CN110372708A - A kind of synthetic method of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound - Google Patents
A kind of synthetic method of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound Download PDFInfo
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- CN110372708A CN110372708A CN201910787861.1A CN201910787861A CN110372708A CN 110372708 A CN110372708 A CN 110372708A CN 201910787861 A CN201910787861 A CN 201910787861A CN 110372708 A CN110372708 A CN 110372708A
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- 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
Abstract
The invention discloses one kind 5HBenzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound synthetic method, which passes through tandem reaction between 2- Aryimidazole or 2- heteroaryl-imidazole azole compounds and 2- methene propiolactone class compound synthesis 5HBenzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound, the present invention has many advantages, such as easy to operate, mild condition, wide application range of substrates, is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of 5H- benzo [c] imidazo [1,2-a] azacyclo-
The synthetic method of heptene -6- carboxylic acid compound.
Background technique
It is well known that natural or artificial synthesized azepine and its benzo derivative usually have significant biology and
Pharmaceutical activity.On the other hand, imidazoles is then the important structural unit of numerous natural products, clinical medicine and N-heterocyclic carbine etc.,
There is important application value in fields such as organic chemistry, pharmaceutical chemistry and materials chemistries.In view of benzazepine and
The importance of glyoxaline structure skeleton, people have reason to believe that the hybrid molecule containing both dominance structure units will very simultaneously
The biology or physical characteristic that enhance or cooperate with may be shown, so that the exploitation for high potency drugs and new material provides new think of
Road and chance.It should be pointed out that still lacking at present effective although such hybrid molecule has broad application prospects
Preparation method.Therefore, it studies and develops from raw material cheap and easy to get, via easy operating procedure synthesis 5H- benzo [c]
The new method of imidazo [1,2-a] azepine -6- carboxylic acid compound not only has important theory significance, but also has
There is important application value.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of 5H- benzo [c] imidazo [1,2-a] azepine -6-
The synthetic method of carboxylic acid compound, the synthetic method pass through 2- Aryimidazole or 2- heteroaryl-imidazole azole compounds and 2- methylene
Tandem reaction between base propiolactone class compound synthesizes 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acids
Compound has many advantages, such as easy to operate, mild condition, wide application range of substrates, is suitable for industrialized production.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of 5H- benzo [c] imidazo [1,2-a]
The synthetic method of azepine -6- carboxylic acid compound, it is characterised in that specific synthesis process are as follows: by 2- Aryimidazole or 2-
Heteroaryl-imidazole azole compounds 1 and 2- methene propiolactone class compound 2 are dissolved in solvent, and catalyst and oxidation is then added
Agent reacts in 80-120 DEG C and 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound 3, the synthesis is made
Reaction equation in method are as follows:
Wherein R1For hydrogen, fluorine, chlorine, bromine, trifluoromethyl, C1-4Alkyl or C1-4Alkoxy, R2For hydrogen, C1-4Alkyl, C1-4Alcoxyl
Base, phenyl or substituted-phenyl, R3For C1-16Alkyl replaces alkyl, phenyl or substituted-phenyl, and replacing the substituent group of alkyl is phenyl
Or substituted-phenyl, the substituent group on the substituted-phenyl phenyl ring is fluorine, chlorine, bromine, C1-4Alkyl, C1-4Alkoxy or cyano, X are
C or N, catalyst are that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer, bis- (the 4- isopropyl methyl phenyl) rutheniums of dichloro
(II), dichloro (pentamethylcyclopentadiene base) closes iridium (III) dimer or pentamethylcyclopentadiene base rhodium acetate (III), oxidation
Agent be silver acetate or silver carbonate, solvent 1,2- dichloroethanes, methanol, hexafluoroisopropanol, toluene, acetonitrile, methylene chloride or 1,
4- dioxane.
Further preferably, the 2- Aryimidazole or 2- heteroaryl-imidazole azole compounds 1,2- methene propiolactone class
Closing the ratio between amount for the substance that feeds intake of object 2, catalyst and oxidant is 1:1-2:0.025:1-2.
A kind of synthetic method of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound, feature
It is specific synthesis process are as follows: 2- aryl imidazoles 4 and 2- methene propiolactone class compound 2 are dissolved in solvent,
Then catalyst and oxidant is added, is reacted in 80-120 DEG C and 5H- benzo [c] imidazo [1,2-a] azepine -6- is made
Carboxylic acid compound 5, the reaction equation in the synthetic method are as follows:
Wherein R2For hydrogen, C1-4Alkyl, C1-4Alkoxy, phenyl or substituted-phenyl, R3For C1-16Alkyl replaces alkyl, benzene
Base or substituted-phenyl, replacing the substituent group of alkyl is phenyl or substituted-phenyl, and the substituent group on the substituted-phenyl phenyl ring is
Fluorine, chlorine, bromine, C1-4Alkyl, C1-4Alkoxy or cyano, catalyst are that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimerization
Bis- (the 4- isopropyl methyl phenyl) rutheniums (II) of body, dichloro, dichloro (pentamethylcyclopentadiene base) close iridium (III) dimer or five first
Cyclopentadienyl group rhodium acetate (III), oxidant are silver acetate or silver carbonate, and solvent 1,2- dichloroethanes, methanol, hexafluoro are different
Propyl alcohol, toluene, acetonitrile, methylene chloride or 1,4- dioxane.
Further preferably, the 2- aryl imidazoles 4,2- methene propiolactone class compound 2, catalyst and
The ratio between amount for the substance that feeds intake of oxidant is 1:1-2:0.025:1-2.
Compared with the prior art, the present invention has the following advantages: (1) synthesis process simple, efficient, anti-by one pot of series connection
5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound should be directly obtained；(2) reaction condition is mild, behaviour
Make easy；(3) substrate is applied widely.Therefore, the present invention is 5H- benzo [c] imidazo [1,2-a] azepine -6-
The synthesis of carboxylic acid compound provide it is a kind of be simple and efficient, economical and practical new method.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3a
(72.4mg, 73%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.78-1.87(m,2H),
2.18-2.23 (m, 1H), 2.41-2.46 (m, 1H), 5.62 (t, J=6.6Hz, 1H), 6.96 (d, J=7.2Hz, 2H), 7.12
(t, J=7.2Hz, 1H), 7.17-7.18 (m, 3H), 7.45-7.48 (m, 2H), 7.54 (t, J=7.8Hz, 1H), 7.62 (d, J
=7.2Hz, 1H), 7.87 (s, 1H), 8.17 (d, J=7.8Hz, 1H), 13.28 (br s, 1H)13C NMR(150MHz,DMSO-
d6)δ:32.2,34.4,54.7,124.0,126.4,128.4,128.8,128.9,129.6,130.3,130.48,130.51,
132.7,133.4,139.6,140.8,144.3,167.3.HRMS calcd for C21H17N2O2:329.1296[M-H]-,
found:329.1296。
Embodiment 2
1a (43.3mg, 0.3mmol), 1,2- dichloroethanes (3mL), 2a are sequentially added into the pressure pipe of 15mL
(56.5mg, 0.3mmol), dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer (4.7mg, 0.0075mmol) and vinegar
Pressure pipe, is then sealed and placed in 100 DEG C of oil baths and reacts 10h by sour silver (50.1mg, 0.3mmol).It is cold to after reaction
But it to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3a (30.7mg, 31%).
