CN109705052A - A method of preparing 1,4- dihydro oxazines - Google Patents
A method of preparing 1,4- dihydro oxazines Download PDFInfo
- Publication number
- CN109705052A CN109705052A CN201910075276.9A CN201910075276A CN109705052A CN 109705052 A CN109705052 A CN 109705052A CN 201910075276 A CN201910075276 A CN 201910075276A CN 109705052 A CN109705052 A CN 109705052A
- Authority
- CN
- China
- Prior art keywords
- reaction
- nitrae
- dihydro
- oxazines
- dihydro oxazines
- 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.)
- Granted
Links
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Isosorbide-5-Nitrae-dihydro oxazines method is prepared the invention discloses a kind of, using acyl group diazo compound derivative and acridine compounds as reaction substrate, with AgOTf and Cu (OAc)2For catalyst, with NaHCO3Isosorbide-5-Nitrae-dihydro oxazines is prepared by cycloaddition reaction in organic solvent for alkali.Method used in the present invention has the following characteristics that more economical, the later period function dough of reaction is easier to, reaction condition is mild, it can be carried out in air, catalyst amount is few, post-processing is easy, be conducive to the purifying and heavy industrialization application of product, a step function dough of commercial pharmaceutical is easier to carry out.Simultaneously, the raw materials such as reactant, catalyst that the present invention uses are cheap and easy to get, and reaction composition rationally, is not necessarily to ligand, Atom economy is high, reaction step is few, it is only necessary to which single step reaction can obtain higher yield, meet contemporary Green Chemistry and pharmaceutical chemical requirement and direction, suitable for screening the 1 of high activity, 4- dihydro oxazines class drug, gram-grade reaction also can be very good to realize, suitable for large-scale industrial production.
Description
Technical field
Isosorbide-5-Nitrae-dihydro oxazines method is prepared the present invention relates to a kind of, belongs to technical field of organic synthesis.
Background technique
1,4- dihydro oxazines is core knot generally existing in many natural products, biologically active drug and agricultural chemicals
Structure.Significantly, Isosorbide-5-Nitrae-dihydro oxazines is often referred to as the skeleton to enjoy privilege in pharmaceutical chemistry, new for finding and optimizing
Synthetic drug molecule.Isosorbide-5-Nitrae-dihydro oxazines also acts as composite structure unit useful in heterocycle building, it is also possible to make catalytic body
Additive in system.Currently, preparing Isosorbide-5-Nitrae-dihydro oxazines method has severe reaction conditions, raw material prepares cumbersome, raw material dosage
Greatly, the disadvantages of substrate spectrum is narrow, low yield.Such as:
(1) Siegfried et al. reports that amino acetylene hydrocarbon compound prepares Isosorbide-5-Nitrae-dihydro oxazines by intramolecular nucleophilic addition cyclisation,
But amino acetylene hydrocarbon compound raw material needs one or more steps reaction next pre-prepared, so that the range of substrate be made to narrow, be prepared into
Originally high (referring to: Blechert, S.,Angew. Chem. Int. Ed. 2005, 117, 7972.)；
(2) Urabe et al. reports halogenated alkynes and hydroxylamine compounds and prepares 1,4- dihydro by intermolecular cycloaddition reaction
Oxazines, but reaction need to carry out at a higher temperature, and reaction be not suitable for polysubstituted oxazines ring preparation (referring to:
Urabe, H., J. Am. Chem. Soc. 2008, 130, 1820.).
Therefore, it is necessary to which to research and develop a kind of raw material sources abundant, reaction condition is mild, at low cost, safe and environment-friendly, operation
Easy, yield is high preparation method is effectively synthesized 1,4- dihydro oxazines compound.
Summary of the invention
Isosorbide-5-Nitrae-dihydro oxazines method, core Isosorbide-5-Nitrae-dihydro oxazines ring structure are prepared the object of the present invention is to provide a kind of
Degree of modification is high, provides a kind of useful approach for preparing non-polymeric polysubstituted Isosorbide-5-Nitrae-dihydro oxazine compound；And
The reaction condition is mild, easy to operate, convenient for later period functional compound at potential macromolecular compound.
