CN108727385A - A kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives - Google Patents
A kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives Download PDFInfo
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- pyrimidin
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- 150000002576 ketones Chemical class 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- -1 after reaction Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229940011182 cobalt acetate Drugs 0.000 claims abstract description 6
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 claims abstract description 6
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims abstract description 6
- 229940071536 silver acetate Drugs 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims abstract description 5
- 238000006467 substitution reaction Methods 0.000 claims abstract description 5
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical class CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- CZCXETFSJAOEHW-UHFFFAOYSA-N C(=O)N.CON1C=CC2=CC=CC=C12 Chemical class C(=O)N.CON1C=CC2=CC=CC=C12 CZCXETFSJAOEHW-UHFFFAOYSA-N 0.000 claims abstract description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 4
- 239000001632 sodium acetate Substances 0.000 claims abstract description 4
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 4
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 3
- 229960004249 sodium acetate Drugs 0.000 claims abstract description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical group FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- GTVWPXDPNQJYNV-UHFFFAOYSA-N 1-methoxyindole Chemical class C1=CC=C2N(OC)C=CC2=C1 GTVWPXDPNQJYNV-UHFFFAOYSA-N 0.000 claims description 2
- 238000001311 chemical methods and process Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- ZBCKWHYWPLHBOK-UHFFFAOYSA-N cyclohexylphosphane Chemical compound PC1CCCCC1 ZBCKWHYWPLHBOK-UHFFFAOYSA-N 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 6
- 238000010189 synthetic method Methods 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000000706 filtrate Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- VNYMSZNLHWOCCO-UHFFFAOYSA-N pyrrolo[2,3-f]quinazolin-2-one Chemical class C1=NC=C2C3=NC(=O)C=C3C=CC2=N1 VNYMSZNLHWOCCO-UHFFFAOYSA-N 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 0 *NC([n](ccc1c2)c1ccc2Br)=O Chemical compound *NC([n](ccc1c2)c1ccc2Br)=O 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- FEKWWZCCJDUWLY-UHFFFAOYSA-N 3-methyl-1h-pyrrole Chemical class CC=1C=CNC=1 FEKWWZCCJDUWLY-UHFFFAOYSA-N 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N CCc1ccccc1 Chemical compound CCc1ccccc1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- XBDFAJJYUPWKBO-UHFFFAOYSA-N CON(CC(c1cc(cccc2)c2[n]11)c2ccccc2)C1=O Chemical compound CON(CC(c1cc(cccc2)c2[n]11)c2ccccc2)C1=O XBDFAJJYUPWKBO-UHFFFAOYSA-N 0.000 description 1
- LRNRHOUGAQXFPO-UHFFFAOYSA-N CONC([n]1c2ccccc2cc1)=O Chemical compound CONC([n]1c2ccccc2cc1)=O LRNRHOUGAQXFPO-UHFFFAOYSA-N 0.000 description 1
- FKHMAYHUPHLYPX-UHFFFAOYSA-N COc(cc1)cc(cc2C(CN3O)c4ccccc4)c1[n]2C3=O Chemical compound COc(cc1)cc(cc2C(CN3O)c4ccccc4)c1[n]2C3=O FKHMAYHUPHLYPX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a kind of preparation methods for the novel polysubstituted dihydro-pyrimidin diindyl ketone derivatives for belonging to technical field of organic synthesis.The method is：Into reactor, substitution N- methoxy-Indole formamides are added, substituted phenylethylene, cobalt acetate, silver acetate, sodium acetate, 4- picolines and tricyclohexyl phosphine, are stirred in a solvent, after reaction, crude product is obtained using Rotary Evaporators concentration filtrate, crude product purified by silica gel column chromatography for separation obtains target compound.The synthetic method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives provided by the invention has the features such as scientific and reasonable, synthetic method is simple, and target compound yield is higher, and product is easy to purifying.Its reaction equation is as follows：
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation side of dihydro-pyrimidin diindyl ketone derivatives
Method.
