | 2019-11-29 | 北京鑫开元医药科技有限公司 | A kind of Preparation method and use of pyridine derivate |
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