To achieve the above object of the invention, the technical solution adopted by the present invention is that:
A method of Isosorbide-5-Nitrae-dihydro oxazines being prepared, using acyl group diazo compound derivative and acridine derivatives as reaction substrate, with Lewis
For catalyst in organic solvent, Isosorbide-5-Nitrae-dihydro is prepared by cycloaddition reaction using alkali as additive in acid and transition metal
Oxazines；
The chemical structural formula of the acyl group diazo compound derivative is as follows:
、 、 、；
The general structure of the acridine derivatives is as follows:
In formula, R1Selected from chlorine, fluorine, chlorine, bromine or acetoxyl group, such as R1The chlorine that can be ortho position substitution, is also possible to meta position
Substituted chlorine, or fluorine, chlorine, bromine, acetoxyl group, methoxyl group that contraposition replaces；
The chemical structural formula of the 1,4- dihydro oxazines is as follows:
Wherein R2From acyl group diazo compound derivative.
In above-mentioned technical proposal, the reaction temperature of the cycloaddition reaction is 20~60 DEG C, and the reaction time is 12~24 small
When；Preferably, the reaction temperature of the cycloaddition reaction is 40 DEG C, and the reaction time is 12 hours.
In above-mentioned technical proposal, the Lewis acid is boron trifluoride ether or AgOTf；The transition metal is mantoquita；Institute
Stating alkali is sodium salt；The organic solvent is methylene chloride, ethyl acetate, 1,2- dichloroethanes, benzene, toluene, one in hexamethylene
Kind or several, preferably 1,2- dichloroethanes；Preferably, the sodium salt is NaHCO3Or Na2CO3；The mantoquita is Cu (OAc)2
Or Cu2SO4。
In above-mentioned technical proposal, the cycloaddition reaction carries out in air；After reaction, solvent is removed, silica gel is inhaled
It is attached that product 1,4- dihydro oxazines can be obtained by column chromatography.
In above-mentioned technical proposal, the dosage of the Lewis acid is the 5% ~ 20% of acyl group diazo compound derivative mole；The mistake
The dosage for crossing metal is the 5% ~ 20% of acyl group diazo compound derivative mole；The base amount is acyl group diazo compound derivative mole
0.5 ~ 2 times；The acridine compounds dosage is attached most importance to 3 times of nitrone compound mole；Preferably, the use of the Lewis acid
Amount is the 15% of acyl group diazo compound derivative mole；The dosage of the transition metal is the 10% of acyl group diazo compound derivative mole；
The base amount is 2 times of acyl group diazo compound derivative mole.
The invention discloses transition metal as catalyst is preparing the application in 1,4- dihydro oxazines.
In above-mentioned technical proposal, Isosorbide-5-Nitrae-dihydro oxazines is prepared in the presence of Lewis acid, with acyl group diazo compound derivative and acridine
Derivative is reaction substrate, using alkali as additive, is carried out in organic solvent.
In above-mentioned technical proposal, the Lewis acid is boron trifluoride ether or AgOTf；The transition metal is mantoquita；Institute
Stating alkali is sodium salt；The organic solvent is methylene chloride, ethyl acetate, 1,2- dichloroethanes, benzene, toluene, one in hexamethylene
Kind or several, preferably 1,2- dichloroethanes；Preferably, the sodium salt is NaHCO3Or Na2CO3；The mantoquita is Cu (OAc)2
Or Cu2SO4。
Cycloaddition reaction of the invention carries out in air.Solvent, silica gel absorption are removed with Rotary Evaporators, finally uses second
The mixed solvent of acetoacetic ester and petroleum ether, which carries out simple column chromatography, can obtain product 1,4- dihydro oxazines.Therefore the present invention also public affairs
The 1,4- dihydro oxazines being prepared according to the above method is opened.
Due to the application of the above technical scheme, compared with the prior art, the invention has the following advantages:
1. the present invention uses AgOTf or Cu (OAc)2For catalyst, with NaHCO3Carbonyl diazonium compound and a word used for translation are realized for alkali
The cycloaddition reaction of acridine compound prepares Isosorbide-5-Nitrae-dihydro oxazines compound, and raw material in the prior art is pre-prepared, raw material is malicious
Property compared with condition harshness greatly, react that more economical, substrate universality is wider, raw material is easy to get, later period function dough is easier.Furthermore
Compared to the method for preparing polysubstituted Isosorbide-5-Nitrae-dihydro oxazines compound before and using Noble Metal Rhodium, present invention uses more cheap
Copper and silver, this substantially reduces preparation cost.