Embodiment 3
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methanol (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(24.8mg, 25%).
Embodiment 4
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), hexafluoroisopropanol (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(25.8mg, 26%).
Embodiment 5
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), toluene (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(29.7mg, 30%).
Embodiment 6
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), acetonitrile (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(11.9mg, 12%).
Embodiment 7
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(32.7mg, 33%).
Embodiment 8
1a (43.3mg, 0.3mmol), 1,4- dioxane (3mL), 2a are sequentially added into the pressure pipe of 15mL
(56.5mg, 0.3mmol), dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer (4.7mg, 0.0075mmol) and vinegar
Pressure pipe, is then sealed and placed in 100 DEG C of oil baths and reacts 10h by sour silver (50.1mg, 0.3mmol).It is cold to after reaction
But it to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3a (13.9mg, 14%).
Embodiment 9
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver carbonate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (82.7mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(17.8mg, 18%).
Embodiment 10
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), bis- (the 4- isopropyl methyl phenyl) rutheniums (II) (4.6mg, 0.0075mmol) of dichloro and silver acetate (50.1mg,
0.3mmol), then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h.To after reaction, be cooled to room temperature, take out
Filter, be spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) obtain white solid product 3a (10.9mg,
11%).
Embodiment 11
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes iridium (III) dimer (6.0mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (50.1mg, 0.3mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(9.9mg, 10%).
Embodiment 12
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), pentamethylcyclopentadiene base rhodium acetate (III) (2.7mg, 0.0075mmol) and silver acetate (50.1mg,
0.3mmol), then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h.To after reaction, be cooled to room temperature, take out
Filter, be spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) obtain white solid product 3a (30.7mg,
31%).
Embodiment 13
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (75.1mg, 0.45mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3a
(54.5mg, 55%).
Embodiment 14
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (56.5mg,
0.3mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3a
(63.4mg, 64%).
Embodiment 15
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (112.9mg,
0.6mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3a
(66.4mg, 67%).
Embodiment 16
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 80 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, be cooled to
Room temperature is filtered, is spin-dried for, and is crossed silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and is obtained white solid product 3a
(64.4mg, 65%).
Embodiment 17
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 120 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3a
(62.4mg, 63%).
Embodiment 18
Sequentially added into the pressure pipe of 15mL 1b (47.5mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3b
(70.3mg, 68%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.73-1.85(m,2H),
2.15-2.19 (m, 1H), 2.36 (s, 3H), 2.39-2.44 (m, 1H), 5.55-5.57 (m, 1H), 6.95 (d, J=7.2Hz,
2H), 7.10-7.12 (m, 2H), 7.18 (t, J=7.8Hz, 2H), 7.34 (d, J=8.4Hz, 1H), 7.39-7.41 (m, 2H),
7.78 (s, 1H), 8.03 (d, J=7.8Hz, 1H), 13.13 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:21.0,
32.2,34.4,54.6,123.8,126.4,128.0,128.4,128.8,129.4,130.3,131.3,132.9,133.1,
138.5,139.8,140.8,144.4,167.3.HRMS calcd for C22H19N2O2:343.1452[M-H]-,found:
343.1450。
Embodiment 19
Sequentially added into the pressure pipe of 15mL 1c (60.1mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3c
(77.7mg, 67%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.33(s,9H),1.75-
1.85 (m, 2H), 2.16-2.21 (m, 1H), 2.39-2.44 (m, 1H), 5.54-5.57 (m, 1H), 6.97 (d, J=7.2Hz,
2H), 7.10-7.13 (m, 2H), 7.19 (t, J=7.2Hz, 2H), 7.38 (s, 1H), 7.56 (dd, J1=7.8Hz, J2=
1.8Hz, 1H), 7.61 (d, J=1.8Hz, 1H), 7.87 (s, 1H), 8.07 (d, J=8.4Hz, 1H), 13.09 (br s, 1H)
.13C NMR(150MHz,DMSO-d6)δ:31.4,32.2,34.4,34.9,54.6,123.8,126.5,127.6,128.0,
128.5,128.7,128.8,129.4,129.5,130.1,132.7,140.3,140.8,144.3,151.5,167.4.HRMS
calcd for C25H25N2O2:385.1922[M-H]-,385.1920。
Embodiment 20
Sequentially added into the pressure pipe of 15mL 1d (52.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3d
(68.1mg, 63%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.77-1.85(m,2H),
