CN106554333B - 一种药物中间体的合成方法 - Google Patents
一种药物中间体的合成方法 Download PDFInfo
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- CN106554333B CN106554333B CN201510632093.4A CN201510632093A CN106554333B CN 106554333 B CN106554333 B CN 106554333B CN 201510632093 A CN201510632093 A CN 201510632093A CN 106554333 B CN106554333 B CN 106554333B
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- chemical compounds
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- synthetic method
- pharmaceutical intermediate
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- 239000012450 pharmaceutical intermediate Substances 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 239000002994 raw material Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 13
- 239000007800 oxidant agent Substances 0.000 claims abstract description 12
- 230000001590 oxidative effect Effects 0.000 claims abstract description 12
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 96
- 238000006243 chemical reaction Methods 0.000 claims description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 18
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- YAXWOADCWUUUNX-UHFFFAOYSA-N 1,2,2,3-tetramethylpiperidine Chemical compound CC1CCCN(C)C1(C)C YAXWOADCWUUUNX-UHFFFAOYSA-N 0.000 claims description 9
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-Tetramethylpiperidine Substances CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 239000002808 molecular sieve Substances 0.000 claims description 8
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 8
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000012190 activator Substances 0.000 claims description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000012074 organic phase Substances 0.000 description 22
- 239000007788 liquid Substances 0.000 description 14
- 238000000926 separation method Methods 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 230000006837 decompression Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000005708 Sodium hypochlorite Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 description 1
- 0 C*[C@]([C@@](COC(c1ccccc1)=O)O)[C@](C)(CO)F Chemical compound C*[C@]([C@@](COC(c1ccccc1)=O)O)[C@](C)(CO)F 0.000 description 1
- OUKYMZJNLWKCSO-JXXFODFXSA-N C[C@@]([C@@H]([C@@H](COC(c1ccccc1)=O)O1)OC(c2ccccc2)=O)(C1=O)F Chemical compound C[C@@]([C@@H]([C@@H](COC(c1ccccc1)=O)O1)OC(c2ccccc2)=O)(C1=O)F OUKYMZJNLWKCSO-JXXFODFXSA-N 0.000 description 1
- MGQBJSHOIUJIFV-SEFOKTEQSA-N C[C@](C(CO)O[C@@H]1COC(c2ccccc2)=O)([C@@H]1OC(c1ccccc1)=O)F Chemical compound C[C@](C(CO)O[C@@H]1COC(c2ccccc2)=O)([C@@H]1OC(c1ccccc1)=O)F MGQBJSHOIUJIFV-SEFOKTEQSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- -1 sulfuric acid Ester Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (6)
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CN201510632093.4A CN106554333B (zh) | 2015-09-29 | 2015-09-29 | 一种药物中间体的合成方法 |
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CN201510632093.4A CN106554333B (zh) | 2015-09-29 | 2015-09-29 | 一种药物中间体的合成方法 |
Publications (2)
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CN106554333A CN106554333A (zh) | 2017-04-05 |
CN106554333B true CN106554333B (zh) | 2018-11-30 |
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CN201510632093.4A Active CN106554333B (zh) | 2015-09-29 | 2015-09-29 | 一种药物中间体的合成方法 |
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Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107245064B (zh) * | 2017-05-19 | 2019-09-20 | 福安药业集团宁波天衡制药有限公司 | 索非布韦中间体的制备方法 |
CN107573304A (zh) * | 2017-09-27 | 2018-01-12 | 上海泓博智源医药股份有限公司 | 一种索菲布韦中间体的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1211274A1 (en) * | 2000-12-01 | 2002-06-05 | Canon Kabushiki Kaisha | Method for producing aliphatic polyester |
CN100475957C (zh) * | 2003-07-10 | 2009-04-08 | 三井化学株式会社 | 新型葡萄糖酸脱水酶 |
CN101600725A (zh) * | 2006-10-10 | 2009-12-09 | 法莫赛特股份有限公司 | 制备呋喃核糖基嘧啶核苷 |
-
2015
- 2015-09-29 CN CN201510632093.4A patent/CN106554333B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1211274A1 (en) * | 2000-12-01 | 2002-06-05 | Canon Kabushiki Kaisha | Method for producing aliphatic polyester |
CN100475957C (zh) * | 2003-07-10 | 2009-04-08 | 三井化学株式会社 | 新型葡萄糖酸脱水酶 |
CN101600725A (zh) * | 2006-10-10 | 2009-12-09 | 法莫赛特股份有限公司 | 制备呋喃核糖基嘧啶核苷 |
Non-Patent Citations (1)
Title |
---|
Discovery of a new PCC-mediated stereoselective oxidative spiroketalization process. An access to a new type of poly-THF spiroketal compound displaying anticancer activity;Vincenzo Piccialli,等;《Organic & Biomolecular Chemistry》;20090619;第7卷(第15期);第3038页图3 * |
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Effective date of registration: 20190510 Address after: 223800 Suqian Eco-chemical Science and Technology Industrial Park, Suqian City, Jiangsu Province Patentee after: Jiangsu Furui Kangtai Pharmaceutical Co.,Ltd. Address before: 210 042 32 blocks, 699-18 Xuanwu Avenue, Nanjing, Jiangsu Province Patentee before: JIANGSU FURUI BIOPHARMACEUTICAL CO.,LTD. |
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CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: No. 8, Zhongxing Road, Ecological Chemical Technology Industrial Park, Suqian City, Jiangsu Province, 223800 Patentee after: Jiangsu Alpha Group Furui Pharmaceutical (Suqian) Co.,Ltd. Address before: 223800 Suqian Eco-chemical Science and Technology Industrial Park, Suqian City, Jiangsu Province Patentee before: Jiangsu Furui Kangtai Pharmaceutical Co.,Ltd. |