US 12,435,049 B2
Synthesis of vinylic protected alcohol intermediates
Austin G. Smith, Cary, NC (US); and Liang Huang, Thousand Oaks, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US)
Appl. No. 17/918,607
Filed by AMGEN INC., Thousand Oaks, CA (US)
PCT Filed Apr. 27, 2021, PCT No. PCT/US2021/029271
§ 371(c)(1), (2) Date Oct. 13, 2022,
PCT Pub. No. WO2021/225823, PCT Pub. Date Nov. 11, 2021.
Claims priority of provisional application 63/020,862, filed on May 6, 2020.
Prior Publication US 2023/0174496 A1, Jun. 8, 2023
Int. Cl. C07D 267/12 (2006.01); C07D 267/18 (2006.01); C07D 513/04 (2006.01); C07D 513/10 (2006.01); C07D 519/00 (2006.01)
CPC C07D 267/18 (2013.01) [C07D 513/04 (2013.01); C07D 519/00 (2013.01)] 39 Claims
 
1. A process for synthesizing compound D:

OG Complex Work Unit Chemistry
comprising:
(a) admixing compound B, or a salt thereof, and compound C in an organic solvent to form a slurry, wherein the organic solvent is selected from the group consisting of a nonpolar aromatic solvent, an ether solvent, a chlorinated solvent, an alcohol solvent, acetonitrile, dimethylformamide (DMF), dimethylcarbonate, dimethylacetamide (DMAc), N-methylpyrrolidinone (NMP), and a combination thereof:

OG Complex Work Unit Chemistry
and
(b) admixing the slurry of step (a) and a reducing agent to form a mixture comprising compound D;
wherein:
OPG is an alcohol protecting group selected from the group consisting of an ether, an acetal or ketal, an acyl, a sulfonyl, and a silyl ether;
R1 is H or C1-6alkyl; and
R2 is a protected aldehyde.