2.17-2.22 (m, 1H), 2.41-2.46 (m, 1H), 3.84 (s, 3H), 5.55-5.58 (m, 1H), 6.96 (d, J=7.2Hz,
2H), 7.11-7.13 (m, 3H), 7.19 (t, J=7.2Hz, 2H), 7.22 (d, J=1.8Hz, 1H), 7.39 (s, 1H), 7.84
(s, 1H), 8.05 (d, J=9.0Hz, 1H), 13.24 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:32.2,34.2,
54.6,55.9,116.4,117.1,123.1,123.5,126.4,128.4,128.7,128.8,130.5,132.0,133.4,
139.7,140.8,144.2,159.6,167.3.HRMS calcd for C22H19N2O3:359.1401[M-H]-,found:
359.1401。
Embodiment 21
Sequentially added into the pressure pipe of 15mL 1e (48.6mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3e
(57.5mg, 55%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.76-1.90(m,2H),
2.19-2.24 (m, 1H), 2.42-2.48 (m, 1H), 5.61-5.64 (m, 1H), 6.97 (d, J=7.2Hz, 2H), 7.13 (t, J
=7.2Hz, 1H), 7.17-7.21 (m, 3H), 7.40 (td, J1=8.4Hz, J2=2.4Hz, 1H), 7.45 (s, 1H), 7.56
(dd,J1=9.6Hz, J2=2.4Hz, 1H), 7.86 (s, 1H), 8.17-8.20 (m, 1H), 13.38 (br s, 1H)13C NMR
(150MHz,DMSO-d6)δ:32.2,34.4,54.6,117.6(d,2JC-F=21.5Hz), 118.4 (d,2JC-F=23.6Hz),
124.0,126.4,127.2(d,4JC-F=2.6Hz), 128.4,128.8,129.6,131.3 (d,3JC-F=8.0Hz), 132.6
(d,3JC-F=9.3Hz), 134.6,138.4,140.7,143.6,162.0 (d,1JC-F=244.5Hz), 167.1.19F NMR
(565MHz,DMSO-d6)δ:-113.43.HRMS calcd for C21H16FN2O2:347.1207[M-H]-,found:
347.1197。
Embodiment 22
Sequentially added into the pressure pipe of 15mL 1f (53.6mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3f
(69.0mg, 63%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.73-1.87(m,2H),
2.14-2.21 (m, 1H), 2.39-2.47 (m, 1H), 5.58-5.62 (m, 1H), 6.96 (d, J=7.2Hz, 2H), 7.12 (t, J
=7.2Hz, 1H), 7.17-7.21 (m, 3H), 7.47 (s, 1H), 7.57 (d, J=6.4Hz, 1H), 7.77 (d, J=2.0Hz,
1H), 7.82 (s, 1H), 8.12 (d, J=6.0Hz, 1H), 13.24 (br s, 1H)13C NMR(150MHz,CF3CO2D)δ:
30.6,31.2,57.8,119.0,120.4,124.0,126.6,127.5,128.4,127.9,131.6,132.2,132.8,
132.9,137.9,140.7,140.8,141.5,169.0.HRMS calcd for C21H16ClN2O2:363.0906[M-H]-,
found:363.0904。
Embodiment 23
Sequentially added into the pressure pipe of 15mL 1g (66.9mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3g
(83.5mg, 68%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.74-1.88(m,2H),
2.14-2.22 (m, 1H), 2.39-2.47 (m, 1H), 5.57-5.61 (m, 1H), 6.97 (d, J=7.2Hz, 2H), 7.12 (t, J
=7.2Hz, 1H), 7.17-7.21 (m, 3H), 7.46 (s, 1H), 7.70 (dd, J1=8.4Hz, J2=2.0Hz, 1H), 7.82 (s,
1H), 7.90 (d, J=2.0Hz, 1H), 8.05 (d, J=8.4Hz, 1H), 13.26 (br s, 1H)13C NMR(150MHz,
DMSO-d6)δ:32.1,34.6,54.7,121.8,124.4,126.5,128.4,128.8,129.6,129.9,130.7,
132.4,133.0,134.5,134.8,138.3,140.7,143.5,167.1.HRMS calcd for C21H16BrN2O2:
407.0401[M-H]-,found:407.0397。
Embodiment 24
Sequentially added into the pressure pipe of 15mL 1h (63.7mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3h
(61.0mg, 51%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.75-1.78(m,1H),
1.85-1.89 (m, 1H), 2.18-2.21 (m, 1H), 2.42-2.47 (m, 1H), 5.64-5.66 (m, 1H), 6.97 (d, J=
7.2Hz, 2H), 7.12 (t, J=7.2Hz, 1H), 7.19 (t, J=7.2Hz, 2H), 7.24 (s, 1H), 7.54 (s, 1H), 7.85
(d, J=7.8Hz, 1H), 7.96 (s, 1H), 8.07 (s, 1H), 8.33 (d, J=7.8Hz, 1H), 13.33 (br s, 1H)13C
NMR(150MHz,DMSO-d6)δ:32.1,34.8,54.9,124.3(q,1JC-F=270.9Hz), 125.0,126.5,128.4,
128.8,128.9(q,2JC-F=29.6Hz), 129.7,130.4,131.0,133.8,134.8,138.3,140.6,143.1,
167.1.19F NMR(376MHz,DMSO-d6)δ:-61.19.HRMS calcd for C22H16F3N2O2:397.1169[M-H]-,
found:397.1169。
Embodiment 25
Sequentially added into the pressure pipe of 15mL 1i (47.5mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3i
(48.6mg, 47%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.76-1.86(m,2H),
2.17-2.24 (m, 1H), 2.37-2.44 (m, 4H), 5.57 (t, J=7.6Hz, 1H), 6.96 (d, J=7.2Hz, 2H), 7.10-
7.13 (m, 2H), 7.19 (t, J=7.2Hz, 2H), 7.28 (d, J=8.0Hz, 1H), 7.41 (s, 1H), 7.49 (d, J=
7.6Hz,1H),7.81(s,1H),7.96(s,1H),13.07(br s,1H).13C NMR(150MHz,DMSO-d6)δ:21.5,
32.2,34.4,54.7,123.9,126.4,127.9,128.4,128.8,129.2,129.5,129.8,130.4,132.8,
139.6,140.2,140.8,144.3,167.4.HRMS calcd for C22H19N2O2:343.1452[M-H]-,found:
343.1445。
Embodiment 26
Sequentially added into the pressure pipe of 15mL 1j (52.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3j
(29.2mg, 27%) and white solid product 3j'(30.3mg, 28%).
The characterize data of compound 3j is as follows:1H NMR(400MHz,DMSO-d6)δ:1.77-1.84(m,2H),2.16-
2.24 (m, 1H), 2.37-2.45 (m, 1H), 3.87 (s, 3H), 5.55-5.59 (m, 1H), 6.97 (d, J=7.2Hz, 2H),
7.04(dd,J1=8.8Hz, J2=2.8Hz, 1H), 7.10-7.14 (m, 2H), 7.19 (t, J=7.2Hz, 2H), 7.42 (s,
1H), 7.56 (d, J=8.8Hz, 1H), 7.64 (d, J=2.8Hz, 1H), 7.80 (s, 1H), 12.95 (br s, 1H)13C NMR
(150MHz,CF3CO2D)δ:30.5,31.3,55.2,58.0,114.2,118.5,120.1,122.4,123.9,124.2,
126.5,127.5,127.7,128.4,135.7,138.2,141.9,142.3,169.7.HRMS calcd for
C22H19N2O3:359.1401[M-H]-,found:359.1402。
The characterize data of compound 3j' is as follows:1H NMR(400MHz,DMSO-d6)δ:1.78-1.87(m,2H),2.15-
2.23 (m, 1H), 2.39-2.47 (m, 1H), 3.92 (s, 3H), 5.58-5.62 (m, 1H), 6.96 (d, J=6.8Hz, 2H),
7.10-7.20 (m, 5H), 7.43 (d, J=0.8Hz, 1H), 7.51 (t, J=8.0Hz, 1H), 7.75 (d, J=8.0Hz, 1H),
