US 11,939,323 B2
Methods of making a modulator of hemoglobin
Xiang Wang, South San Francisco, CA (US); Shinji Fujimori, San Francisco, CA (US); Todd Daniel Nelson, Cream Ridge, NJ (US); Ana Cristina Parra Rivera, Plainsboro, NJ (US); Devon Mundal, Seattle, WA (US); Benjamin Graetz, San Mateo, CA (US); and Morin M. Frick, San Mateo, CA (US)
Assigned to Global Blood Therapeutics, Inc., South San Francisco, CA (US)
Filed by Global Blood Therapeutics, Inc., South San Francisco, CA (US)
Filed on May 13, 2022, as Appl. No. 17/744,525.
Claims priority of provisional application 63/188,735, filed on May 14, 2021.
Prior Publication US 2022/0388996 A1, Dec. 8, 2022
Int. Cl. C07D 413/06 (2006.01)
CPC C07D 413/06 (2013.01) 19 Claims
 
1. A process for preparing a compound of formula I:

OG Complex Work Unit Chemistry
comprising:
(i) contacting a compound of formula 1:

OG Complex Work Unit Chemistry
wherein X1 is halo;
with a metalating reagent and carbon dioxide, wherein the metalating agent is a compound of formula X-M-R, and wherein M is a metal, R is an alkyl or aryl, and X is a halide or alkali metal, to form a compound of formula 2a:

OG Complex Work Unit Chemistry
(ii) contacting a compound of formula 2a with a compound of formula:
PG-X2
wherein PG is a hydroxy protecting group and X2 is halo;
to form a compound of formula 3:

OG Complex Work Unit Chemistry
(iii) contacting a compound of formula 3 with a compound of formula 4:

OG Complex Work Unit Chemistry
to form a compound of formula 5:

OG Complex Work Unit Chemistry
(iv) contacting a compound of formula 5 with a compound of formula 6:

OG Complex Work Unit Chemistry
to form a compound of formula 7:

OG Complex Work Unit Chemistry
and
(v) deprotecting a compound of formula 7 to form a compound of formula I.