JP2018536640A5 - - Google Patents
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- Publication number
- JP2018536640A5 JP2018536640A5 JP2018519936A JP2018519936A JP2018536640A5 JP 2018536640 A5 JP2018536640 A5 JP 2018536640A5 JP 2018519936 A JP2018519936 A JP 2018519936A JP 2018519936 A JP2018519936 A JP 2018519936A JP 2018536640 A5 JP2018536640 A5 JP 2018536640A5
- Authority
- JP
- Japan
- Prior art keywords
- ibrutinib
- compound
- reaction mixture
- amorphous
- isolated
- 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.)
- Pending
Links
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 56
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims description 56
- 229960001507 ibrutinib Drugs 0.000 claims description 56
- 150000001875 compounds Chemical class 0.000 claims description 36
- 239000011541 reaction mixture Substances 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- 238000005917 acylation reaction Methods 0.000 claims description 16
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 13
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 12
- 150000007529 inorganic bases Chemical class 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 8
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- -1 Compound (S) -3-hydroxypiperidine hydrochloride Chemical class 0.000 claims description 5
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 9
- 239000003960 organic solvent Substances 0.000 claims 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 239000007787 solid Substances 0.000 claims 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 239000002904 solvent Substances 0.000 claims 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 239000008346 aqueous phase Substances 0.000 claims 2
- 239000003125 aqueous solvent Substances 0.000 claims 2
- 238000001035 drying Methods 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 2
- 239000012456 homogeneous solution Substances 0.000 claims 2
- 239000011261 inert gas Substances 0.000 claims 2
- 239000012074 organic phase Substances 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
- 238000005406 washing Methods 0.000 claims 2
- VLECDMDGMKPUSK-JEDNCBNOSA-N (3s)-piperidin-3-ol;hydrochloride Chemical compound Cl.O[C@H]1CCCNC1 VLECDMDGMKPUSK-JEDNCBNOSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 239000012298 atmosphere Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000012071 phase Substances 0.000 claims 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims 1
- 238000010926 purge Methods 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- YYVUOZULIDAKRN-UHFFFAOYSA-N Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[nH]2)c2ncn1 Chemical compound Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[nH]2)c2ncn1 YYVUOZULIDAKRN-UHFFFAOYSA-N 0.000 description 2
- GPSQYTDPBDNDGI-UHFFFAOYSA-N Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[n]2C3CNCCC3)c2ncn1 Chemical compound Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[n]2C3CNCCC3)c2ncn1 GPSQYTDPBDNDGI-UHFFFAOYSA-N 0.000 description 1
- GPSQYTDPBDNDGI-MRXNPFEDSA-N Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[n]2[C@H]3CNCCC3)c2ncn1 Chemical compound Nc1c(c(-c(cc2)ccc2Oc2ccccc2)n[n]2[C@H]3CNCCC3)c2ncn1 GPSQYTDPBDNDGI-MRXNPFEDSA-N 0.000 description 1
- PBTYRDMHPNDRSR-YFKPBYRVSA-N O[C@@H](CCC1)CN1C(C(F)(F)F)=O Chemical compound O[C@@H](CCC1)CN1C(C(F)(F)F)=O PBTYRDMHPNDRSR-YFKPBYRVSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562285035P | 2015-10-28 | 2015-10-28 | |