8.12(s,1H),13.11(br s,1H).13C NMR(150MHz,DMSO-d6)δ:32.2,33.7,54.3,56.6,110.9,
119.4,121.1,123.9,126.4,128.4,128.8,129.5,131.65,131.69,132.2,133.5,140.8,
144.0,157.8,167.4.HRMS calcd for C22H19N2O3:359.1401[M-H]-,found:359.1401。
Embodiment 27
Sequentially added into the pressure pipe of 15mL 1k (48.6mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3k
(65.8mg, 63%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.77-1.92(m,2H),
2.18-2.23 (m, 1H), 2.42-2.47 (m, 1H), 5.64-5.67 (m, 1H), 6.97 (d, J=7.8Hz, 2H), 7.12 (t, J
=7.2Hz, 1H), 7.18-7.20 (m, 3H), 7.35 (t, J=9.6Hz, 1H), 7.49 (s, 1H), 7.57-7.60 (m, 1H),
7.93 (s, 1H), 7.99 (d, J=8.4Hz, 1H), 13.38 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:32.1,
34.2,54.6,115.2(d,2JC-F=22.7Hz), 118.7 (d,2JC-F=14.3Hz), 124.5,124.8 (d,4JC-F=
3.3Hz),126.5,128.4,128.8,129.9,130.2(d,3JC-F=9.3Hz), 132.17 (d,3JC-F=9.6Hz),
132.20,134.9,140.7,143.3(d,4JC-F=2.1Hz), 160.5 (d,1JC-F=248.7Hz), 166.9.19F NMR
(565MHz,DMSO-d6)δ:-113.75.HRMS calcd for C21H16FN2O2:347.1201[M-H]-,found:
347.1200。
Embodiment 28
Sequentially added into the pressure pipe of 15mL 1l (63.7mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3l
(35.9mg, 30%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.74-1.92(m,2H),
2.19-2.26 (m, 1H), 2.41-2.46 (m, 1H), 5.63-5.67 (m, 1H), 6.96 (d, J=7.2Hz, 2H), 7.11 (t, J
=7.2Hz, 1H), 7.16-7.20 (m, 3H), 7.52 (s, 1H), 7.79 (d, J=8.0Hz, 1H), 7.85-7.89 (m, 2H),
8.35(s,1H),13.38(br s,1H).13C NMR(150MHz,DMSO-d6)δ:32.1,34.8,54.9,124.3(q,1JC-F
=270.5Hz), 124.8,125.0 (q,3JC-F=3.6Hz), 125.1 (q,3JC-F=2.9Hz), 126.4,128.4,128.8,
130.0(q,2JC-F=32.1Hz), 130.2,131.0,133.87,133.91,136.0,137.8,140.6,143.1,
167.1.19F NMR(565MHz,DMSO-d6)δ:-61.63.HRMS calcd for C22H16F3N2O2:397.1169[M-H]-,
found:397.1168。
Embodiment 29
Sequentially added into the pressure pipe of 15mL 1m (48.6mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3m
(63.8mg, 61%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.77-1.85(m,2H),
2.24-2.28 (m, 1H), 2.41-2.46 (m, 1H), 5.58-5.61 (m, 1H), 6.96 (d, J=7.8Hz, 2H), 7.12 (t, J
=7.2Hz, 1H), 7.18-7.21 (m, 3H), 7.39-7.43 (m, 2H), 7.47-7.51 (m, 2H), 7.83 (s, 1H), 13.26
(br s,1H).13C NMR(150MHz,DMSO-d6)δ:32.2,33.4,54.3,118.1(d,2JC-F=22.8Hz), 118.8
(d,3JC-F=11.6Hz), 123.3,126.5,128.0,128.36,128.39,128.4,128.9,129.7 (d,3JC-F=
7.8Hz),130.2,133.6,135.7,138.1(d,4JC-F=5.3Hz), 138.4 (d,2JC-F=14.9Hz), 140.7,
159.7(d,1JC-F=251.1Hz), 166.9.19F NMR(376MHz,DMSO-d6)δ:-110.76.HRMS calcd for
C21H16FN2O2:347.1201[M-H]-,found:347.1206。
Embodiment 30
Sequentially added into the pressure pipe of 15mL 1n (43.5mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3n
(41.8mg, 42%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.72-1.79(m,1H),
1.84-1.90 (m, 1H), 2.14-2.18 (m, 1H), 2.41-2.46 (m, 1H), 5.66-5.69 (m, 1H), 6.97 (d, J=
7.8Hz, 2H), 7.12 (t, J=7.8Hz, 1H), 7.19 (t, J=7.2Hz, 2H), 7.27 (s, 1H), 7.60 (s, 1H), 7.90
(s, 1H), 8.01 (d, J=5.4Hz, 1H), 8.62 (d, J=4.8Hz, 1H), 8.82 (s, 1H), 13.31 (br s, 1H)13C
NMR(150MHz,DMSO-d6)δ:32.1,35.3,55.2,121.3,125.3,125.7,126.5,128.4,128.8,
130.8,134.8,136.4,136.6,140.6,142.2,150.5,153.7,167.0.HRMS calcd for
C20H16N3O2:330.1248[M-H]-,found:330.1241。
Embodiment 31
Sequentially added into the pressure pipe of 15mL 1o (47.5mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3o
(67.2mg, 65%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.73-1.81(m,2H),
2.18-2.25 (m, 4H), 2.40-2.47 (m, 1H), 5.48-5.52 (m, 1H), 6.95 (d, J=7.2Hz, 2H), 7.11 (t, J
=7.2Hz, 1H), 7.16-7.20 (m, 3H), 7.44-7.53 (m, 2H), 7.61 (d, J=7.2Hz, 1H), 7.82 (s, 1H),
8.06 (d, J=6.8Hz, 1H), 13.12 (br s, 1H)13C NMR(100MHz,DMSO-d6)δ:13.8,32.2,34.4,
54.6,120.8,126.4,128.4,128.7,128.8,129.0,129.9,130.3,130.5,132.8,133.2,137.4,
139.5,140.8,143.1,167.2.HRMS calcd for C22H19N2O2:343.1452[M-H]-,found:
343.1447。
Embodiment 32
Sequentially added into the pressure pipe of 15mL 1p (66.1mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3p
(85.4mg, 70%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.82-1.91(m,2H),
2.24-2.31(m,1H),2.45-2.49(m,1H),5.62-5.66(m,1H),6.96-6.98(m,2H),7.09-7.13(m,
1H), 7.16-7.20 (m, 2H), 7.25 (t, J=7.2Hz, 1H), 7.41 (t, J=7.6Hz, 2H), 7.50 (td, J1=
7.6Hz,J2=1.2Hz, 1H), 7.57 (td, J1=7.6Hz, J2=1.2Hz, 1H), 7.65 (d, J=7.2Hz, 1H), 7.86-
7.89(m,3H),7.95(s,1H),8.24(dd,J1=7.6Hz, J2=0.8Hz, 1H), 13.21 (br s, 1H)13C NMR
(150MHz,DMSO-d6)δ:32.3,34.4,55.0,120.4,124.9,126.5,127.1,128.4,128.8,129.03,
129.06,129.1,130.3,130.4,130.7,132.8,133.1,134.6,139.7,140.7,141.3,144.5,
167.3.HRMS calcd for C27H21N2O2:405.1609[M-H]-,found:405.1600。
Embodiment 33
Sequentially added into the pressure pipe of 15mL 1q (70.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3q
(90.8mg, 72%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.81-1.90(m,2H),
2.23-2.36(m,4H),2.44-2.48(m,1H),5.59-5.63(m,1H),6.96-6.98(m,2H),7.09-7.12(m,
1H),7.16-7.22(m,4H),7.49(td,J1=7.2Hz, J2=1.2Hz, 1H), 7.56 (td, J1=7.6Hz, J2=
