Organic Process Research and Development p. 1897 - 1904 (2012)
Update date:2022-08-25
Topics:
Gillmore, Adam T.
Badland, Matthew
Crook, Clare L.
Castro, Nieves M.
Critcher, Douglas J.
Fussell, Steven J.
Jones, Katherine J.
Jones, Matthew C.
Kougoulos, Eleftherios
Mathew, Jinu S.
McMillan, Lynne
Pearce, John E.
Rawlinson, Fiona L.
Sherlock, Alexandra E.
Walton, Robert
Novel PARP inhibitor 1 is a promising new candidate for treatment of breast and ovarian cancer. A modified synthetic route to 1 has been developed and demonstrated on 7 kg scale. In order to scale up the synthesis to multikilogram scale, several synthetic challenges needed to be overcome. The key issues included significant thermal hazards present in a Leimgruber-Batcho indole synthesis, a low-yielding side-chain installation, a nonrobust Suzuki coupling and hydrogen cyanide generation during a reductive amination. In addition to these issues, changing from intravenous to oral delivery required a new salt form and therefore a new crystallization procedure. This contribution describes development work to solve these issues and scaling up of the new process in the pilot plant.
View MoreShanghai Sunwise Chemical Co., Ltd
website:http://www.sunwisechem.com
Contact:86-021-33883180
Address:Room 10E, Building G, Westlink Center, No. 2337 Gudai Road, Minhang District, Shanghai, China PC: 201100
Nanjing Qirui Material Co., Ltd.
Contact:+86-25-52320053
Address:F4-5, #17 Building, Chuang Yi Yuan, No.6 Guanghua East Street, Nanjing, 210007 P.R.China
Yangzhou Zhongbao Pharmaceutical Co.,Ltd
Contact:+86-514-88290838
Address:Jiangsu Baoying county economic develpment zone in baoying avenue91
Contact:+86-25-83719363
Address:106-7 Chunnan Rd, Chunxi Town, Gaochun, Nanjing, China
Sichuan Mianzhu Ronghong Chemical Co.,LTd
Contact:8613981840544
Address:XINSHI INDUSTRY PARK,MIANZHU,SICHUAN,CHINA
Doi:10.1021/op050044y
(2005)Doi:10.1021/jacs.9b00341
(2019)Doi:10.1016/S0040-4039(00)70378-9
(1965)Doi:10.1039/c9nj02727k
(2019)Doi:10.1021/jacs.9b02505
(2019)Doi:10.1002/cplu.201500282
(2015)