| US62/285,035 | 2015-10-28 | ||
| PCT/SG2016/050528 WO2017074265A1 (en) | 2015-10-28 | 2016-10-28 | Process for preparing ibrutinib and its intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018536640A JP2018536640A (ja) | 2018-12-13 |
| JP2018536640A5 true JP2018536640A5 (enExample) | 2019-12-05 |
Family
ID=58630729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018519936A Pending JP2018536640A (ja) | 2015-10-28 | 2016-10-28 | イブルチニブ及びその中間体の製造方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9834561B2 (enExample) |
| EP (1) | EP3368537A4 (enExample) |
| JP (1) | JP2018536640A (enExample) |
| KR (1) | KR20180063339A (enExample) |
| CN (1) | CN108349980A (enExample) |
| TW (1) | TWI642671B (enExample) |
| WO (1) | WO2017074265A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106279284A (zh) * | 2016-08-08 | 2017-01-04 | 上海孚璞生物科技有限公司 | 三取代膦亚胺类化合物及其制备方法、用途 |
| WO2019070698A1 (en) * | 2017-10-02 | 2019-04-11 | Johnson Matthey Public Limited Company | Novel forms of ibrutinib |
| CN111004239B (zh) * | 2018-10-08 | 2022-09-13 | 上海柏狮生物科技有限公司 | 一种依替鲁尼的前体制备方法 |
| CN113135917A (zh) * | 2020-01-16 | 2021-07-20 | 北京赛思源生物医药技术有限公司 | 一种依鲁替尼的无定型物及其药用组合物 |
| CN114105991A (zh) * | 2020-08-31 | 2022-03-01 | 北京四环制药有限公司 | 一种伊布替尼中间体的制备方法 |
| CN114105990A (zh) * | 2020-08-31 | 2022-03-01 | 北京四环制药有限公司 | 一种伊布替尼的合成方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014595A (zh) * | 2004-08-11 | 2007-08-08 | 杏林制药株式会社 | 新型环状氨基苯甲酸衍生物 |
| EP2526934B1 (en) | 2006-09-22 | 2015-12-09 | Pharmacyclics LLC | Inhibitors of bruton's tyrosine kinase |
| EA201492082A1 (ru) * | 2012-06-04 | 2015-03-31 | Фармасайкликс, Инк. | Кристаллические формы ингибитора тирозинкиназы брутона |
| CN103121999A (zh) | 2012-08-29 | 2013-05-29 | 苏州迪飞医药科技有限公司 | 一种酪氨酸激酶抑制剂pci-32765的合成方法 |
| US9156847B2 (en) | 2013-03-15 | 2015-10-13 | Janssen Pharmaceutica Nv | Processes and intermediates for preparing a medicament |
| CN105452257B (zh) * | 2013-08-12 | 2017-09-05 | 大鹏药品工业株式会社 | 新型稠合嘧啶化合物或其盐 |
| CN103626774B (zh) | 2013-11-20 | 2015-11-04 | 苏州明锐医药科技有限公司 | 伊鲁替尼的制备方法 |
| US9884869B2 (en) | 2014-03-27 | 2018-02-06 | Perrigo Api Ltd. | Ibrutinib solid forms and production process therefor |
| CN103965201A (zh) * | 2014-04-30 | 2014-08-06 | 淮海工学院 | 一种合成依鲁替尼中间体4-氨基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-d]嘧啶的方法 |
| US10266535B2 (en) | 2015-01-21 | 2019-04-23 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Inhibitor of FLT3 kinase and use thereof |
| CN104557945B (zh) * | 2015-01-27 | 2017-08-04 | 安润医药科技（苏州）有限公司 | 依鲁替尼合成方法 |
| CN105985343A (zh) * | 2015-02-12 | 2016-10-05 | 上海昶朗医药科技有限公司 | 伊布替尼的制备方法 |
| WO2016127915A1 (zh) * | 2015-02-12 | 2016-08-18 | 上海度德医药科技有限公司 | 伊布替尼的制备方法 |
| CN106188062A (zh) * | 2015-05-08 | 2016-12-07 | 苏州鹏旭医药科技有限公司 | 依鲁替尼的制备方法、依鲁替尼的中间体及中间体的制备方法 |
-
2016
- 2016-10-27 TW TW105134856A patent/TWI642671B/zh active
- 2016-10-27 US US15/336,418 patent/US9834561B2/en active Active
- 2016-10-28 CN CN201680063300.1A patent/CN108349980A/zh active Pending
- 2016-10-28 KR KR1020187014718A patent/KR20180063339A/ko not_active Withdrawn
- 2016-10-28 EP EP16860399.1A patent/EP3368537A4/en not_active Withdrawn
- 2016-10-28 WO PCT/SG2016/050528 patent/WO2017074265A1/en not_active Ceased
- 2016-10-28 JP JP2018519936A patent/JP2018536640A/ja active Pending
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