1.6Hz, 1H), 7.63 (d, J=7.2Hz, 1H), 7.74 (d, J=8.4Hz, 2H), 7.87 (s, 1H), 7.88 (s, 1H), 8.22
(dd,J1=7.6Hz, J2=1.2Hz, 1H), 13.17 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:21.3,32.3,
34.4,54.9,119.9,124.9,126.5,128.4,128.8,129.0,129.1,129.6,130.3,130.4,130.6,
131.8,132.8,133.1,136.2,139.7,140.7,141.4,144.3,167.3.HRMS calcd for
C28H23N2O2:419.1765[M-H]-,found:419.1774。
Embodiment 34
Sequentially added into the pressure pipe of 15mL 1r (82.9mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3r
(101.3mg, 73%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.30(s,9H),1.81-
1.89 (m, 2H), 2.24-2.29 (m, 1H), 2.45-2.49 (m, 1H), 5.60-5.63 (m, 1H), 6.97 (d, J=7.2Hz,
2H), 7.11 (t, J=6.6Hz, 1H), 7.18 (t, J=7.2Hz, 2H), 7.42 (d, J=8.4Hz, 2H), 7.49 (t, J=
7.2Hz, 1H), 7.56 (t, J=7.8Hz, 1H), 7.63 (d, J=7.8Hz, 1H), 7.77 (d, J=8.4Hz, 2H), 7.87 (s,
1H), 7.88 (s, 1H), 8.23 (d, J=7.8Hz, 1H), 13.17 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:
31.7,32.2,34.4,34.7,54.9,120.0,124.7,125.8,126.5,128.4,128.8,129.0,129.1,
130.3,130.4,130.6,131.8,132.8,133.1,139.7,140.7,141.4,144.4,149.5,167.3.HRMS
calcd for C31H29N2O2:461.2235[M-H]-,found:461.2239。
Embodiment 35
Sequentially added into the pressure pipe of 15mL 1s (71.5mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3s
(82.8mg, 65%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.84-1.91(m,2H),
2.26-2.33 (m, 1H), 2.46-2.52 (m, 1H), 5.64-5.68 (m, 1H), 6.97 (d, J=6.8Hz, 2H), 7.10-7.13
(m, 1H), 7.18 (t, J=6.8Hz, 2H), 7.26 (t, J=8.8Hz, 2H), 7.51 (td, J1=7.6Hz, J2=1.2Hz,
1H),7.58(td,J1=7.2Hz, J2=1.2Hz, 1H), 7.66 (d, J=7.6Hz, 1H), 7.90-7.95 (m, 4H), 8.26
(d, J=7.6Hz, 1H), 13.21 (br s, 1H)13C NMR(100MHz,DMSO-d6)δ:32.3,34.3,55.0,115.9
(d,2JC-F=20.6Hz), 120.1,126.4,126.8 (d,3JC-F=8.1Hz), 128.4,128.8,129.0,129.1,
130.2,130.4,130.7,131.1(d,4JC-F=2.7Hz), 132.8,133.1,139.7,140.4,140.7,144.6,
161.7(d,1JC-F=242.1Hz), 167.3.19F NMR(376MHz,DMSO-d6)δ:-115.85.HRMS calcd for
C27H20FN2O2:423.1514[M-H]-,found:423.1520。
Embodiment 36
Sequentially added into the pressure pipe of 15mL 1t (76.4mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3t
(97.9mg, 74%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.80-1.91(m,2H),
2.24-2.31(m,1H),2.45-2.49(m,1H),5.61-5.65(m,1H),6.96-6.98(m,2H),7.09-7.12(m,
1H),7.16-7.19(m,2H),7.45-7.47(m,2H),7.50(td,J1=7.2Hz, J2=1.6Hz, 1H), 7.57 (td, J1
=7.6Hz, J2=1.2Hz, 1H), 7.65 (d, J=7.2Hz, 1H), 7.85-7.88 (m, 3H), 8.00 (s, 1H), 8.22 (dd,
J1=8.0Hz, J2=1.2Hz, 1H), 13.21 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:32.3,34.3,55.1,
120.8,126.4,126.6,128.4,128.8,129.0,129.1,129.2,130.1,130.4,130.7,131.4,
132.8,133.1,133.5,139.7,140.1,140.7,144.7,167.2.HRMS calcd for C27H20ClN2O2:
439.1219[M-H]-,found:439.1227。
Embodiment 37
Sequentially added into the pressure pipe of 15mL 1u (89.7mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3u
(104.8mg, 72%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.82-1.91(m,2H),
2.24-2.32 (m, 1H), 2.45-2.49 (m, 1H), 5.62-5.66 (m, 1H), 6.97 (d, J=7.2Hz, 2H), 7.11 (t, J
=7.2Hz, 1H), 7.17 (t, J=6.8Hz, 2H), 7.51 (t, J=7.2Hz, 1H), 7.55-7.61 (m, 3H), 7.65 (d, J
=7.2Hz, 1H), 7.82 (d, J=8.4Hz, 2H), 7.89 (s, 1H), 8.01 (s, 1H), 8.23 (d, J=7.6Hz, 1H),
13.26(br s,1H).13C NMR(100MHz,DMSO-d6)δ:32.3,34.3,55.1,119.9,120.8,126.4,
126.9,128.4,128.8,129.1,129.2,130.1,130.4,130.7,132.0,132.8,133.2,133.8,
139.6,140.1,140.7,144.7,167.3.HRMS calcd for C27H20BrN2O2:483.0714[M-H]-,found:
483.0723。
Embodiment 38
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2b (63.1mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3v
(55.9mg, 66%).The characterize data of the compound is as follows:1HNMR(600MHz,DMSO-d6) δ: 0.69 (t, J=7.2Hz,
3H), 0.86-0.91 (m, 1H), 1.03-1.15 (m, 3H), 1.46-1.52 (m, 2H), 5.50 (t, J=8.4Hz, 1H), 7.11
(s, 1H), 7.44-7.46 (m, 2H), 7.51 (t, J=7.2Hz, 1H), 7.60 (d, J=7.2Hz, 1H), 7.82 (s, 1H),
8.12 (d, J=7.8Hz, 1H), 13.14 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:14.1,21.8,28.3,
32.5,54.9,124.1,128.76,128.82,128.9,129.4,129.5,130.3,130.4,130.6,132.70,
132.74,133.5,139.4,139.5,144.2,167.4.HRMS calcd for C17H17N2O2:281.1296[M-H]-,
found:281.1301。
Embodiment 39
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2c (69.4mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3w
(60.5mg, 68%).The characterize data of the compound is as follows:1HNMR(400MHz,DMSO-d6) δ: 0.73 (t, J=6.8Hz,
3H), 0.90-0.95 (m, 1H), 1.00-1.09 (m, 5H), 1.46-1.51 (m, 2H), 5.51 (t, J=7.6Hz, 1H), 7.11
(d, J=0.4Hz, 1H), 7.44-7.53 (m, 3H), 7.59-7.61 (m, 1H), 7.82 (s, 1H), 8.11-8.13 (m, 1H),
13.15(br s,1H).13C NMR(150MHz,DMSO-d6)δ:14.1,22.2,25.6,30.7,32.7,54.9,124.06,
124.10,128.7,128.8,128.9,129.4,129.5,130.3,130.4,130.6,132.7,133.5,139.4,
139.5,144.2,167.3.HRMS calcd for C18H19N2O2:295.1452[M-H]-,found:295.1452。
Embodiment 40
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2d (75.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3x
