Back to results
US 12,590,089 B2Granted
Processes for preparing toll-like receptor modulator compounds
AssigneeGilead Sciences, Inc.
InventorsAndrea Ambrosi, Florence J. Bachrach, Pavel R. Badalov, Stephen P. Lathrop, Jeffrey E. Merit, Beau P. Pritchett, Christopher S. Regens, Tiago Vieira, Adam B. Weinstein, Todd A. Wenderski, Zehua Zheng
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods for preparing (R)-2-((2-amino-7-fluoropyrido[3,2-d]pyrimidin-4-yl)amino)-2-methylhexan-1-ol or a salt thereof and related key intermediates.
Claims7
A method for preparing a compound of Formula II:
- or a salt thereof, comprising:
- a) forming a first reaction mixture comprising a compound of Formula V:
- a compound having the Formula PG-NHC(═NH)NH2 or a salt thereof, a first transition-metal catalyst, a first base, and a first solvent to form the compound of Formula II, a salt thereof,
- wherein
- R1, R2, and R3 are each independently hydrogen, F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy;
- R4 is hydrogen or methyl;
- R5 is C3-6 alkyl;
- X is F, Cl, Br, I, or OTs;
- and
- PG is an amino protecting group.
7 more elements
A compound of Formula III:
- or a salt thereof, wherein
- R1, R2, and R3 are each independently hydrogen, F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy;
- R4 is hydrogen or methyl;
- R5 is C3-6 alkyl;
- and
- X is F, Cl, Br, I, or OTs.
3 more elements
A compound of Formula IV:
- or a salt thereof, wherein
- R1, R2, and R3 are each independently hydrogen, F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy;
- R4 is hydrogen or methyl;
- R5 is C3-6 alkyl;
- X is F, Cl, Br, I, or OTs;
- and
- AG1 is Cl, Br, OSO3H, OSO3−, OMs, OTs, or OTf.
4 more elements
A compound of Formula V:
- or a salt thereof, wherein
- R1, R2, and R3 are each independently hydrogen, F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy;
- R4 is hydrogen or methyl;
- R5 is C3-6 alkyl;
- and
- X is F, Cl, Br, I, or OTs,
- provided that the compound of Formula V is not
- 3-bromo-N-(1-hydroxy-3-methylbutan-2-yl)picolinamide,
- 3-bromo-N-(1-hydroxy-3,3-dimethylbutan-2-yl)picolinamide,
- 3-bromo-N-(1-hydroxy-4-methylpentan-2-yl)picolinamide,
- 3-bromo-N-(1-hydroxy-4-methylpentan-2-yl)picolinamide,
- 3,6-dichloro-N-(1-hydroxy-3-methylbutan-2-yl)picolinamide,
- 3,6-dichloro-N-(1-hydroxy-4-methylpentan-2-yl)picolinamide,
- 3,4,5-trichloro-N-(1-hydroxy-3-methylbutan-2-yl)picolinamide,
- 3,6-dichloro-N-(1-hydroxy-4,4-dimethylpentan-2-yl)picolinamide, or
- 3,4,5-trichloro-N-(1-hydroxy-4-methylpentan-2-yl)picolinamide.
13 more elements
A compound of Formula XII:
- or a salt thereof, wherein
- R1, R2, and R3 are each independently hydrogen, F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy;
- and
- R6 and R7 are each independently hydrogen, C1-4 alkyl, or C3-6 cycloalkyl, or
- R6 and R7 are combined to form a 3-6 membered N-linked heterocycloalkyl, optionally having an additional 1-2 heteroatoms selected from O and S,
- provided that at least one of R1, R2, and R3 is F, Cl, CN, CF3, C1-3 alkyl, or C1-3 alkoxy.
3 more elements
Dependencies are inferred from the claim text.