US 11,807,651 B2
Process for the preparation of 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile
Charles Todd Eary, Stamford, CT (US); Stacey Spencer, Boulder, CO (US); Zack Crane, Longmont, CO (US); Katelyn Chando, Longmont, CO (US); Sylvie Asselin, Longmont, CO (US); Weidong Liu, Longmont, CO (US); Mike Welch, Longmont, CO (US); Adam Cook, Boulder, CO (US); Gabrielle R. Kolakowski, Boulder, CO (US); Andrew T. Metcalf, Boulder, CO (US); David A. Moreno, Boulder, CO (US); and Tony P. Tang, Boulder, CO (US)
Assigned to Loxo Oncology Inc., Indianapolis, IN (US); and Array BioPharma Inc., Boulder, CO (US)
Filed by Loxo Oncology, Inc., Indianapolis, IN (US); and Array BioPharma Inc., Boulder, CO (US)
Filed on Aug. 13, 2021, as Appl. No. 17/401,892.
Application 17/401,892 is a continuation of application No. 16/902,424, filed on Jun. 16, 2020, granted, now 11,098,064.
Application 16/902,424 is a continuation of application No. 16/156,955, filed on Oct. 10, 2018, granted, now 10,745,419, issued on Aug. 18, 2020.
Claims priority of provisional application 62/570,565, filed on Oct. 10, 2017.
Prior Publication US 2021/0380609 A1, Dec. 9, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 519/00 (2006.01); C07D 471/04 (2006.01)
CPC C07D 519/00 (2013.01) [C07D 471/04 (2013.01)] 11 Claims
 
1. A process for preparing a compound of Formula I

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein the process comprises the steps of:
a) treating a compound of formula 35

OG Complex Work Unit Chemistry
or a salt thereof with a first triflating reagent to form a compound of formula 36

OG Complex Work Unit Chemistry
or a salt thereof;
b) treating the compound of formula 36 or a salt thereof with a compound of formula

OG Complex Work Unit Chemistry
or a salt thereof, wherein X represents a halogen or a sulfonate and R6 represents a boronic acid or ester with the boron atom as the point of attachment to the pyridine ring of compound 12, in the presence of a third catalyst comprising a metal to form the compound of formula 13 or a salt thereof

OG Complex Work Unit Chemistry
c) treating a compound of formula 13 with a compound of formula 14

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or a salt thereof, wherein R1 is an amine protecting group, to form the compound of formula 15 or a salt thereof,

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d) treating compound 15 with a deprotecting agent to form the compound of formula 16 or a salt thereof

OG Complex Work Unit Chemistry
e) treating the compound of formula 16 or a salt thereof with 6-methoxynicotinaldehyde and a reducing agent to form the compound of Formula I or a pharmaceutically acceptable salt thereof.