(62.4mg, 67%).The characterize data of the compound is as follows:1HNMR(600MHz,DMSO-d6) δ: 0.76 (t, J=7.2Hz,
3H), 0.89-0.91 (m, 1H), 1.04-1.14 (m, 7H), 1.46-1.50 (m, 2H), 5.50 (t, J=7.8Hz, 1H), 7.11
(s, 1H), 7.44-7.47 (m, 2H), 7.51 (t, J=7.2Hz, 1H), 7.60 (d, J=7.2Hz, 1H), 7.81 (s, 1H),
8.11 (d, J=7.8Hz, 1H), 13.15 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:14.3,22.2,25.9,
28.2,31.4,32.7,54.9,124.0,128.78,128.84,129.4,130.2,130.5,130.6,132.7,133.6,
139.4,144.2,167.4.HRMS calcd for C19H21N2O2:309.1609[M-H]-,found:309.1600。
Embodiment 41
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2e (88.3mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3y
(67.0mg, 66%).The characterize data of the compound is as follows:1HNMR(400MHz,DMSO-d6) δ: 0.81 (t, J=6.8Hz,
3H), 0.90-0.91 (m, 1H), 1.06-1.20 (m, 11H), 1.46-1.49 (m, 2H), 5.50 (t, J=7.6Hz, 1H), 7.11
(s, 1H), 7.44-7.53 (m, 3H), 7.60 (d, J=7.2Hz, 1H), 7.81 (s, 1H), 8.12 (d, J=7.6Hz, 1H),
13.15(br s,1H).13C NMR(150MHz,DMSO-d6)δ:14.4,22.5,25.9,28.5,28.8,29.0,31.6,
32.7,54.9,124.1,128.8,129.4,129.5,130.3,130.4,130.6,132.7,133.5,139.4,139.5,
144.2,167.3.HRMS calcd for C21H25N2O2:337.1922[M-H]-,found:337.1922。
Embodiment 42
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2f (107.3mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 3z
(74.2mg, 65%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:0.82-0.91(m,4H),
1.05-1.25 (m, 17H), 1.45-1.49 (m, 2H), 5.50 (t, J=7.6Hz, 1H), 7.10 (s, 1H), 7.43-7.52 (m,
3H), 7.59 (d, J=7.2Hz, 1H), 7.81 (s, 1H), 8.12 (d, J=7.6Hz, 1H), 13.15 (br s, 1H)13C NMR
(150MHz,DMSO-d6)δ:14.4,22.5,25.9,28.5,29.06,29.14,29.4,31.7,32.6,54.9,124.0,
128.7,128.8,129.4,129.5,130.2,130.4,130.6,132.7,133.5,139.4,139.5,144.2,
167.3.HRMS calcd for C24H31N2O2:379.2391[M-H]-,found:379.2391。
Embodiment 43
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2g (109.9mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3aa (71.9mg, 62%).The characterize data of the compound is as follows:1HNMR(600MHz,DMSO-d6) δ: 0.33 (d, J=
6.6Hz, 1.5H), 0.63 (d, J=6.6Hz, 1.5H), 1.09-1.12 (m, 6H), 1.78-1.86 (m, 1H), 1.91-1.93
(m,0.5H),2.03-2.07(m,0.5H),2.13-2.17(m,0.5H),2.60-2.63(m,0.5H),2.71-2.79(m,
1H), 5.33-5.36 (m, 1H), 6.58 (d, J=7.8Hz, 1H), 6.75 (d, J=8.4Hz, 1H), 6.98 (d, J=8.4Hz,
1H), 7.03 (d, J=7.8Hz, 1H), 7.11 (s, 0.5H), 7.15 (s, 0.5H), 7.46-7.52 (m, 2H), 7.55-7.58
(m, 1H), 7.60 (d, J=7.8Hz, 0.5H), 7.67-7.69 (m, 0.5H), 7.88 (s, 0.5H), 7.95 (s, 0.5H),
8.07-8.09 (m, 0.5H), 8.17 (d, J=7.8Hz, 0.5H), 13.19 (br s, 1H)13C NMR(150MHz,DMSO-d6)
δ:15.8,16.1,24.29,24.31,24.34,33.37,33.40,38.3,38.6,38.7,39.2,59.6,59.7,
124.6,124.7,126.6,126.7,128.6,128.7,128.8,128.90,128.93,129.3,129.5,130.3,
130.6,130.68,130.74,130.8,132.3,132.4,133.2,133.4,137.2,137.5,139.3,139.6,
146.4,146.5,167.7,167.8.HRMS calcd for C25H25N2O2:385.1922[M-H]-,found:
385.1922。
Embodiment 44
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2h (68.5mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3bb (58.3mg, 66%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.01-1.05(m,
1H),1.12-1.18(m,1H),1.24-1.43(m,4H),1.52-1.58(m,2H),2.04-2.10(m,1H),5.31(d,J
=10.8Hz, 1H), 7.12 (s, 1H), 7.46 (t, J=7.8Hz, 1H), 7.50-7.53 (m, 2H), 7.62 (d, J=7.2Hz,
1H), 7.88 (s, 1H), 8.13 (d, J=7.2Hz, 1H), 13.20 (br s, 1H)13C NMR(150MHz,DMSO-d6)δ:
24.4,24.9,29.2,30.1,42.9,58.8,124.2,128.78,128.82,129.2,130.3,130.6,130.7,
132.7,133.2,139.5,144.2,167.8.HRMS calcd for C18H17N2O2:293.1296[M-H]-,found:
293.1293。
Embodiment 45
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2i (78.4mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3cc (52.2mg, 55%).The characterize data of the compound is as follows:1HNMR(400MHz,DMSO-d6)δ:2.72(dd,J1=
13.2Hz,J2=9.2Hz, 1H), 2.81 (dd, J1=13.2Hz, J2=6.4Hz, 1H), 5.70-5.74 (m, 1H), 6.82 (dd,
J1=7.6Hz, J2=1.6Hz, 2H), 6.93 (d, J=0.8Hz, 1H), 7.03 (d, J=0.8Hz, 1H), 7.12-7.19 (m,
3H),7.51(td,J1=7.2Hz, J2=1.2Hz, 1H), 7.58 (td, J1=7.6Hz, J2=1.6Hz, 1H), 7.68 (d, J=
7.2Hz,1H),7.88(s,1H),8.20(dd,J1=7.6Hz, J2=1.2Hz, 1H), 13.04 (br s, 1H)13C NMR
(150MHz,DMSO-d6)δ:38.6,56.5,123.8,127.1,128.7,128.9,129.0,129.2,130.47,
130.50,130.9,132.8,136.9,139.7,144.3,167.1.HRMS calcd for C20H15N2O2:315.1139
[M-H]-,found:315.1121。
Embodiment 46
Sequentially added into the pressure pipe of 15mL 1a (43.3mg, 0.3mmol), methylene chloride (3mL), 2j (83.3mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3dd (40.3mg, 41%).The characterize data of the compound is as follows:1HNMR(400MHz,DMSO-d6) δ: 6.90 (d, J=
8.0Hz, 2H), 7.02 (s, 1H), 7.25 (d, J=1.2Hz, 1H), 7.36 (td, J1=7.6Hz, J2=1.6Hz, 1H), 7.43
(td,J1=7.6Hz, J2=1.6Hz, 1H), 7.53 (d, J=6.8Hz, 1H), 7.65 (d, J=8.4Hz, 2H), 7.83 (d, J=
1.2Hz,1H),8.02-8.05(m,2H),13.52(br s,1H).13C NMR(150MHz,DMSO-d6)δ:56.3,110.9,
118.8,124.5,126.8,128.8,129.0,130.2,130.3,130.7,132.1,132.8,132.9,141.5,