2. method disclosed by the invention is compared with prior art, reaction condition is mild, can carry out in air, and catalyst is used
Amount is few, and post-processing is easy, is conducive to the purifying and heavy industrialization application of product, a step function dough of commercial pharmaceutical is more
Easily carry out.
3. the raw materials such as the reactant that the present invention uses, catalyst are cheap and easy to get, reaction composition rationally, is not necessarily to ligand, atom
Economy is high, and reaction step is few, it is only necessary to which single step reaction can obtain higher yield, meet contemporary Green Chemistry and pharmaceutical chemistry
Requirement and direction, gram-grade reaction also can be very good to realize, be suitable for large-scale industrial production.
Specific embodiment
The present invention will be further described below with reference to examples:
Acyl group diazo compound derivative of the invention, acridine compounds, catalyst, additive are all market-oriented commodity, can directly be bought,
Diazonium carbonyl compound can also be obtained by the carbonyls of the marketization and the p-toluene sulfonyt azide reaction synthesis of the marketization
Object can also obtain acridine by the aromatic olefin of the marketization and the chloramine-T reaction synthesis of the marketization.
Embodiment one
It is sequentially loaded into reaction flask compound 1a (0.2 mmol, 28.4 mg), compound 2a (0.6 mmol, 163.8 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3a, yield 70% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H), 7.35 (ddd, J =
8.3, 6.7, 4.6 Hz, 5H), 7.13 (dd, J = 7.5, 1.8 Hz, 2H), 4.36 (dd, J = 10.2,
2.9 Hz, 1H), 3.85 (s, 3H), 2.85 (dd, J = 14.6, 10.3 Hz, 1H), 2.45 (s, 3H),
2.26 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.12, 154.17, 144.66, 136.27,
134.59, 129.92, 128.91, 128.79, 128.28, 125.91, 106.08, 75.22, 52.06, 48.31,
21.67, 18.48; HRMS (ESI-TOF): Anal. Calcd. For C20H21NO5S: 410.1033, Found:
410.1032 (M+Na+); IR (neat, cm-1): υ 2917, 2849, 1725, 1627, 1440,1356, 1304,
1163, 1117, 771, 747, 669。
Embodiment two
Compound 1b is sequentially loaded into reaction flask, and (7 mmol, 1.1 g), and (21 mmol, 1.9 g), AgOTf by compound 2a
(0.7 mmol, 0.2 g), Cu(OAc)2(1.1 mmol, 0.2 g), NaHCO3(14 mmol, 1.2 g), DCE (14
mL).Then after the system heats about 12 hours under the conditions of 40 DEG C in air, solvent, silica gel absorption are removed with Rotary Evaporators,
Product 3b, yield 73% can be obtained by simple column chromatography.The main test data of obtained product is as follows, passes through analysis
It is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.2 Hz, 2H), 7.48 – 7.26 (m,
5H), 7.14 (dd, J = 7.5, 1.6 Hz, 2H), 4.40 (dd, J = 10.2, 2.8 Hz,1H), 4.34
(dt, J = 13.8, 6.9 Hz, 2H), 3.82 (dd, J = 14.6, 3.0 Hz, 1H), 2.84 (dd, J =
14.6, 10.3 Hz, 1H), 2.45 (s, 3H), 2.26 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 165.70, 153.81, 144.58, 136.37, 134.65, 129.86,
128.87, 128.77, 128.34, 125.93, 106.29, 75.22, 61.20, 48.34, 21.67, 18.53,
14.25. HRMS (ESI-TOF): Anal. Calcd. For C21H23NO5S: 424.1189, Found: 424.1197
(M+Na+); IR (neat, cm-1): υ 2927, 2850, 1717, 1625, 1448, 1356, 1304, 1162,
1113, 772, 747, 666。
Embodiment three
It is sequentially loaded into reaction flask compound 1c (0.2 mmol, 25.2 mg), compound 2a (0.6 mmol, 163.9 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3a, yield 80% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.0