Background technology
Nitrogen heterocyclic ring is universally present in natural products and in the molecule with biology and medicinal activity.In these heterocycles
In compound, pyrimidone and indoles are the important parent nucleus of two classes.Pyrimidinones all have in many fields answers well
With foreground, for example, anticancer and antibacterial activity.(J.Med.Chem.1987,30,1256-1261.) Benzazole compounds are in drug
Indispensable role is also played in design and the synthesis of natural products.For example, using indoles as the compound of parent nucleus respectively by
For hypertension therapeutic and antibacterials.((a)Hypertension.1997,29, 651-658.(b)
J.Antimicrob.Chemother.2004,54,549-552.)
As the two kinds of nitrogenous heterocyclic combinations of pyrimidone and indoles, dihydro-pyrimidin diindyl ketone derivatives are likely to have this
The advantage of two kinds of compounds.In view of the extensive bioactivity and application value of dihydro-pyrimidin diindyl ketone derivatives, development one
The new method of synthesizing dihydro pyrimido indolone derivatives is of great significance with planting practicability and effectiveness.
The method for preparing dihydro-pyrimidin diindyl ketone derivatives has：
1) 2014, Sunliang Cui seminars reported with N- pivaloyls oxygroup indole carboxamides substance and alkynes
Or alkene synthesizes pyrimido indolone derivatives under rhodium catalysis.(J.Org.Chem.2014,79,6490-6500.)
2) 2016, Zhi-Zhen Huang seminars reported with N- methoxy-Indoles carboxamide and alpha-chloro
Acetophenone synthesizing dihydro pyrimido indolone derivatives under rhodium catalysis.(Eur.J.Org.Chem.2016,5399–5404.)
Prepare the distinct disadvantage in the above method of dihydro-pyrimidin diindyl ketone derivatives：With Noble Metal Rhodium.
Invention content
In order to overcome the above-mentioned deficiencies of the prior art, as to existing dihydro-pyrimidin diindyl ketone derivatives synthetic method
Supplement, the present invention provides a kind of preparation methods of the polysubstituted dihydro-pyrimidin diindyl ketone derivatives of cheap metal cobalt catalysis.
A kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives, the dihydro-pyrimidin diindyl ketone derivatives
With structure shown in Formulas I：
R1Substituent group is selected from fluorine, chlorine, bromine, methoxyl group, methyl；R2Selected from methoxyl group, fluorine, chlorine, bromine；It is characterized in that, to
In reactor, substitution N- methoxy-Indole formamides, substituted phenylethylene, cobalt acetate, silver acetate, sodium acetate, 4- methyl pyrroles is added
Pyridine and tricyclohexyl phosphine.After being stirred to react in a solvent, it is concentrated to give crude product using Rotary Evaporators, crude product uses
The isolated target product of silica gel column chromatography, chemical process are shown in reaction equation II：
The substitution N- methoxy-Indoles formamide, substituted phenylethylene, cobalt acetate, tricyclohexyl phosphine, silver acetate, acetic acid
The molar ratio of sodium and 4- picolines is 1：2：0.1：0.2： 2：2：4.The solvent is hexafluoroisopropanol, and reaction temperature is
120 DEG C, the reaction time is 3 h.
Beneficial effects of the present invention are：The synthetic method science of dihydro-pyrimidin diindyl ketone derivatives provided by the invention is closed
Reason provides a kind of new way of the polysubstituted dihydro-pyrimidin diindyl ketone of synthesis, has obtained having a variety of substitutions by this method
The dihydro-pyrimidin diindyl ketone derivatives of base, feature are：Synthetic method is simple, and target compound yield is higher, and product is easy to
Purifying.
Description of the drawings
Fig. 1 is the NMR spectra of compound 3aa prepared by embodiment 1；
Fig. 2 is the NMR spectra of compound 3ca prepared by embodiment 3；
Fig. 3 is the NMR spectra of compound 3ab prepared by embodiment 7.
Specific implementation mode
The present invention is described in more detail with specific embodiment below in conjunction with the accompanying drawings：
Test method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as
Without specified otherwise, commercially obtain.