144.6,145.1,167.7.HRMS calcd for C20H12N3O2:326.0935[M-H]-,found:326.0930。
Embodiment 47
Sequentially added into the pressure pipe of 15mL 1b (47.5mg, 0.3mmol), methylene chloride (3mL), 2c (69.4mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3ee (56.8mg, 61%).The characterize data of the compound is as follows:1HNMR(400MHz,DMSO-d6) δ: 0.73 (t, J=
6.8Hz,3H),0.88-0.92(m,1H),1.02-1.08(m,5H),1.44-1.48(m,2H),2.37(s,3H),5.47(t,J
=7.6Hz, 1H), 7.07 (s, 1H), 7.33 (d, J=8.0Hz, 1H), 7.40-7.42 (m, 2H), 7.75 (s, 1H), 8.00 (d,
J=8.0Hz, 1H), 13.02 (br s, 1H)13C NMR(150MHz,CF3CO2D)δ:11.8,19.6,21.4,25.1,30.1,
30.5,58.2,118.0,119.8,123.6,128.1,130.5,131.5,132.5,133.8,142.4,142.7,145.8,
169.8.HRMS calcd for C19H21N2O2:309.1609[M-H]-,found:309.1613。
Embodiment 48
Sequentially added into the pressure pipe of 15mL 1b (47.5mg, 0.3mmol), methylene chloride (3mL), 2h (68.5mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3ff (37.0mg, 40%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.01-1.55(m,
8H), 2.06-2.08 (m, 1H), 2.37 (s, 3H), 5.26 (d, J=10.8Hz, 1H), 7.06 (s, 1H), 7.32 (d, J=
7.6Hz, 1H), 7.42 (s, 1H), 7.46 (s, 1H), 7.80 (s, 1H), 8.01 (d, J=8.0Hz, 1H), 13.08 (br s,
1H).13C NMR(150MHz,DMSO-d6)δ:21.0,24.4,24.9,29.2,30.1,42.8,58.7,123.9,128.3,
128.8,129.1,130.5,131.2,132.9,133.0,138.3,139.6,144.3,167.8.HRMS calcd for
C19H19N2O2:307.1452[M-H]-,found:307.1449。
Embodiment 49
Sequentially added into the pressure pipe of 15mL 1e (48.6mg, 0.3mmol), methylene chloride (3mL), 2c (69.4mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3gg (50.0mg, 53%).The characterize data of the compound is as follows:1HNMR(600MHz,DMSO-d6) δ: 0.73 (t, J=
7.2Hz, 3H), 0.90-0.92 (m, 1H), 1.03-1.10 (m, 5H), 1.47-1.50 (m, 2H), 5.50 (t, J=7.8Hz,
1H), 7.10 (s, 1H), 7.36-7.39 (m, 1H), 7.46 (s, 1H), 7.55 (d, J=9.6Hz, 1H), 7.80 (s, 1H),
8.12-8.15(m,1H),13.18(br s,1H).13C NMR(150MHz,DMSO-d6)δ:14.1,22.2,25.6,30.7,
32.7,54.8,117.6(d,2JC-F=21.5Hz), 118.4 (d,2JC-F=22.4Hz), 124.0,127.3,129.5,131.3
(d,3JC-F=9.3Hz), 132.6 (d,3JC-F=6.9Hz), 134.7,138.3,143.6,161.9 (d,1JC-F=245.1Hz),
167.2.19F NMR(376MHz,DMSO-d6)δ:-113.63.HRMS calcd for C18H18FN2O2:313.1358[M-
H]-,found:313.1358。
Embodiment 50
Sequentially added into the pressure pipe of 15mL 1e (48.6mg, 0.3mmol), methylene chloride (3mL), 2h (68.5mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3hh (45.9mg, 49%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:0.99-1.06(m,
1H), 1.11-1.46 (m, 5H), 1.50-1.62 (m, 2H), 2.03-2.10 (m, 1H), 5.30 (d, J=10.8Hz, 1H), 7.10
(d, J=0.8Hz, 1H), 7.37 (td, J1=8.4Hz, J2=2.8Hz, 1H), 7.50 (d, J=0.8Hz, 1H), 7.56 (dd, J1
=10.0Hz, J2=2.4Hz, 1H), 7.85 (s, 1H), 8.13-8.16 (m, 1H), 13.28 (br s, 1H)13C NMR
(100MHz,DMSO-d6)δ:24.4,24.9,29.2,30.1,43.0,58.6,117.6(d,2JC-F=21.4Hz), 118.4 (d
,2JC-F=22.9Hz), 124.1,127.5 (d,4JC-F=2.6Hz), 129.3,131.2 (d,3JC-F=8.4Hz), 132.7 (d,3JC-F=9.2Hz), 134.4,138.3,143.6,161.9 (d,1JC-F=243.4Hz), 167.6.19F NMR(376MHz,
DMSO-d6)δ:-113.66.HRMS calcd for C18H16FN2O2:311.1201[M-H]-,found:311.1201。
Embodiment 51
Sequentially added into the pressure pipe of 15mL 1p (66.1mg, 0.3mmol), methylene chloride (3mL), 2c (69.4mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3ii (82.7mg, 74%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6) δ: 0.72 (t, J=
6.4Hz, 3H), 1.01-1.18 (m, 6H), 1.54-1.57 (m, 2H), 5.61 (t, J=7.2Hz, 1H), 7.25 (t, J=
7.2Hz, 1H), 7.41 (t, J=7.2Hz, 2H), 7.50 (t, J=7.2Hz, 1H), 7.58 (t, J=7.2Hz, 1H), 7.65 (d,
J=7.6Hz, 1H), 7.89-7.92 (m, 3H), 7.98 (s, 1H), 8.30 (d, J=7.6Hz, 1H), 13.23 (br s, 1H)13C
NMR(150MHz,DMSO-d6)δ:14.1,22.2,25.7,30.8,32.6,55.3,120.4,124.9,127.0,129.0,
130.3,130.4,130.7,132.8,133.3,134.6,139.5,141.2,144.5,167.4.HRMS calcd for
C24H23N2O2:371.1765[M-H]-,found:371.1765。
Embodiment 52
Sequentially added into the pressure pipe of 15mL 1p (66.1mg, 0.3mmol), methylene chloride (3mL), 2h (68.5mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product
3jj (62.2mg, 56%).The characterize data of the compound is as follows:1H NMR(400MHz,DMSO-d6)δ:1.09-1.15(m,
1H), 1.18-1.45 (m, 5H), 1.54-1.58 (m, 2H), 2.09-2.16 (m, 1H), 5.33 (d, J=11.2Hz, 1H), 7.23
(t, J=7.2Hz, 1H), 7.39 (t, J=7.6Hz, 2H), 7.47-7.51 (m, 1H), 7.54-7.58 (m, 1H), 7.65 (d, J
=7.2Hz, 1H), 7.84 (d, J=7.6Hz, 2H), 7.91 (s, 1H), 8.03 (s, 1H), 8.23 (d, J=7.2Hz, 1H),
13.18(br s,1H).13C NMR(150MHz,DMSO-d6)δ:24.4,24.9,29.3,30.2,59.1,120.6,124.8,
127.0,128.98,129.02,130.4,130.5,130.8,132.8,133.0,134.6,139.5,141.1,144.5,
167.8.HRMS calcd for C24H21N2O2:369.1609[M-H]-,found:369.1608。
Embodiment 53
Sequentially added into the pressure pipe of 15mL 4a (58.3mg, 0.3mmol), methylene chloride (3mL), 2a (84.7mg,
0.45mmol), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer (4.7mg, 0.0075mmol) and silver acetate
Then pressure pipe is sealed and placed in 100 DEG C of oil baths and reacts 10h by (100.1mg, 0.6mmol).To after reaction, cool down
