- Patent Title: Process for the preparation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide and salts thereof
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Application No.: US16302312Application Date: 2017-05-18
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Publication No.: US11214571B2Publication Date: 2022-01-04
- Inventor: Mark Reynolds , Charles Todd Eary , Stacey Spencer , Derrick Juengst , Bruno Hache , Yutong Jiang , Julia Haas , Steven W. Andrews
- Applicant: Array BioPharma Inc. , Loxo Oncology, Inc.
- Applicant Address: US CO Boulder; US CT Stamford
- Assignee: Array BioPharma Inc.,Loxo Oncology, Inc.
- Current Assignee: Array BioPharma Inc.,Loxo Oncology, Inc.
- Current Assignee Address: US CO Boulder; US CT Stamford
- Agency: Meunier Carlin & Curfman LLC
- International Application: PCT/US2017/033257 WO 20170518
- International Announcement: WO2017/201241 WO 20171123
- Main IPC: C07D487/04
- IPC: C07D487/04
![Process for the preparation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide and salts thereof](/abs-image/US/2022/01/04/US11214571B2/abs.jpg.150x150.jpg)
Abstract:
Process for preparing (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)—N—((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent. (S)—N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, is a tyrosin kinase (TRK) inhibitor for trearing e.g. cancer.
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