CN105384674A - 一种二苯基取代吲哚化合物的合成方法 - Google Patents
一种二苯基取代吲哚化合物的合成方法 Download PDFInfo
- Publication number
- CN105384674A CN105384674A CN201510740386.4A CN201510740386A CN105384674A CN 105384674 A CN105384674 A CN 105384674A CN 201510740386 A CN201510740386 A CN 201510740386A CN 105384674 A CN105384674 A CN 105384674A
- Authority
- CN
- China
- Prior art keywords
- compound
- synthetic method
- formula
- following formula
- mol ratio
- 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
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 14
- -1 indole compound Chemical class 0.000 title claims abstract description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims abstract description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 235000010290 biphenyl Nutrition 0.000 title abstract description 3
- 125000006267 biphenyl group Chemical group 0.000 title abstract description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title abstract description 3
- 230000002194 synthesizing effect Effects 0.000 title abstract description 3
- 239000004305 biphenyl Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 239000003446 ligand Substances 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 4
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 40
- 238000010189 synthetic method Methods 0.000 claims description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 18
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 12
- 239000010949 copper Substances 0.000 claims description 12
- 150000002941 palladium compounds Chemical class 0.000 claims description 8
- JNGRYGYMVRKYBE-UHFFFAOYSA-N copper;2,2,2-trifluoroacetic acid Chemical compound [Cu].OC(=O)C(F)(F)F JNGRYGYMVRKYBE-UHFFFAOYSA-N 0.000 claims description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
- SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- DWOZNANUEDYIOF-UHFFFAOYSA-L bis(di-tert-butyl(4-dimethylaminophenyl)-phosphine)dichloropalladium(II) Substances Cl[Pd]Cl.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 DWOZNANUEDYIOF-UHFFFAOYSA-L 0.000 description 11
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- IQTHEAQKKVAXGV-UHFFFAOYSA-N 4-ditert-butylphosphanyl-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 IQTHEAQKKVAXGV-UHFFFAOYSA-N 0.000 description 5
- 229960004926 chlorobutanol Drugs 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 101150003085 Pdcl gene Proteins 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 150000002475 indoles Chemical group 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- OZIPZJIDBQUAJM-UHFFFAOYSA-N CC(C)(C)P(C(C)(C)C)C(C=C1)=CC=C1N(C)C.Cl.Cl Chemical compound CC(C)(C)P(C(C)(C)C)C(C=C1)=CC=C1N(C)C.Cl.Cl OZIPZJIDBQUAJM-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510740386.4A CN105384674B (zh) | 2015-11-04 | 2015-11-04 | 一种二苯基取代吲哚化合物的合成方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510740386.4A CN105384674B (zh) | 2015-11-04 | 2015-11-04 | 一种二苯基取代吲哚化合物的合成方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105384674A true CN105384674A (zh) | 2016-03-09 |
CN105384674B CN105384674B (zh) | 2017-08-25 |
Family
ID=55417502
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510740386.4A Expired - Fee Related CN105384674B (zh) | 2015-11-04 | 2015-11-04 | 一种二苯基取代吲哚化合物的合成方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105384674B (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008093637A1 (ja) * | 2007-01-29 | 2008-08-07 | Wako Pure Chemical Industries, Ltd. | 有機トリオールボレート塩を含んでなる有機合成反応用試薬 |