It to room temperature, filters, is spin-dried for, cross silica gel post separation (methylene chloride/methanol/acetic acid=30/1/0.1) and obtain white solid product 5a
(62.8mg, 55%).The characterize data of the compound is as follows:1H NMR(600MHz,DMSO-d6)δ:1.76-1.80(m,2H),
2.26-2.31 (m, 1H), 2.42-2.47 (m, 1H), 5.69 (t, J=7.8Hz, 1H), 6.84 (d, J=7.8Hz, 2H), 7.04-
7.10 (m, 3H), 7.30 (s, 1H), 7.47 (s, 1H), 7.59-7.64 (m, 2H), 7.67 (d, J=8.4Hz, 1H), 7.94 (s,
1H), 7.97-7.99 (m, 2H), 8.99 (d, J=8.4Hz, 1H), 13.17 (br s, 1H)13C NMR(150MHz,DMSO-d6)
δ:32.0,32.3,54.8,122.9,126.4,127.4,127.8,128.0,128.3,128.35,128.38,128.4,
128.5,128.8,129.0,129.1,129.3,129.4,129.6,129.7,131.3,134.1,135.8,139.5,
139.6,140.8,142.1,166.9.HRMS calcd for C25H19N2O2:379.1452[M-H]-,found:
379.1450。
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (4)
1. a kind of synthetic method of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound, feature exist
In specific synthesis process are as follows: by 2- Aryimidazole or 2- heteroaryl-imidazole azole compounds 1 and 2- methene propiolactone class compound 2
It is dissolved in solvent, catalyst and oxidant is then added, reacted in 80-120 DEG C and 5H- benzo [c] imidazo [1,2-a] nitrogen is made
Heterocycle heptene -6- carboxylic acid compound 3, the reaction equation in the synthetic method are as follows:
Wherein R1For hydrogen, fluorine, chlorine, bromine, trifluoromethyl, C1-4Alkyl or C1-4Alkoxy, R2For hydrogen, C1-4Alkyl, C1-4Alkoxy,
Phenyl or substituted-phenyl, R3For C1-16Alkyl replaces alkyl, phenyl or substituted-phenyl, replace alkyl substituent group be phenyl or
Substituted-phenyl, the substituent group on the substituted-phenyl phenyl ring is fluorine, chlorine, bromine, C1-4Alkyl, C1-4Alkoxy or cyano, X C
Or N, catalyst are that dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer, bis- (the 4- isopropyl methyl phenyl) rutheniums of dichloro
(II), dichloro (pentamethylcyclopentadiene base) closes iridium (III) dimer or pentamethylcyclopentadiene base rhodium acetate (III), oxidation
Agent be silver acetate or silver carbonate, solvent 1,2- dichloroethanes, methanol, hexafluoroisopropanol, toluene, acetonitrile, methylene chloride or 1,
4- dioxane.
2. the conjunction of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound according to claim 1
At method, it is characterised in that: the 2- Aryimidazole or 2- heteroaryl-imidazole azole compounds 1,2- methene propiolactone class
Closing the ratio between amount for the substance that feeds intake of object 2, catalyst and oxidant is 1:1-2:0.025:1-2.
3. a kind of synthetic method of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound, feature exist
In specific synthesis process are as follows: 2- aryl imidazoles 4 and 2- methene propiolactone class compound 2 are dissolved in solvent, so
Catalyst and oxidant are added afterwards, is reacted in 80-120 DEG C and 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic is made
Acid compounds 5, the reaction equation in the synthetic method are as follows:
Wherein R2For hydrogen, C1-4Alkyl, C1-4Alkoxy, phenyl or substituted-phenyl, R3For C1-16Alkyl or replace alkyl, phenyl or
Substituted-phenyl, replacing the substituent group of alkyl is phenyl or substituted-phenyl, the substituent group on the substituted-phenyl phenyl ring be fluorine,
Chlorine, bromine, C1-4Alkyl, C1-4Alkoxy or cyano, catalyst be dichloro (pentamethylcyclopentadiene base) close rhodium (III) dimer,
Bis- (the 4- isopropyl methyl phenyl) rutheniums (II) of dichloro, dichloro (pentamethylcyclopentadiene base) close iridium (III) dimer or pentamethyl
Cyclopentadienyl group rhodium acetate (III), oxidant are silver acetate or silver carbonate, solvent 1,2- dichloroethanes, methanol, hexafluoro isopropyl
Alcohol, toluene, acetonitrile, methylene chloride or 1,4- dioxane.
4. the conjunction of 5H- benzo [c] imidazo [1,2-a] azepine -6- carboxylic acid compound according to claim 3
At method, it is characterised in that: the 2- aryl imidazoles 4,2- methene propiolactone class compound 2, catalyst and
The ratio between amount for the substance that feeds intake of oxidant is 1:1-2:0.025:1-2.
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| CN110746319A (en) * | 2019-11-13 | 2020-02-04 | 河南师范大学 | Synthesis method of E-type benzofulvene derivative |
| CN111138430A (en) * | 2020-02-10 | 2020-05-12 | 河南师范大学 | Method for synthesizing imidazole-containing fused heterocyclic compound |
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| CN110746319A (en) * | 2019-11-13 | 2020-02-04 | 河南师范大学 | Synthesis method of E-type benzofulvene derivative |
| CN110746319B (en) * | 2019-11-13 | 2022-03-01 | 河南师范大学 | Synthesis method of E-type benzofulvene derivative |
| CN111138430A (en) * | 2020-02-10 | 2020-05-12 | 河南师范大学 | Method for synthesizing imidazole-containing fused heterocyclic compound |
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