Hz, 2H), 7.36 – 7.31 (m, 3H), 7.04 – 6.98 (m, 2H), 4.03 (dd, J = 14.9, 3.1
Hz, 1H), 3.72 (dd, J = 10.6, 3.1 Hz, 1H), 2.96 (dd, J = 14.9, 10.6 Hz, 1H),
2.48 (s, 3H), 2.47 (s, 3H), 2.14 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 197.15,
152.15, 144.63, 135.52, 133.03, 129.75, 128.49, 128.34, 127.88, 125.20,
114.29, 72.95, 47.62, 28.30, 21.24, 17.82; HRMS (ESI-TOF): Anal. Calcd. For
C20H21NO4S: 394.1083, Found: 394.1112 (M+Na+); IR (neat, cm-1): υ 2924, 1687,
1594, 1352, 1243, 1162, 1130, 1067, 943, 777, 757, 667, 651。
Example IV
It is sequentially loaded into reaction flask compound 1d (0.2 mmol, 31.2 mg), compound 2a (0.6 mmol, 184.2 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3d, yield 82% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.39 – 7.31 (m,
4H), 7.12 – 7.07 (m, 2H), 4.45 (dd, J = 10.2, 2.9 Hz, 1H), 4.33 (qd, J = 7.1,
1.9 Hz, 2H), 3.78 (dd, J = 14.6, 3.0 Hz, 1H), 2.79 (dd, J = 14.6, 10.2 Hz,
1H), 2.45 (s, 3H), 2.26 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 165.53, 153.59, 144.66, 134.90, 134.72, 134.63, 129.87, 128.99,
128.30, 127.30, 106.38, 74.66, 61.22, 48.24, 21.66, 18.50, 14.23; HRMS (ESI-
TOF): Anal. Calcd. For C21H22ClNO5S: 458.0799, Found: 458.0803 (M+Na+); IR
(neat, cm-1): υ 2924, 1716, 1618, 1493, 1329, 1293, 1156, 1092, 1053, 902,
833, 775, 668。
Embodiment five
It is sequentially loaded into reaction flask compound 1d (0.2 mmol, 31.2 mg), compound 2a (0.6 mmol, 210.6 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3e, yield 81% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.51 – 7.46 (m,
2H), 7.37 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 4.44 (dd, J = 10.2,
2.9 Hz, 1H), 4.33 (qd, J = 7.1, 2.0 Hz, 2H), 3.78 (dd, J = 14.6, 3.0 Hz, 1H),
2.78 (dd, J = 14.6, 10.2 Hz, 1H), 2.45 (s, 3H), 2.26 (s, 3H), 1.36 (t, J =
7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 165.04, 153.11, 144.19, 134.94,
134.15, 131.47, 129.39, 127.83, 127.10, 122.37, 105.91, 74.22, 60.74, 47.69,
21.18, 18.01, 13.74; HRMS (ESI-TOF): Anal. Calcd. For C21H22BrNO5S: 502.0294,
Found: 504.0275 (M+Na+); IR (neat, cm-1): υ 2922, 1716, 1617, 1329, 1293,
1155, 1090, 1052, 1009, 967, 836, 774, 667。
Embodiment six
It is sequentially loaded into reaction flask compound 1b (0.2 mmol, 31.2 mg), compound 2d (0.6 mmol, 184.2 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3f, yield 74% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.91 – 7.87 (m, 2H), 7.36 – 7.31 (m, 3H),
7.29 – 7.25 (m, 3H), 4.98 (dd, J = 10.2, 3.3 Hz, 1H), 4.34 (q, J = 7.1 Hz,
2H), 4.05 (dd, J = 14.6, 3.3 Hz, 1H), 2.72 (dd, J = 14.6, 10.2 Hz, 1H), 2.43
(s, 3H), 2.29 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
165.60, 153.53, 144.48, 134.68, 134.23, 131.86, 129.80, 129.72, 128.49,
127.32, 106.48, 72.43, 61.24, 46.29, 21.65, 18.41, 14.25; HRMS (ESI-TOF):
Anal. Calcd. For C21H22ClNO5S: 458.0799, Found: 458.0803 (M+Na+); IR (neat, cm-1): υ 2919, 2850, 1714, 1626, 1439, 1302, 1157, 1106, 1055, 964, 906, 760,
666。
Embodiment seven
It is sequentially loaded into reaction flask compound 1b (0.2 mmol, 31.2 mg), compound 2d (0.6 mmol, 173.4 mg),
AgOTf (0.03 mmol, 7.7 mg), Cu(OAc)2(0.02 mmol, 3.6 mg), NaHCO3(0.4 mmol, 33.6
Mg), DCE (0.4 mL).Then it after the system heats about 12 hours under the conditions of 40 DEG C in air, is removed with Rotary Evaporators molten
Agent, silica gel absorption can obtain product 3g, yield 76% by simple column chromatography.The main test data of obtained product is such as
Under, by analyzing it is found that practical synthetic product is consistent with theory analysis.
