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US 11,976,053 B2Granted
Process of preparing a peptide epoxyketone immunoproteasome inhibitor, and precursors thereof
AssigneeKezar Life Sciences
InventorsHenry Johnson, Sean Dalziel, Dustin McMinn
Life of this patent
Estimating the term…
Abstract
Disclosed herein are methods for preparing [(2S,3R)—N—[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide (compound “G”): and precursors thereof.
Claims20
A method of preparing benzyl (2S,3R)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoate (compound “D”)
- comprising:
- (a) admixing a tertiary amine base and a suspension of:
- (i) (2S,3R)-1-(benzyloxy)-3-hydroxy-3-(4-methoxyphenyl)-1-oxopropan-2-aminium salt (compound “B”):
- wherein X− is a counterion;
- and
- (ii) (2-morpholinoacetyl)-L-alanine (compound “C”):
- in an aprotic solvent to form a mixture;
- and
- (b) admixing a coupling agent and the mixture of step (a) to form compound D;
- wherein the temperature of each admixing step is maintained at −5° C. to 5° C.
7 more elements
A crystalline compound selected from:
- (a) a crystalline form of (2S,3R)-1-(benzyloxy)-3-hydroxy-3-(4-methoxyphenyl)-1-oxopropan-2-aminium chloride salt (compound “B-Cl”)
- characterized by an X-ray powder diffraction pattern comprising peaks at 4.6, 9.2, 13.8, 18.5, and 32.9±0.2° 2θ using Cu Kα radiation,
- (b) a crystalline form of (2S,3R)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoic acid (compound “E”):
- characterized by an X-ray powder diffraction pattern comprising peaks at 6.2, 8.5, 9.7, 12.7, 13.7, 16.0, 16.9, 17.2, 18.4, 18.9, 19.2, 19.7, 22.5, 24.7, 25.4, 28.7, and 29.7±0.2° 2θ using Cu Kα radiation;
- and
- (c) a crystalline form of (S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-aminium salt (compound “F”):
- wherein X is tosylate,
- characterized by an X-ray powder diffraction pattern comprising peaks at 6.8, 7.1, 7.4, 20.3, 23.0, 23.6, 24.5, 29.3, and 31.2±0.2° 2θ using Cu Kα radiation.
5 more elements
Dependencies are inferred from the claim text.