Embodiment 1
1) preparation of dihydro-pyrimidin diindyl ketone derivatives 3aa
N- methoxy-Indole formamide 1a (0.2mmol, 38.0mg), 2a are added into 15ml heavy wall pressure pipes
(0.4mmol, 41.7mg) and cobalt acetate (0.02mmol, 5.0mg), silver acetate (0.4mmol, 66.8mg), sodium acetate
Hexafluoroisopropanol (2mL) is added in (0.4mmol, 54.4mg) and tricyclohexyl phosphine (0.04mmol, 11.2mg), in 120 DEG C of oil
It stirs, reacts 3 hours in bath.After completion of the reaction, it removes solvent using Rotary Evaporators and obtains crude product, crude by column chromatography
It detaches (200-300 mesh silica gel) (petrol ether/ethyl acetate=8/1), removes solvent using Rotary Evaporators, obtain target product
Unsubstituted dihydro-pyrimidin diindyl ketone 3aa, yield 95%.
Spectrum elucidation data 3aa:
1H NMR(500MHz,CDCl3) δ 8.45 (d, J=8.3Hz, 1H), 7.46-7.29 (m, 7H), 7.22 (t, J=
7.5Hz, 1H), 6.07 (s, 1H), 4.57 (dd, J=9.8,5.4Hz, 1H), 3.98-3.85 (m, 2H), 3.85 (s, 3H)13C
NMR(125MHz,CDCl3)δ 152.5,138.3,137.2,135.5,129.5,128.2,128.0,124.3,123.1,
120.2, 115.5,105.2,62.7,54.6,40.9.HRMS(ESI)m/z calcd for C18H16N2NaO2 +[M+Na]+
315.1104,found 315.1113.
Embodiment 2
The 1a in example 1 is replaced with 1b, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ba:
1H NMR(500MHz,CDCl3) δ 8.39 (dd, J=9.0,4.7Hz, 1H), 7.40 (dt, J=11.6,6.7Hz,
3H), 7.33 (d, J=6.8Hz, 2H), 7.08 (dd, J=8.8,2.3 Hz, 1H), 7.04 (td, J=9.2,2.4Hz, 1H),
6.03 (s, 1H), 4.57 (dd, J=9.6,5.5Hz, 1H), 3.98-3.87 (m, 2H), 3.85 (s, 3H)13C NMR
(125MHz, CDCl3)δ160.4,158.5,152.3,138.9,138.0,131.8,130.4,130.4,129.0,
1228.2,116.4,116.4,112.1,111.9,105.9,105.7,104.9,62.8,54.6,40.9.
Embodiment 3
The 1a in example 1 is replaced with 1c, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ca:
1H NMR(500MHz,CDCl3) δ 8.36 (d, J=8.8Hz, 1H), 7.46-7.33 (m, 5H), 7.34-7.30 (m,
3H), 7.29-7.23 (m, 2H), 6.00 (s, 5H), 4.56 (dd, J=9.1,5.6Hz, 1H), 3.98-3.85 (m, 2H), 3.85
(s,3H).13C NMR(125 MHz,CDCl3)δ152.1,138.7,137.9,133.8,130.7,129.0,128.7,128.2,
124.4,119.8,116.4,104.4,62.8,54.5,40.9.
Embodiment 4
The 1a in example 1 is replaced with 1d, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3da:
1H NMR(500MHz,CDCl3) δ 8.31 (d, J=8.8Hz, 1H), 7.55 (s, 1H), 7.43-7.35 (m, 4H),
7.31 (d, J=6.9Hz, 2H), 6.00 (s, 1H), 4.56 (dd, J=9.8,5.6Hz, 1H), 3.97-3.86 (m, 2H), 3.84
(s,3H).13C NMR(125MHz, CDCl3)δ156.2,152.5,138.4,137.9,130.4,130.1,128.9,128.2,
128.0, 116.1 112.7,105.0,103.1,62.7,55.6,54.8,40.9.
Embodiment 5
The 1a in example 1 is replaced with 1e, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ea:
1H NMR(500MHz,CDCl3) δ 8.32 (d, J=9.0Hz, 1H), 7.42-7.30 (m, 5H), 6.93 (dd, J=
9.0,2.4Hz, 1H), 6.90 (d, J=2.2Hz, 1H), 5.99 (s, 1H), 4.55 (dd, J=9.8,5.4Hz, 1H), 3.95-
3.85(m,2H),3.84(s,3H), 3.82(s,3H).13C NMR(125MHz,CDCl3)δ156.2,152.5,138.4,
137.9, 130.4,130.1,128.9,128.2,128.02,116.2,112.7,105.0,103.1,62.8,55.6,
54.8,40.9.