1H NMR (400 MHz, CDCl3) δ 7.96 – 7.90 (m, 2H), 7.35 (dd, J = 5.7, 3.7
Hz, 3H), 7.16 (dd, J = 7.5, 1.8 Hz, 2H), 7.05 – 7.00 (m, 2H), 4.46 (dd, J =
10.2, 2.9 Hz, 1H), 4.34 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 3.80 (dd, J =
14.6, 3.0 Hz, 1H), 2.83 (dd, J = 14.6, 10.2 Hz, 1H), 2.26 (s, 3H), 1.38 (t, J
= 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 165.29, 163.16, 153.26, 135.94,
130.04, 128.59, 128.39, 128.29, 125.47, 113.92, 105.86, 76.90, 76.58, 76.26,
74.77, 60.70, 55.24, 47.81, 18.04, 13.78.; HRMS (ESI-TOF): Anal. Calcd. For
C21H23NO6S: 440.1138, Found: 440.1146 (M+Na+); IR (neat, cm-1): υ 2929, 1713,
1629, 1594, 1497, 1356, 1260, 1153, 1104, 1066, 1022, 966, 904, 805, 766,
749, 699, 671。
Claims (10)
1. a kind of prepare Isosorbide-5-Nitrae-dihydro oxazines method, it is characterised in that: with acyl group diazo compound derivative and acridine derivatives be anti-
Substrate is answered, using Lewis acid and transition metal as catalyst, using alkali as additive, in organic solvent, by cycloaddition reaction system
It is standby to obtain 1,4- dihydro oxazines；
The chemical structural formula of the acyl group diazo compound derivative is as follows:
、 、 、；
The general structure of the acridine derivatives is as follows:
In formula, R1Selected from chlorine, fluorine, chlorine, bromine, methoxyl group or acetoxyl group；
The chemical structural formula of the 1,4- dihydro oxazines is as follows:
。
2. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 1, it is characterised in that: the reaction of the cycloaddition reaction
Temperature is 20~60 DEG C, and the reaction time is 12~24 hours.
3. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 2, it is characterised in that: the reaction of the cycloaddition reaction
Temperature is 40 DEG C, and the reaction time is 12 hours.
4. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 1, it is characterised in that: the Lewis acid is borontrifluoride
Borate ether or AgOTf；The transition metal is mantoquita；The alkali is sodium salt；The organic solvent is methylene chloride, acetic acid second
One or more of ester, 1,2- dichloroethanes, benzene, toluene, hexamethylene.
5. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 4, it is characterised in that: the sodium salt is NaHCO3Or
Na2CO3；The mantoquita is Cu (OAc)2Or Cu2SO4。
6. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 1, it is characterised in that: the cycloaddition reaction is in air
Middle progress；After reaction, it chromatographs to obtain product Isosorbide-5-Nitrae-dihydro oxazines by column after removing solvent, silica gel absorption.
7. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 1, it is characterised in that: the dosage of the Lewis acid is
The 5% ~ 20% of acyl group diazo compound derivative mole；The dosage of the transition metal be acyl group diazo compound derivative mole 5% ~
20%；The base amount is 0.5 ~ 2 times of acyl group diazo compound derivative mole；The acridine compounds dosage is attached most importance to nitrone
3 times for closing object mole.