CN103420860A (zh) * | 2013-07-24 | 2013-12-04 | 温州大学 | 一种氨基取代芳酯化合物的合成方法 |
CN104193628A (zh) * | 2014-08-12 | 2014-12-10 | 庄伟萍 | 一种用作医药中间体的氨基芳酮化合物及其合成方法 |
CN104591938A (zh) * | 2015-01-29 | 2015-05-06 | 杨海霞 | 一种医药中间体二芳基甲烷类化合物的合成方法 |
-
2015
- 2015-11-04 CN CN201510740386.4A patent/CN105384674B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008093637A1 (ja) * | 2007-01-29 | 2008-08-07 | Wako Pure Chemical Industries, Ltd. | 有機トリオールボレート塩を含んでなる有機合成反応用試薬 |
CN103420860A (zh) * | 2013-07-24 | 2013-12-04 | 温州大学 | 一种氨基取代芳酯化合物的合成方法 |
CN104193628A (zh) * | 2014-08-12 | 2014-12-10 | 庄伟萍 | 一种用作医药中间体的氨基芳酮化合物及其合成方法 |
CN104591938A (zh) * | 2015-01-29 | 2015-05-06 | 杨海霞 | 一种医药中间体二芳基甲烷类化合物的合成方法 |
Non-Patent Citations (9)
Also Published As
Publication number | Publication date |
---|---|
CN105384674B (zh) | 2017-08-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102746210A (zh) | 一种西洛多辛关键中间体的合成方法 | |
CN105198841A (zh) | 一种药物中间体多取代呋喃类化合物的合成方法 | |
CN105949118A (zh) | 一种2-芳基喹啉衍生物的制备方法 | |
CN103408525B (zh) | 一种黄酮类化合物的合成方法及其应用 | |
CN105237372A (zh) | 一种药物中间体芳基酮类化合物的催化合成方法 | |
CN105085458B (zh) | 一种香豆素类衍生物的合成方法 | |
WO2016141842A1 (zh) | 磷酸钾环境下合成医药中间体菲化合物的方法 | |
CN105384674A (zh) | 一种二苯基取代吲哚化合物的合成方法 | |
CN105085272A (zh) | 一种芳基或杂芳基酯类化合物的合成方法 | |
CN104803912B (zh) | 一种医药中间体喹啉化合物的合成方法 | |
CN101531578B (zh) | 一种制备光学活性的轴手性联芳香类化合物的方法 | |
CN104086342B (zh) | 一种医药中间体芳基取代甲醇化合物的合成方法 | |
CN105198867A (zh) | 一种苯并噻唑衍生物的催化合成方法 | |
CN106278839A (zh) | 一种医药中间体二芳基酮类化合物的合成方法 | |
CN105085307A (zh) | 一种酰胺类化合物的合成方法 | |
CN105218553A (zh) | 一种药物中间体吡咯并吲哚类化合物的合成方法 | |
CN105367512A (zh) | 一种药物中间体苯并噻唑类化合物的合成方法 | |
CN105384677A (zh) | 一种医药中间体芳基取代吲哚类化合物的合成方法 | |
CN104788273B (zh) | 一种医药中间体酮酯类化合物的合成方法 | |
CN104529879A (zh) | 一种2-取代吡啶类药物中间体化合物的合成方法 | |
CN105294518A (zh) | 一种医药中间体芳基磺酰化合物的合成方法 | |
CN105130952A (zh) | 一种医药中间体醛基取代噻吩化合物的合成方法 | |
CN104961727A (zh) | 一种吡咯类衍生物的新型合成方法 | |
CN105503771A (zh) | 一种医药中间体稠环噻唑类化合物的合成方法 | |
CN105218424A (zh) | 一种吡咯类化合物的催化合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Liu Yanfang Inventor before: Zhang Yan |
|
TA01 | Transfer of patent application right |
Effective date of registration: 20170718 Address after: 330114 village of Jiangxi Province, Xinjian County Lehua town bear natural Village No. 10 Applicant after: Liu Yanfang Address before: Room 61, No. 2, South Village, Xuhui District, Shanghai, 200237, China Applicant before: Zhang Yan |
|
TA01 | Transfer of patent application right | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Ma Jun Inventor after: Liu Xingwei Inventor after: Jiang Anxue Inventor before: Liu Yanfang |
|
TA01 | Transfer of patent application right | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170727 Address after: 730900 Baiyin, Baiyin District, Lan Bao Road, No. 333 (08) 1-01 incubator base, building, room two, building 411, room 3 Applicant after: Gansu Haojun Pharmaceutical Co.,Ltd. Address before: 330114 village of Jiangxi Province, Xinjian County Lehua town bear natural Village No. 10 Applicant before: Liu Yanfang |
|
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170825 Termination date: 20211104 |
|
CF01 | Termination of patent right due to non-payment of annual fee |