US 12,441,745 B2
Processes and compounds
Michael Markey, Northborough, MA (US)
Assigned to RADIUS PHARMACEUTICALS, INC., Boston, MA (US)
Appl. No. 17/430,248
Filed by Radius Pharmaceuticals, Inc., Boston, MA (US)
PCT Filed Feb. 11, 2020, PCT No. PCT/US2020/017777
§ 371(c)(1), (2) Date Aug. 11, 2021,
PCT Pub. No. WO2020/167855, PCT Pub. Date Aug. 20, 2020.
Claims priority of provisional application 62/804,391, filed on Feb. 12, 2019.
Prior Publication US 2022/0162233 A1, May 26, 2022
Int. Cl. C07F 5/02 (2006.01); C07C 213/08 (2006.01); C07C 217/04 (2006.01); C07C 231/12 (2006.01); C07C 233/25 (2006.01); C07C 235/78 (2006.01); C07C 237/20 (2006.01)
CPC C07F 5/025 (2013.01) [C07C 213/08 (2013.01); C07C 217/04 (2013.01); C07C 231/12 (2013.01); C07C 233/25 (2013.01); C07C 235/78 (2013.01); C07C 237/20 (2013.01)] 16 Claims
 
1. A process of preparing a compound of formula (VIII)

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comprising the reduction of a compound of formula (VII)

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wherein said compound of formula (VII) is prepared by a reductive amination of a compound of formula (VI)

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in the presence of a compound of formula (f)

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wherein said compound of formula (VI) is prepared by contacting a compound of formula (V)

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with a chiral acid to form an enantiomerically enriched salt, crystallizing the enantiomerically enriched salt, and freeing the compound of formula (VI),
wherein said compound of formula (V) is prepared by treatment of a compound of formula (IV) with an acid, base, or reducing agent;

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wherein said compound of formula (IV) is prepared by reduction of a compound of formula (III)

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wherein said compound of formula (III) is prepared by the coupling of a compound of formula (I)

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with a compound of formula (II)

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and wherein P1 is H, or a phenol protecting group; Rb is H or Et; P2 is (C═O)—CH3; X is a halogen, transition metal or boron-containing compound; and X′ is a halogen, transition metal-containing function or boron-containing function; and wherein said X and X′ are suitable for cross-coupling of compound (I) with compound (II).