Embodiment 6
The 1a in example 1 is replaced with 1f, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3fa:
1H NMR(500MHz,CDCl3) δ 8.30 (d, J=8.4Hz, 1H), 7.38 (m, 3H), 7.34-7.30 (m, 2H),
7.22 (s, 1H), 7.14 (d, J=8.4Hz, 1H), 5.99 (s, 1H), 4.55 (dd, J=9.2,5.5Hz, 1H), 3.96-3.84
(m,2H),3.84(s,3H), 2.42(s,3H).13C NMR(125MHz,CDCl3)δ152.6,138.5,137.2,133.6,
132.6,129.7,128.9,128.2,128.0,125.6,120.2,115.1,104.9,62.7,54.7, 40.9,21.4.
Embodiment 7
The 2a in example 1 is replaced with 2b, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ab:
1H NMR(500MHz,CDCl3) δ 8.44 (d, J=8.3Hz, 1H), 7.43 (d, J=7.7Hz, 1H), 7.31 (t, J
=7.8Hz, 1H), 7.26-7.18 (m, 3H), 6.92 (d, J=8.6 Hz, 2H), 6.05 (s, 1H), 4.52 (dd, J=10.1,
5.5Hz,1H),3.91–3.83(m, 5H),3.83(s,3H).13C NMR(125MHz,CDCl3)δ159.3,152.5,137.7,
135.5,130.2,129.5,124.2,123.1,120.2,115.5,114.3,105.0,62.7,55.3, 54.8,
40.2.HRMS(ESI)m/z calcd for C19H19N2O3 +[M+H]+323.1390, found 323.1398.
Embodiment 8
The 2a in example 1 is replaced with 2c, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ac:
1H NMR(500MHz,CDCl3) δ 8.44 (d, J=8.3Hz, 1H), 7.44 (d, J=7.7Hz, 1H), 7.36-
7.28 (m, 3H), 7.23 (t, J=7.5Hz, 1H), 7.09 (t, J=8.6 Hz, 2H), 6.06 (s, 1H), 4.57 (dd, J=
9.4,4.9Hz, 1H), 3.92 (dd, J=10.8,5.4Hz, 1H), 3.85 (s, 3H), 3.82 (d, J=10.5Hz, 1H)13C
NMR(125MHz, CDCl3)δ163.3,161.4,152.4,137.0,135.5,134.1,129.8,129.4,124.4,
123.2,120.3,116.0,115.8,115.5,105.2,62.8,54.7,40.2.HRMS(ESI) m/z calcd for
C18H16FN2O2 +[M+H]+311.1190,found 311.1197.
Embodiment 9
The 2a in example 1 is replaced with 2d, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ad:
1H NMR(500MHz,CDCl3) δ 8.44 (d, J=8.3Hz, 1H), 7.44 (d, J=7.7Hz, 1H), 7.39-
7.30 (m, 3H), 7.25 (m, 3H), 6.06 (s, 1H), 4.55 (dd, J=9.5,5.3Hz, 1H), 3.92 (dd, J=10.8,
5.3Hz, 1H), 3.85 (s, 3H), 3.81 (d, J=10.4Hz, 1H)13C NMR(125MHz,CDCl3)δ152.4,136.9,
136.6, 135.5,133.9,129.6,129.4,129.1,124.4,123.3,120.3,115.5,105.3,62.8,
54.5,40.3.HRMS(ESI)m/z calcd for C18H16ClN2O2 +[M+H]+327.0895, found 327.0903.
