US 12,145,901 B1
Process for preparing tetralin compounds
Joel Worley Beatty, San Mateo, CA (US); Samuel Lawrie Drew, Millbrae, CA (US); Matthew Epplin, San Francisco, CA (US); Jeremy Fournier, Fremont, CA (US); Balint Gal, Hayward, CA (US); Karl T. Haelsig, Berkeley, CA (US); Clayton Hardman, San Francisco, CA (US); Jaroslaw Kalisiak, Newark, CA (US); Kenneth Victor Lawson, San Francisco, CA (US); Manmohan Reddy Leleti, Dublin, CA (US); Artur Karenovich Mailyan, Livermore, CA (US); Guillaume Mata, Berkeley, CA (US); Brandon Reid Rosen, San Mateo, CA (US); Zhang Wang, Foster City, CA (US); and Kai Yu, Hayward, CA (US)
Assigned to Arcus Biosciences, Inc., Hayward, CA (US)
Filed by ARCUS BIOSCIENCES, INC., Hayward, CA (US)
Filed on Sep. 16, 2022, as Appl. No. 17/932,688.
Claims priority of provisional application 63/245,287, filed on Sep. 17, 2021.
Int. Cl. C07C 317/32 (2006.01); B01J 23/46 (2006.01); B01J 31/18 (2006.01); B01J 31/22 (2006.01); C07C 315/04 (2006.01); C07C 317/14 (2006.01); C07D 317/72 (2006.01); C07F 7/12 (2006.01); C07F 7/16 (2006.01)
CPC C07C 317/32 (2013.01) [B01J 31/1805 (2013.01); B01J 31/2295 (2013.01); C07C 315/04 (2013.01); C07C 317/14 (2013.01); C07D 317/72 (2013.01); C07F 7/12 (2013.01); C07F 7/16 (2013.01); B01J 2231/643 (2013.01); B01J 2531/821 (2013.01); B01J 2531/824 (2013.01); C07C 2602/08 (2017.05); C07C 2602/10 (2017.05)] 25 Claims
OG exemplary drawing
 
1. A process:
comprising contacting a compound of Formula (IIa)

OG Complex Work Unit Chemistry
with a chiral ruthenium (II) catalyst and a hydrogen reagent;
thereby preparing a compound of Formula (Ia):

OG Complex Work Unit Chemistry
wherein
the chiral ruthenium (II) catalyst is RuCl(p-cymene)[(R,R)-Ts-DPEN];
R1 and R2 are independently selected from —H, —F, —Cl, and —CN;
R3 is —H, —F or —Cl;
R4 is selected from —H, —F, —Cl, —C1-C3 alkyl, and —S(O)2(C1-C3 alkyl), wherein the —C1-C3 alkyl or the —S(O)2(C1-C3 alkyl) is optionally substituted with 1-3 halogen atoms;
R5 is an alcohol protecting group; and
the compound of Formula (Ia) has at least 90% diastereomeric purity.