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Floxuridine Synthesis
| Content Provider | The Lens |
|---|---|
| Description | La présente invention concerne un procédé de préparation de floxuridine, ledit procédé consiste à faire réagir un composé de formule Ia avec un composé de formule IIa en présence d'un acide Al pour obtenir un composé de formule IIIa sous forme pratiquement pure sur le plan diastéréoisomère. La floxuridine, selon l'invention peut être utilisée en tant que médicament anticancéreux. La floxuridine peut également être utile dans la préparation d'autres médicaments anticancéreux, par exemple NUC-3373. |
| Abstract | The present invention relates to a process for the preparation of floxuridine, said process comprising reacting a compound of Formula la with a compound of Formula lla in the presence of an acid Al to provide a compound of Formula Ilia in substantially diastereomerically pure form. Floxuridine may be useful as an anti-cancer drug. Floxuridine may also be useful in the preparation of other anti-cancer drugs, e.g. NUC-3373. |
| Related Links | https://www.lens.org/lens/patent/012-173-387-224-122/frontpage |
| Language | English |
| Publisher Date | 2019-03-21 |
| Access Restriction | Open |
| Alternative Title | Synthèse De Floxuridine |
| Content Type | Text |
| Resource Type | Patent |
| Date Applied | 2018-09-18 |
| Agent | Hgf Limited |
| Applicant | Nucana Plc |
| Application No. | 2018052662 |
| Claim | A process for the preparation of FUDR in substantially diastereoisomerically pure form: the process comprising step a) and optionally step b): a) reacting a compound of Formula la with a compound of Formula Ma in the presence of an acid A1 to provide a compound of Formula Ilia in substantially diastereomerically pure form: wherein R 1 and R 2 are each independently trialkylsilyl groups; R 3 and R 4 are each independently selected from H and a protecting group; and X is a leaving group; b) where R 3 and/or R 4 are protecting groups, optionally removing the protecting group R 3 and/or R 4 from the compound of formula Ilia to provide FUDR in substantially diastereomerically pure form; wherein the step of reacting a compound of Formula la with a compound of Formula lla is carried out at a temperature T1 in the range from 9 °C to 15 °C. a) reacting a compound of Formula la with a compound of Formula lla in the presence of an acid A1 to provide a compound of Formula Ilia in substantially diastereomerically pure form: b) where R 3 and/or R 4 are protecting groups, optionally removing the protecting group R 3 and/or R 4 from the compound of formula Ilia to provide FUDR in substantially diastereomerically pure form; wherein the acid A1 is selected from a Lewis acid, a sulfonic acid and a carboxylic acid. A process of claim 1 or claim 2, wherein the step of reacting a compound of Formula la with a compound of Formula Ma is carried out in a solvent S1 selected from acetonitrile (ACN), 1 ,2-dichloroethane (DCE) and dichloromethane (DCM). wherein R 1 and R 2 are each independently trialkylsilyl groups; R 3 and R 4 are each independently selected from H and a protecting group; and X is a leaving group; b) where R 3 and/or R 4 are protecting groups, optionally removing the protecting group R 3 and/or R 4 from the compound of formula Ilia to provide FUDR in substantially diastereomerically pure form; wherein the step of reacting a compound of Formula la with a compound of Formula Ma is carried out in a solvent S1 selected from acetonitrile (ACN), 1 ,2-dichloroethane (DCE) and dichloromethane (DCM). A process of 2 or claim 4, wherein the step of reacting a compound of Formula la with a compound of Formula Ma is carried out at a temperature T1 that is below room temperature. A process of claim 5, wherein T1 is below 20 °C. A process of claim 5 or claim 6, wherein T1 is in the range from 9 °C to 15 °C. A process of claim 1 or claim 4, wherein the acid A1 is selected from a Lewis acid, a sulfonic acid and a carboxylic acid. A process of any preceding claim, wherein the acid is a sulfonic acid. A process of claim 9, wherein the acid is p-toluenesulfonic acid. 1 1 . A process of any preceding claim, wherein the step of reacting a compound of Formula la with a compound of Formula Ma is carried out in a solvent S1 that is dichloromethane (DCM). A process of any preceding claim, wherein R 1 and R 2 are each trimethylsily A process of any preceding claim, wherein R 3 and R 4 are each a 4- chlorobenzoyl group. A process of claim 10, wherein R 3 and R 4 are removed using methanolic ammonia solution. A process of any preceding claim, wherein X is CI. A process of any preceding claim, wherein the process further comprises -3373: NUC-3373 A process of claim 16, wherein the FUDR is converted to NUC-3373 in a process comprising step d) and optionally comprising steps c) and e): c) optionally converting FUDR to a compound of formula Va in which R 6 is a protecting group; d) reacting a compound of Formula IVa; with a compound of Formula Va in presence of a base (B2) to provide a compound of Formula Via; wherein R 5 is a leaving group and R 6 is independently selected from H (in which case the compound Formula IVa Formi Formula Via e) where R 6 is a protecting group, optionally removing the protecting group R 1 from the compound of formula Via to provide NUC-3373. FUDR obtainable using the process of any one of claims 1 to 15. NUC-3373 obtainable using the process of claim 16 or claim 17. |
| CPC Classification | SUGARS;DERIVATIVES THEREOF;NUCLEOSIDES;NUCLEOTIDES;NUCLEIC ACIDS |
| Extended Family | 066-096-879-881-041 174-560-432-859-763 187-696-250-220-023 159-629-336-525-527 101-089-176-663-373 180-827-478-762-542 012-173-387-224-122 068-718-111-676-936 |
| Patent ID | 2019053476 |
| Inventor/Author | Kotala Mani Dammalapati Venkata |
| IPC | C07H1/00 C07H19/073 |
| Status | Pending |
| Simple Family | 066-096-879-881-041 187-696-250-220-023 174-560-432-859-763 159-629-336-525-527 101-089-176-663-373 180-827-478-762-542 012-173-387-224-122 068-718-111-676-936 |
| CPC (with Group) | C07H1/00 C07H19/073 C07H19/06 C07H19/10 |
| Issuing Authority | United States Patent and Trademark Office (USPTO) |
| Kind | Patent Application Publication |
