US 12,391,725 B2
Method for production of novel galeterone analogs and uses thereof
Vincent C. O. Njar, Glen Burnie, MD (US); Purushottamachar Puranik, Gaithersburg, MD (US); and Francis Murigi, Germantown, MD (US)
Assigned to NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT, Bethesda, MD (US)
Appl. No. 16/310,000
Filed by Vincent C. O. Njar, Glen Burnie, MD (US); Purushottamachar Puranik, Gaithersburg, MD (US); and Francis Murigi, Germantown, MD (US)
PCT Filed Jun. 22, 2017, PCT No. PCT/US2017/038765
§ 371(c)(1), (2) Date Dec. 14, 2018,
PCT Pub. No. WO2017/223320, PCT Pub. Date Dec. 28, 2017.
Claims priority of provisional application 62/353,103, filed on Jun. 22, 2016.
Prior Publication US 2019/0169227 A1, Jun. 6, 2019
Int. Cl. C07J 75/00 (2006.01); A61K 31/58 (2006.01); C07J 43/00 (2006.01); A61P 35/00 (2006.01)
CPC C07J 43/003 (2013.01) [A61K 31/58 (2013.01); A61P 35/00 (2018.01)] 7 Claims
 
1. A process for preparing 3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2) and 3α-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (5), the process comprising:
a first reaction comprising reacting a compound having Formula 1 (1)

OG Complex Work Unit Chemistry
to produce 3-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (7, 8); and
a second reaction comprising reacting the 3-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (7, 8) to produce 3-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2, 5),
wherein:
the first reaction comprises mesylation of the compound having Formula 1 (1) to produce a mesylate (4), and azidation of the mesylate (4) comprising contacting the mesylate (4) with (i) an alkali metal azide to produce 3α-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (7) or (ii) an organic azide to produce 3β-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (8), wherein the 3α-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (7) is produced in a yield of at least 60% with a standard deviation of 2%, and the 3β-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (8) is produced in a yield of at least 93% with a standard deviation of 2%, and
the second reaction comprises reduction of the 3α-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (7) and 3β-azido-17-(1H-benzimidazole-1-yl) androsta-5,16-diene (8) to produce an α-amine (9) and a β-amine (10), and cyclization of the α-amine (9) and β-amine (10) to produce the 3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (2) and 3α-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (5).