CN105111125A - 一种药物中间体稠杂环酮类化合物的合成方法 - Google Patents
一种药物中间体稠杂环酮类化合物的合成方法 Download PDFInfo
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- CN105111125A CN105111125A CN201510634218.7A CN201510634218A CN105111125A CN 105111125 A CN105111125 A CN 105111125A CN 201510634218 A CN201510634218 A CN 201510634218A CN 105111125 A CN105111125 A CN 105111125A
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- 239000003814 drug Substances 0.000 title abstract description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract 2
- 238000001308 synthesis method Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 48
- 238000010189 synthetic method Methods 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000012752 auxiliary agent Substances 0.000 claims description 19
- -1 heterocycle ketone compounds Chemical class 0.000 claims description 17
- 239000003513 alkali Substances 0.000 claims description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical group COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 15
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 14
- 239000000377 silicon dioxide Substances 0.000 claims description 14
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 150000004032 porphyrins Chemical class 0.000 claims description 12
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 150000001282 organosilanes Chemical class 0.000 claims description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FJWRGPWPIXAPBJ-UHFFFAOYSA-N diethyl(dimethyl)silane Chemical compound CC[Si](C)(C)CC FJWRGPWPIXAPBJ-UHFFFAOYSA-N 0.000 claims description 3
- YYLGKUPAFFKGRQ-UHFFFAOYSA-N dimethyldiethoxysilane Chemical compound CCO[Si](C)(C)OCC YYLGKUPAFFKGRQ-UHFFFAOYSA-N 0.000 claims description 3
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 2
- 235000015320 potassium carbonate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 6
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 230000009467 reduction Effects 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000012450 pharmaceutical intermediate 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
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 0 *[C@](C1)C(*)(C2)ON1C2(*)I Chemical compound *[C@](C1)C(*)(C2)ON1C2(*)I 0.000 description 1
- SBEVOFOYIKNKQL-UHFFFAOYSA-N CC(C1)(NCCC1=O)I Chemical compound CC(C1)(NCCC1=O)I SBEVOFOYIKNKQL-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000010504 bond cleavage reaction Methods 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
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 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
- 230000006872 improvement Effects 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims (10)
Priority Applications (2)
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CN201710661934.3A CN107353240A (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
CN201510634218.7A CN105111125B (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
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CN201510634218.7A CN105111125B (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
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CN201710661934.3A Division CN107353240A (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
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CN105111125A true CN105111125A (zh) | 2015-12-02 |
CN105111125B CN105111125B (zh) | 2017-09-22 |
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CN201510634218.7A Active CN105111125B (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
CN201710661934.3A Withdrawn CN107353240A (zh) | 2015-09-30 | 2015-09-30 | 一种药物中间体稠杂环酮类化合物的合成方法 |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104496884A (zh) * | 2014-12-09 | 2015-04-08 | 大连理工大学 | 一种3-氧代吲哚啉类化合物的制备方法 |
-
2015
- 2015-09-30 CN CN201510634218.7A patent/CN105111125B/zh active Active
- 2015-09-30 CN CN201710661934.3A patent/CN107353240A/zh not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104496884A (zh) * | 2014-12-09 | 2015-04-08 | 大连理工大学 | 一种3-氧代吲哚啉类化合物的制备方法 |
Non-Patent Citations (2)
Title |
---|
CHEPURI V. SUNEEL KUMAR等: "InCl3-mediated addition of indole to isatogens: an expeditious synthesis of 13-deoxy-isatisine A", 《CHEM. EUR. J.》 * |
CHEPURI V. SUNEEL KUMAR等: "Ru-catalyzed redox-neutral cleavage of the N-O bond in isoxazolidines: isatogens to pseudoxindoxyls via a one-pot [3 + 2]-cycloaddition/N-O cleavage", 《ORGANIC LETTERS》 * |
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Publication number | Publication date |
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CN105111125B (zh) | 2017-09-22 |
CN107353240A (zh) | 2017-11-17 |
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CB03 | Change of inventor or designer information |
Inventor after: Tan Pingzhong Inventor after: Tan Pingan Inventor after: Zhou Yongheng Inventor after: Ma Fei Inventor after: Chen Jun Inventor before: Zhu Yong |
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CB03 | Change of inventor or designer information | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170808 Address after: 901 No. 12, No. 905, No. 88, South Garden Road, Chengdu hi tech Zone, Sichuan, 610000 Applicant after: CHENGDU ORGANOCHEM CO., LTD. Address before: On the 415905 Changde city of Hunan province Hanshou County Tan Xiang Liu Jia Kawamura Taeko Temple Group Applicant before: Zhu Yong |
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