8. preparing Isosorbide-5-Nitrae-dihydro oxazines method according to claim 7, it is characterised in that: the dosage of the Lewis acid is
The 15% of acyl group diazo compound derivative mole；The dosage of the transition metal is the 10% of acyl group diazo compound derivative mole；It is described
Base amount is 2 times of acyl group diazo compound derivative mole.
9. preparing the 1,4- dihydro oxazines of the method preparation of 1,4- dihydro oxazines according to claim 1.
10. transition metal is preparing the application in 1,4- dihydro oxazines as catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910075276.9A CN109705052B (en) | 2019-01-25 | 2019-01-25 | Method for preparing 1, 4-dihydrooxazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910075276.9A CN109705052B (en) | 2019-01-25 | 2019-01-25 | Method for preparing 1, 4-dihydrooxazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109705052A true CN109705052A (en) | 2019-05-03 |
| CN109705052B CN109705052B (en) | 2020-12-08 |
Family
ID=66261857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910075276.9A Active CN109705052B (en) | 2019-01-25 | 2019-01-25 | Method for preparing 1, 4-dihydrooxazine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109705052B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003097618A1 (en) * | 2002-05-22 | 2003-11-27 | Glaxo Group Limited | Morpholinylmethylureas ccr-3 receptor antagonists |
| WO2006019975A1 (en) * | 2004-07-15 | 2006-02-23 | Amgen Inc. | 1,2,3,4-tetrahydropyrazin-2-yl acetamides and their use as bradykinin antagonists for the treatment of inflammation related disorders |
| CN101602741A (en) * | 2004-06-30 | 2009-12-16 | 先灵公司 | N-arylsulfonylheterocyamines amines as the replacement of inhibitors of gamma-secretase |
| CN101679324A (en) * | 2007-06-15 | 2010-03-24 | 田边三菱制药株式会社 | morpholine derivative |
| WO2011020806A1 (en) * | 2009-08-19 | 2011-02-24 | F. Hoffmann-La Roche Ag | 3-amino-5-phenyl-5,6-dihydro-2h-[1,4]oxazine derivatives |
| CN103562191A (en) * | 2011-03-16 | 2014-02-05 | 上海医药集团股份有限公司 | Nitrogen-containing saturated heterocyclic compound |
| CN104130204A (en) * | 2014-07-03 | 2014-11-05 | 浙江大学 | Method for preparing N-sulfonyl-1,4-oxazine derivative |
| CN104193695A (en) * | 2014-09-03 | 2014-12-10 | 哈尔滨工业大学 | Synthesis method of morpholine compounds |
-
2019
- 2019-01-25 CN CN201910075276.9A patent/CN109705052B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003097618A1 (en) * | 2002-05-22 | 2003-11-27 | Glaxo Group Limited | Morpholinylmethylureas ccr-3 receptor antagonists |
| CN101602741A (en) * | 2004-06-30 | 2009-12-16 | 先灵公司 | N-arylsulfonylheterocyamines amines as the replacement of inhibitors of gamma-secretase |
| WO2006019975A1 (en) * | 2004-07-15 | 2006-02-23 | Amgen Inc. | 1,2,3,4-tetrahydropyrazin-2-yl acetamides and their use as bradykinin antagonists for the treatment of inflammation related disorders |
| CN101679324A (en) * | 2007-06-15 | 2010-03-24 | 田边三菱制药株式会社 | morpholine derivative |
| WO2011020806A1 (en) * | 2009-08-19 | 2011-02-24 | F. Hoffmann-La Roche Ag | 3-amino-5-phenyl-5,6-dihydro-2h-[1,4]oxazine derivatives |
| CN103562191A (en) * | 2011-03-16 | 2014-02-05 | 上海医药集团股份有限公司 | Nitrogen-containing saturated heterocyclic compound |
| CN104130204A (en) * | 2014-07-03 | 2014-11-05 | 浙江大学 | Method for preparing N-sulfonyl-1,4-oxazine derivative |
| CN104193695A (en) * | 2014-09-03 | 2014-12-10 | 哈尔滨工业大学 | Synthesis method of morpholine compounds |
Non-Patent Citations (5)
| Title |
|---|
| JAMES L. DOUGLAS 等: "Nuclear analogs of β-lactam antibiotics. IX. Synthesis of 7-methoxy 2-isocephems and O-2 isocephems", 《CAN. J. CHEM.》 * |