Embodiment 10
The 2a in example 1 is replaced with 2e, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ae:
1H NMR(500MHz,CDCl3) δ 8.43 (d, J=8.2Hz, 1H), 7.52 (d, J=8.2Hz, 2H), 7.44 (d, J
=7.7Hz, 1H), 7.33 (t, J=7.7Hz, 1H), 7.22 (m, 3H), 6.06 (s, 1H), 4.54 (dd, J=9.3,5.3Hz,
1H), (d, J=10.3Hz, 1H) of 3.92 (dd, J=10.7,5.3 Hz, 1H), 3.84 (s, 3H), 3.8113C NMR(125MHz,
CDCl3)δ152.4,137.4,136.5,135.5,132.1,129.9,129.4,124.4,123.3, 122.0,120.3,
115.5,105.3,62.8,54.5,40.3.HRMS(ESI)m/z calcd for C18H16BrN2O2 +[M+H]+371.0390,
found 371.0394.
Table 1
Claims (3)
1. a kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives, the dihydro-pyrimidin diindyl ketone derivatives tool
There is structure shown in Formulas I：
In Formulas I, in order to make the purpose , technical scheme and advantage of the present invention be clearer, the following specific example of the present invention
It illustrates.It is clear that the invention is not restricted to which above embodiment, can also be suitable for all kinds of substrates there are many deformation.This field
The those of ordinary skill's all deformations that directly can export or associate from the disclosure of invention, be considered as the present invention's
Protection domain.R1Substituent group is selected from fluorine, chlorine, bromine, methoxyl group, methyl；R2Substituent group is selected from methoxyl group, fluorine, chlorine, bromine；It is special
Sign is, into reactor, is added and replaces N- methoxy-Indole formamides, substituted phenylethylene, cobalt acetate, silver acetate, sodium acetate,
4- picolines and tricyclohexyl phosphine.It stirs in a solvent, after completion of the reaction, crude product is concentrated to give using Rotary Evaporators,
Crude product uses the isolated target product of silica gel column chromatography, chemical process to see reaction equation II：
2. preparation method according to claim 1, substitution N- methoxy-Indoles formamide, substituted phenylethylene, cobalt acetate, three
Cyclohexyl phosphine, silver acetate, sodium acetate and 4- picolines molar ratio be 1：2：0.1：0.2：2：2：4.
3. preparation method described in accordance with the claim 1, it is characterised in that：Solvent is hexafluoroisopropanol, reaction temperature 120
DEG C, the reaction time is 3 hours.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232585A (en) * | 2018-11-29 | 2019-01-18 | 青岛科技大学 | A kind of preparation method of polysubstituted pyrimidine and two indolone derivatives |
| CN110526852A (en) * | 2019-09-18 | 2019-12-03 | 湖北斯柏生物科技有限公司 | A kind of preparation method of indoles |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103755708A (en) * | 2013-12-31 | 2014-04-30 | 浙江大学 | Preparation method of indole or pyrrolopyrimidine derivative |
| CN105481865A (en) * | 2015-12-21 | 2016-04-13 | 广东工业大学 | Preparation method of pyrimidine [1,6-a] indole heterocyclic derivative |
-
2018
- 2018-07-14 CN CN201810772736.9A patent/CN108727385B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103755708A (en) * | 2013-12-31 | 2014-04-30 | 浙江大学 | Preparation method of indole or pyrrolopyrimidine derivative |
| CN105481865A (en) * | 2015-12-21 | 2016-04-13 | 广东工业大学 | Preparation method of pyrimidine [1,6-a] indole heterocyclic derivative |
Non-Patent Citations (2)
| Title |
|---|
| YAN ZHANG 等: "Rh(III)-Catalyzed C-H Activation/Cyclization of Indoles and Pyrroles:Divergent Synthesis of Heterocycles", 《J. ORG. CHEM.》 * |
| ZI-JUN WU等: "A Cascade C–H-Func tionalization/Cyclization Reaction of Indoles with α-Halo or α-Sulfonyloxy Ketones for the Synthesis of Dihydropyrimidoindolone Derivatives", 《EUR. J. ORG. CHEM.》 * |
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| CN109232585A (en) * | 2018-11-29 | 2019-01-18 | 青岛科技大学 | A kind of preparation method of polysubstituted pyrimidine and two indolone derivatives |
| CN109232585B (en) * | 2018-11-29 | 2021-01-26 | 青岛科技大学 | Preparation method of polysubstituted pyrimido-diindolone derivative |
| CN110526852A (en) * | 2019-09-18 | 2019-12-03 | 湖北斯柏生物科技有限公司 | A kind of preparation method of indoles |
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