| KUMAR, Y. C. SUNIL 等: "Effect of novel N-aryl sulfonamide substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| NIKOLAI V. ROSTOVSKII 等: "Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization", 《BEILSTEIN J ORG CHEM》 * |
| SANTA, Z 等: "Synthesis of enantiomerically pure 2-isoxacephems", 《MONATSHEFTE FUR CHEMIE》 * |
| 王剑: "4H-1,4-噁嗪的设计、合成及其转甲状腺素蛋白抑制活性的研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109705052B (en) | 2020-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gao et al. | Highly diastereo-and enantioselective synthesis of tetrahydrobenzo [b] azocines via palladium-catalyzed [4+ 4] cycloaddition | |
| Letessier et al. | First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline | |
| Hu et al. | Phosphine-catalyzed Rauhut-Currier domino reaction: a facile strategy for the construction of carbocyclic spirooxindoles skeletons. | |
| Zhang et al. | Highly efficient enantioselective synthesis of bispiro [benzofuran-oxindole/benzofuran-chromanone] s through organocatalytic inter-/intramolecular Michael cycloaddition | |
| Jia et al. | Cu (BTC)-MOF catalyzed multicomponent reaction to construct 1, 4-disubstituted-1, 2, 3-triazoles | |
| Wang et al. | The Divergent Cascade Reactions of Arylalkynols with Homopropargylic Amines or Electron-Deficient Olefins: Access to the Spiro-Isobenzofuran-b-pyrroloquinolines or Bridged-Isobenzofuran Polycycles | |
| CN103274987A (en) | 3,3-disubstituted oxoindole derivative, and synthetic method and application thereof | |
| Kowalski et al. | Ferrocenyl derivatives of pterocarpene and coumestan: Synthesis, structure and anticancer activity studies | |
| Yang et al. | Rhodium‐Catalyzed Denitrogenative [3+ 2] Cycloaddition: Access to Functionalized Hydroindolones and the Framework of Montanine‐Type Amaryllidaceae Alkaloids | |
| Gurumurthy et al. | A diastereoselective synthesis of tetrahydro-and dihydro-pyrido [2, 3-c] coumarin derivatives via a one-pot three-component Povarov reaction catalyzed by bismuth (III) chloride | |
| Chowdhury et al. | Syntheses of highly substituted furan and pyrrole derivatives via lithiated 3-aryl-1-methoxyallenes: application to the synthesis of codonopsinine | |
| Hu et al. | Exploratory studies en route to 5-alkyl-hyacinthacines: synthesis of 5-epi-(-)-hyacinthacine A3 and (-)-hyacinthacine A3 | |
| Pan et al. | Highly stereoselective synthesis of spirocyclopropylthiooxindoles and biological evaluation | |
| CN109705052A (en) | A method of preparing 1,4- dihydro oxazines | |
| CN111518086A (en) | Oxoindole-naphthofuran derivatives, preparation method and application thereof, and pharmaceutical composition and preparation containing same | |
| Wang et al. | Metal Alkoxide Promoted Regio‐and Stereoselective C O and C C Metathesis of Allenoates with Aldehydes | |
| Suzuki et al. | Tandem five membered-ring selective Prins reaction and Friedel–Crafts reaction | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| Gannarapu et al. | Construction of poly-N-heterocyclic scaffolds via the controlled reactivity of Cu-allenylidene intermediates | |
| Tan et al. | Synthetic studies towards the total synthesis of indole alkaloids containing indolyl lactam frameworks | |
| CN109678862B (en) | Preparation method of polysubstituted distyryl indole derivative | |
| Yadav et al. | Organocatalytic stereoselective aziridination of imines via ammonium ylides | |
| Jia et al. | Biology-Oriented Synthesis of Decahydro-4, 8-epoxyazulene Scaffolds | |
| Frichert et al. | Oxidation of the meroterpenoid (−)-terreumol c from the mushroom Tricholoma terreum: discovery of cytotoxic analogues | |
| CN108383760B (en) | Method for preparing fully-substituted amidine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |